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Acromegaly Treatment Industry 2019 Global Market Size, Demand, Growth Prospects, Key Insights, Top Companies and Forecast till 2025 – VaporBlash

The global Acromegaly Treatment market is driven by the growing prevalence of the genetic disease, changing lifestyle. Also, factors such as rising incidence of hormonal diseases, such as hypopituitarism and endocrine diseases, and high demand for the advanced treatment is expected to increase the demand for Acromegaly treatment market.

Factors, such as unavailability of precise treatment and high cost of the surgery can restrain the market growth.

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Some of the key players operating in this market include Pfizer Inc., Chiasma Inc., Novartis AG, Ipsen Biopharmaceuticals Inc., Wockhardt Ltd., Troikaa Pharmaceuticals Limited, GlaxoSmithKline plc, Aegis Therapeutics LLC, Crinetics Pharmaceuticals Inc, Daewoong Pharmaceutical Co Ltd, Peptron Inc, among others.

Increasing government support, favorable government insurance policies and schemes for the patients and rapid developments in technology will offer lucrative opportunities.

Based on Application, the Acromegaly Treatment market is segmented into Hospitals, Clinics, and others.

Based on Disease Types, the Acromegaly Treatment market is segmented into Ectopic Acromegaly, Pseudo Acromegaly.

Regionally, North America was the largest revenue generator in the Acromegaly Treatment market in 2017, because of high investments in research and development activities to investigate the applications of Acromegaly Treatment market.

Key Benefits of the Report:

* Global, Regional, Country, Application, and Disease Types Market Size and Forecast from 2014-2025

* Detailed market dynamics, industry outlook with market specific PESTLE, Value Chain, Supply Chain, and SWOT Analysis to better understand the market and build strategies

* Identification of key companies that can influence this market on a global and regional scale

* Expert interviews and their insights on market shift, current and future outlook and factors impacting vendors short term and long term strategies

* Detailed insights on emerging regions, Application& Disease Types, and competitive landscape with qualitative and quantitative information and facts.

Global Acromegaly Treatment Industry 2019 Market Research Report is spread across 121 pages and provides exclusive vital statistics, data, information, trends and competitive landscape details in this niche sector.

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Target Audience:

* Acromegaly Treatment providers

* Traders, Importer and Exporter

* Raw material suppliers and distributors

* Research and consulting firms

* Government and research organizations

* Associations and industry bodies.

Research Methodology

The Market is derived through extensive use of secondary, primary, in-house research followed by expert validation and third party perspective like analyst report of investment banks. The secondary research forms the base of our study where we conducted extensive data mining, referring to verified data sources such as government and regulatory published materials, technical journals, trade magazines, and paid data sources.

For forecasting, regional demand & supply factor, investment, Market dynamics including technical scenario, consumer behavior, and end use industry trends and dynamics , capacity Production, spending were taken into consideration.

We have assigned weights to these parameters and quantified their Market impacts using the weighted average analysis to derive the expected Market growth rate.

The Market estimates and forecasts have been verified through exhaustive primary research with the Key Industry Participants (KIPs) which typically include:

* Original Manufacturer,

* Application Supplier,

* Distributors,

* Government Body & Associations, and

* Research Institute.

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Table Of Content

1 Executive Summary

2 Methodology And Market Scope

3 Acromegaly Treatment Market Industry Outlook

4 Acromegaly Treatment Market Type Outlook

5 Acromegaly Treatment Market Application Outlook

6 Acromegaly Treatment Market Regional Outlook

7 Competitive Landscape

End Of The Report

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Acromegaly Treatment Industry 2019 Global Market Size, Demand, Growth Prospects, Key Insights, Top Companies and Forecast till 2025 - VaporBlash

Alopecia Market Outlook and Opportunities in Grooming Regions with Forecast to 2027 | CAPILLUS, Sun Pharmaceutical Industries, Cipla, Merck and Co,…

Alopecia is a medical term, which is generally used for hair loss. It is a common autoimmune disorder that often results in unpredictable hair loss, which can lead to complete loss of hair on the scalp or, in uttermost cases, the entire body. This extreme condition can affect anyone irrespective of gender and age. Medications such as Minoxidil or Rogaine are the topical agents that are used for the treatment of disease. Other treatments of alopecia include medications that are sometimes used for other autoimmune disorders.

The alopecia market is anticipated to grow in the forecast, owing to the increasing prevalence of alopecia areata and Rise in incidence of chronic disorders such as, cancer, polycystic ovary syndrome (PCOS), hyperthyroidism, hypothyroidism, acute stress disorder, hypopituitarism, lupus. However, the rising awareness among people about hair loss is likely to add novel opportunities in the forecast period.

Top Companies Covered in this Report:1. CAPILLUS, 2. Sun Pharmaceutical Industries Ltd., 3. Cipla Inc., 4. Merck and Co., Inc., 5. Transitions Hair, 6. Follica, Inc., 7. Johnson and Johnson Services, Inc., 8. Concert Pharmaceuticals, 9. HCell Inc., 10. GlaxoSmithKline plc.

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The Global Alopecia Market Analysis to 2027 is a specialized and in-depth study of the healthcare IT industry with a special focus on the global market trend analysis. The report aims to provide an overview of Alopecia market with detailed market segmentation by service type, age group, and geography. The global Alopecia market is expected to witness high growth during the forecast period. The report provides key statistics on the market status of the leading Alopecia market players and offers key trends and opportunities in the market.

The global alopecia market is segmented on the basis of disease type, drug type, route of administration and distribution channel. Based on disease type, the market is classified as, alopecia areata, androgenic alopecia, alopecia totalis, ciatricial alopecia and traction alopecia. Based on the drug type, the market is segmented into minoxidil, finasteride and other drug types. On the basis of route of administration, the market is categorized as oral, topical and injectable. Based on the distribution channel, the market is segmented as hospitals, retail pharmacies and online pharmacies.

The report analyzes factors affecting Alopecia market from both demand and supply side and further evaluates market dynamics effecting the market during the forecast period i.e., drivers, restraints, opportunities, and future trend. The report also provides exhaustive PEST analysis for all five regions namely; North America, Europe, APAC, MEA and South & Central America after evaluating political, economic, social and technological factors effecting the Alopecia market in these regions.

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Fundamentals of Table of Content:

1 Report Overview1.1 Study Scope1.2 Key Market Segments1.3 Players Covered1.4 Market Analysis by Type1.5 Market by Application1.6 Study Objectives1.7 Years Considered

2 Global Growth Trends2.1 Alopecia Market Size2.2 Alopecia Growth Trends by Regions2.3 Industry Trends

3 Market Share by Key Players3.1 Alopecia Market Size by Manufacturers3.2 Alopecia Key Players Head office and Area Served3.3 Key Players Alopecia Product/Solution/Service3.4 Date of Enter into Alopecia Market3.5 Mergers & Acquisitions, Expansion Plans

4 Breakdown Data by Product4.1 Global Alopecia Sales by Product4.2 Global Alopecia Revenue by Product4.3 Alopecia Price by Product

5 Breakdown Data by End User5.1 Overview5.2 Global Alopecia Breakdown Data by End User

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Alopecia Market Outlook and Opportunities in Grooming Regions with Forecast to 2027 | CAPILLUS, Sun Pharmaceutical Industries, Cipla, Merck and Co,...

Bristol-Myers Squibb Announces Update on CheckMate -915 for Opdivo (nivolumab) Plus Yervoy (ipilimumab) Versus Opdivo Alone in Patients with Resected…

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced results for one of the co-primary endpoints from CheckMate -915, a randomized Phase 3 study evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) versus Opdivo alone for the adjuvant treatment of patients who have had a complete surgical removal of stage IIIb/c/d or stage IV (no evidence of disease) melanoma. A statistically significant benefit was not reached for the co-primary endpoint of recurrence-free survival (RFS) in patients whose tumors expressed PD-L1 <1%. The Data Monitoring Committee recommended that the study continue unchanged. The study remains double-blinded and will continue to assess the other co-primary endpoint of RFS in the all-comer (intent-to-treat) population.

About CheckMate -915CheckMate -915 is a Phase 3, randomized, placebo controlled, double-blind study evaluating Opdivo in combination with Yervoy versus Opdivo monotherapy, an approved standard of care, in patients who have had a complete surgical removal of stage IIIb/c/d or stage IV (no evidence of disease) melanoma. Patients enrolled in the trial had no prior anti-cancer treatment for melanoma, except surgery for the melanoma lesion(s) and/or adjuvant radiation therapy after neurosurgical resection for central nervous system lesions. The trial randomized 1,943 patients to receive either Opdivo 240 mg intravenously every two weeks and Yervoy 1 mg/kg every six weeks or Opdivo 480 mg every four weeks for one year.

About MelanomaMelanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 91,270 new diagnoses of melanoma and more than 9,320 related deaths are estimated for 2018. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanoma is mostly curable when treated in its very early stages; however, survival rates are roughly halved if regional lymph nodes are involved. Patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and a 10-year survival of 10% to 15%.

Adjuvant Therapy in MelanomaMelanoma is separated into five staging categories (Stages 0- IV) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes.

Stage III melanoma has generally reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized) and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy. Despite surgical intervention, most patients experience disease recurrence and progress to metastatic disease.

Stage IV melanoma occurs when the melanoma has spread beyond the original site and regional lymph nodes to more distant areas of the body. The most common sites of metastasis are to vital organs, soft tissues and distant lymph nodes.

Bristol-Myers Squibb: Advancing Oncology ResearchAt Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

About OpdivoOpdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the bodys own immune system to help restore anti-tumor immune response. By harnessing the bodys own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivos leading global development program is based on Bristol-Myers Squibbs scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Companys Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVOOPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

About Yervoy

Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types.

Indications and Important Safety Information for YERVOY (ipilimumab)

Indications

YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older).

YERVOY (ipilimumab) is indicated for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy, and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7% (2/119) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of 7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis occurred in 13% (51/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 8% (10/119) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barr syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypophysitis occurred in 9% (36/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hypophysitis occurred in 3.4% (4/119) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal insufficiency occurred in 5% (21/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 5.9% (7/119) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving this dose of OPDIVO with YERVOY. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism occurred in 12% (66/547) of patients receiving this dose of OPDIVO with YERVOY. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 15% (18/119) of patients. Hyperthyroidism occurred in 12% (14/119) of patients. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 1.7% (2/119) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash occurred in 22.6% (92/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16% (90/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 14% (17/119) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg (0.2%) after 1.7 months of exposure. Encephalitis occurred in one RCC patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after approximately 4 months of exposure. Encephalitis occurred in one MSI-H/dMMR mCRC patient (0.8%) receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg after 15 days of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barr syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.

If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate study in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 4.2% (5/119) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1 receptor blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1 receptor blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue breastfeeding during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in 2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 032, serious adverse reactions occurred in 45% of patients receiving OPDIVO (n=245). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, pneumonitis, pleural effusions, and dehydration. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in 2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43% of patients receiving sunitinib. The most frequent serious adverse reactions reported in 2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis; in patients treated with sunitinib, they were pneumonia, pleural effusion, and dyspnea. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in 1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY, serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in 2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in 2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO-treated patients.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 017 and 057, the most common adverse reactions (20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 032, the most common adverse reactions (20%) in patients receiving OPDIVO (n=245) were fatigue (45%), decreased appetite (27%), musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation (20%), and cough (20%). In Checkmate 025, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 214, the most common adverse reactions (20%) reported in patients treated with OPDIVO plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58% vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28% vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), decreased appetite (21% vs 29%), dyspnea (20% vs 21%), and vomiting (20% vs 28%). In Checkmate 205 and 039, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (10%) in patients receiving OPDIVO (n=236) were cough and dyspnea at a higher incidence than investigators choice. In Checkmate 275, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the most common adverse reactions (20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY, the most common adverse reactions (20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 238, the most common adverse reactions (20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

Checkmate Trials and Patient PopulationsCheckmate 037previously treated metastatic melanoma; Checkmate 066previously untreated metastatic melanoma; Checkmate 067previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032small cell lung cancer; Checkmate 025previously treated renal cell carcinoma; Checkmate 214previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039classical Hodgkin lymphoma; Checkmate 141recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275urothelial carcinoma; Checkmate 142MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040hepatocellular carcinoma; Checkmate 238adjuvant treatment of melanoma.

About the Bristol-Myers Squibb and Ono Pharmaceutical CollaborationIn 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers SquibbBristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Cautionary Statement Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, the possibility of unfavorable results from further clinical trials involving the combination treatment described in this release and whether such product candidate for the additional indications described in this release will be successfully developed and commercialized. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol-Myers Squibbs business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol-Myers Squibbs Annual Report on Form 10-K for the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol-Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

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Bristol-Myers Squibb Announces Update on CheckMate -915 for Opdivo (nivolumab) Plus Yervoy (ipilimumab) Versus Opdivo Alone in Patients with Resected...

Look inside the old Natwest in Prescot after its total transformation – Liverpool Echo

A former Natwest Bank in Prescot has undergone an unrecognisable transformation - and will now offer a vital service to the community.

Six years ago, mum-of-four Debbie O'Brien, from Huyton, struggled to find a day centre where her daughter Jodie could socialise and her complex needs would be met.

Jodie, 25, has multiple health needs, including cerebral palsy, severe learning developmental delay, encephalitis, Lennox Gastuat syndrome, short-term memory loss, cirrhosis, kyphosis, osteoporosis, hypopituitarism, edema and a rare disease called panhypopituitarism.

Fearful her daughter was becoming isolated, Debbie decided to set up her own club for adults and their families in Kirkby .

Through Al's Club, Debbie met fellow-mum Andrea Evans, originally from Halewood , who attended with her son Callam James Jones, 29.

Callam, who has autism, has defied the odds through his life, having a double heart bypass, kidney failure and now being 5 years in remission.

Forming a close bond and wanting to make a change, the pair teamed up to offer a bespoke service for adults aged 18 and over with disabilities and complex medical needs.

Transforming the former Natwest Bank on Eccleston Street in Prescot , Al's Activity Respite Centre (Arc) officially launched in the town this week - and the response has been overwhelming.

Director Andrea Evans, 51, said: "My son Callam, he's the one who inspires me more than anyone else in the world.

"I'm so glad that we've done this.

"It hasn't been easy because I've juggled my own job, but I knew what the end goal would be and it's going to be an absolute honour working alongside Debbie.

"Years ago adults with disabilities were told that they had to fit into society.

"We're here to re-educate society and our guys are going to be told they no longer need to try and fit in.

"They are the community, they are society and there is no reason on this earth why they shouldn't be valued and accepted."

Al's Arc offers everything from an aromatherapy room and sensory room to a mini gym, a variety of activity sessions and more.

The space is also available for other community groups to use in the evenings, as well as having subletting offices upstairs.

Founder Debbie O'Brien, 47, said: "I do know and I do believe that the two of us together are going to transform adult services for the better.

"We want our members out in the community doing what we do, they're just going to have some guidance and support.

"Everyone has given up their time to help us with this project.

"We've had a team of different tradesman in and the transformation to us has been huge."

Al's Arc received dozens of donations and support from neighbours, local businesses and Knowsley Council - as well as help from family-friend Graham in completing the buildings transformation.

The pair said they also received emotional support from others in the community, including Social Growth Officer Jacqui Meadows and Eileen from Breast Mates, a local support group who will also be utilising the space.

Andrea said: "This is a dream come true. This is our children's future and their children's future and this is all about saying disability belongs.

"We're not in competition with any other disability service. We are going to be enabling every single day and if we can enable any other services to promote themselves and be more successful then that's what we'll do."

John Maddox, operations manager at Structec N.W. Limited said: "Much of the work that we do in Knowsley is centred around adaptations to the homes of people with disabilities, so we were delighted when Debbie invited us to get involved and provide some help to get this wonderful facility off the ground.

"The passion of those at the heart of this much needed community project is truly inspirational and will make Al's Arc a huge success."

Follow Jess on Twitter here

You can read more of her stories here

Email her onjessica.molyneux@reachplc.com

Or contact Jess on Facebook if you want to share any news, stories or updates.

Keep up to date with the latest breaking newshere

Like theECHO Facebook pageand follow@livechonewson Twitter

Cllr Sean Donnelly, Cabinet Member for Health and Social Care, said: Im delighted that Als Arc has opened its doors in Prescot, providing much-needed services here in the borough.

"The services they are offering will really benefit young adults in Knowsley, helping them to develop their skills, confidence and independent living.

"This is a great example of Knowsley Better Together in action seeing people and organisations coming together for the benefit of Knowsley and its residents. I wish them well and look forward to visiting.

For more information email: thearcprescot@gmail.com

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Look inside the old Natwest in Prescot after its total transformation - Liverpool Echo

PRACTICALLY ACTIVE: Love your liver and it will love you back – Arkansas Democrat-Gazette

The cruise director is the ship's liver because almost everything you can think of filters through them at some point.

Actor Willie Aames

October is Liver Awareness Month, the month chosen by the American Liver Foundation to raise public awareness of the importance of liver health.

As a diabetic, I see the importance, even though I'm not really sure what the old workhorse does.

Diabetes Education Online, the website of the Diabetes Teaching Center at the University of California, San Francisco states that the liver acts as the body's glucose (or fuel) reservoir and helps keep circulating blood sugar levels and other body fuels steady and constant. It stores and manufactures glucose, depending on the body's need.

The need to store or release glucose is primarily signaled by the hormones insulin and glucagon.

During a meal, the liver will store sugar or glucose as glycogen for a later time when your body needs it. When you are not eating, especially overnight or between meals, the body has to make its own sugar. The liver supplies sugar or glucose by turning glycogen into glucose in a process called glycogenolysis.

The liver can also manufacture the needed glucose by harvesting amino acids, waste products and fat byproducts. That process is gluconeogensis.

The liver also makes another fuel, ketones, when sugar is in short supply. When glycogen storage is running low, the body starts to conserve sugar supplies for organs that always require sugar. They include the brain, red blood cells and parts of the kidney. That process is called ketogenesis.

Ketones are burned as fuel by muscles and other body organs, and the sugar is saved for the organs that need it.

When you have diabetes, these bodily processes can be thrown off balance. Everything affects everything.

More and more these days I see the term fatty liver disease, but there is also nonalcoholic fatty liver disease. According to the website of the Mayo Clinic (mayoclinic.org), NAFLD is an umbrella term for a range of liver conditions affecting people who drink little to no alcohol. The main characteristic is too much fat stored in liver cells.

They say it is increasingly common around the world, especially in Western nations. In the United States, it is the most common form of chronic liver disease, affecting about one-quarter of the population.

Some people with nonalcoholic fatty liver disease can develop nonalcoholic steatohepatitis, an aggressive form of fatty liver disease marked by liver inflammation. It can progress to advanced scarring (cirrhosis) and liver failure. The damage is similar to the damage caused by heavy alcohol use.

There are usually no real signs or symptoms, but when any do appear, they can include fatigue, and pain or discomfort in the upper right abdomen.

Possible signs of this steatohepatitis include abdominal swelling, enlarged blood vessels just beneath the skin's surface, an enlarged spleen, red palms and yellowing of the skin and eyes.

There seems to be limited understanding of why some people accumulate fat in the liver and others do not. And there is also limited understanding of why some fatty livers develop inflammation that progresses to cirrhosis. But both conditions are linked to the following:

Overweight or obesity.

Insulin resistance, in which cells don't take up sugar in response to the hormone insulin.

High blood sugar (hyperglycemia), indicating prediabetes or Type 2 diabetes.

High levels of fats, particularly trigylcerides, in the blood.

A wide range of diseases and conditions can increase the risk too. They include high cholesterol, polycystic ovary syndrome, sleep apnea, underactive thyroid (hypothyroidism) and underactive pituitary gland (hypopituitarism).

Those at risk include older people, Type 2 diabetics and people with body fat concentrated in the abdomen.

The condition is a bit scary. Have a frank talk with your doctor if any of this seems familiar to you.

Email me at:

rboggs@arkansasonline.com

Style on 10/07/2019

Originally posted here:
PRACTICALLY ACTIVE: Love your liver and it will love you back - Arkansas Democrat-Gazette

Male Hypogonadism Market Growth Opportunities and Dynamic Business by 2025 – NewsStoner

Global Male Hypogonadism Market: Snapshot

Hypogonadism in males refers to a condition in the male body where the testes show a significantly reduced level of functioning than normal. The overall result of male hypogonadism is a reduction in the rate of biosynthesis of male sex hormones. This state is more commonly known as interrupted stage 1 puberty. Hypoandrogenism, or the low androgen or testosterone level in a male can vary in severity from person to person. It is often the cause of partial or complete infertility. There are multiple forms of male hypogonadism and even more ways to classify them. Most endocrinologists commonly classify male hypogonadism on the basis of the level of defectiveness of the male reproductive system.

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In many cases, doctors also measure the level of gonadotropins to classify a patient between primary and secondary male hypogonadism. Primary male hypogonadism refers to the cause of the condition being due to defective gonads. There are different types of primary male hypogonadism, including Turner syndrome and Klinefelter syndrome. Secondary male hypogonadism is caused by defects in pituitary or hypothalamic glands. They include Kallmann syndrome and hypopituitarism.

Global Male Hypogonadism Market: Overview

Male Hypogonadism refers to a clinical condition, wherein the testes fail to produce enough testosterone leading to delayed puberty or incomplete development. The condition is related to impaired development of muscle mass, development of breast tissues, impaired body hair growth, and lack of deepening of the voice.

The male Hypogonadism market can be segmented by therapy, type, drug delivery, and geography.

The report presents an in-depth analysis of the global male hypogonadism market with current trends and future estimates to explain the imminent investment pockets. The quantitative analysis of the market for the forecast period from 2017 to 2025 will enable stakeholders to capitalize on the prevailing growth opportunities.

Global Male Hypogonadism Market: Trends and Opportunities

The top driver of the male hypogonadism market includes rising prevalence of testosterone deficiency among men, increasing infertility rates, and increasing awareness among individuals about hypogonadism treatment due to awareness drives organized by several governments across the world. Moreover, high risk of hypogonadism among the geriatric population with obesity and diabetes, and increasing prevalence of chronic disorders among the geriatrics are further expected to boost the markets growth.

However, factors such as high side effects of testosterone products are challenging the growth of testosterone replacement therapy market. Top players in the market are focused on research and development to introduce newer products with fewer or negligible side effects and improved results. For example, LPCN 1111, a product which is under development from Lipocine Inc., is a newer testosterone prodrug that utilizes Lipral technology for enhanced systemic absorption and for enhanced solubility of testosterone. Nevertheless, technological advancements are anticipated to extend new opportunities to the markets growth.

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Global Male Hypogonadism Market: Regional Overview

The global male Hypogonadism market can be analyzed with respect to the regional segments of North America, Asia Pacific, Europe, Latin America, and the Middle East and Africa. North America held the majority share of the global market in the recent past and is expected to retain its dominant position in the near future. This is mainly due to the rise in the number of individuals suffering from primary and secondary conditions of hypogonadism, and rising awareness among individuals about treatment options for the condition. Moreover, the presence of ultra-modern healthcare infrastructure and increasing popularity of technologically advanced products are expected to offer new opportunities for top players in this market. The region is closely followed by Europe.

Asia Pacific is expected to offer lucrative opportunities to this market due to the modernization of the healthcare infrastructure in the emerging economies of India and China and the increasing awareness about the treatment for the condition. In Asia Pacific, the increasing prevalence of hypogonadism and infertility rates along with the rising geriatric population base with diabetes and obesity are propelling the growth of this market. China, Taiwan, and Malaysia are some of the countries that display the highest rate of male hypogonadism.

Major Companies Mentioned in Report

Some of the key players in the male Hypogonadism market include AbbVie Inc., Astrazeneca plc, Eli Lilly and Company Ltd., Merck & Co. Inc., SA, Finox Biotech, Laboratories Genevrier, Teva Pharmaceutical Industries Ltd., Allergan plc, Bayer AG, Endo International plc, IBSA Institut Biochimque, and Ferring.

Key players are focused on product approval for growth considerations and to cater to the changing demand of the industry. The introduction of innovative and technologically advanced products is also the focus of key players to increase their market share and for serving patients in a better manner.

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Male Hypogonadism Market Growth Opportunities and Dynamic Business by 2025 - NewsStoner

What causes prolonged menstrual bleeding? – The New Times

Dear Doctor,

My period usually lasts longer than a week, however, this month, it has gone beyond that. I have had it for over two weeks now and the bleeding is heavier than usual. This is accompanied by dizziness and nausea. Is this something I should worry about?

Lyna

Dear Lyna,

What is your age currently? A woman having normal regular menstrual cycles previously can have irregular cycles around menopause. This happens because the balance of hormones governing the menstrual cycles changes at this age. Actual cessation of menses occurs some time later around 50 years of age, some years sooner or later. But the changes start from around 40 years or so. This is manifested in the form of irregular periods with scanty or prolonged and heavy bleeding.

Though this change in menstrual cycles is normal, if recurrent or persistent, it is a cause for concern.

Excess bleeding due to menopause is diagnosed clinically and by investigations to exclude other causes of prolonged bleeding. Treatment is by hormonal therapy. But at this age, it is necessary to weigh the advantage of hormonal therapy, versus the potential harm caused due to its side effects like clotting, hypertension, heart problems, and et cetera. Iron supplements are given if anaemia occurs. In severe cases, the uterus is removed surgically.

Heavy and or prolonged bleeding can be due to uterine fibroids. Fibroid is benign tumour that develops in the inner lining of uterus and can be small or big in size, single or multiple in number. Apart from heavy and or prolonged menstrual bleeding, they can cause lower abdominal pain, discomfort and backache. Fibroids are easily diagnosed by ultrasound. Treatment is by hormones or surgery.

Excess and or prolonged bleeding during menses can be due to other hormonal disorders. Hyperthyroidism, i.e. excess amount of hormones released by thyroid gland is one of them. This can occur at any age. Other manifestations of hyperthyroidism like excess sweating, tremulousness of hands, increased appetite, altered bowel movements, to mention a few, may be present or absent, along with excess menstrual bleeding. Hyperthyroidism is easily diagnosed by a simple blood test and is treatable. Hypopituitarism, adrenal gland disorders are other endocrine ailments, which can cause prolonged menstrual bleeding. These disorders are also easily diagnosed and are treatable.

Excess menstrual bleeding can be a side effect of anti-clotting drugs like aspirin and clopidrogel. Some women may develop it as a manifestation of inherent bleeding disorders.

Heavy and or prolonged bleeding mostly results in chronic anaemia, i.e., deficiency of necessary amount of haemoglobin (component of blood that carries oxygen to the body cells). This manifests as early fatigue, joint pain, palpitations and breathlessness on exertion. Over time, chronic anaemia puts strain over the heart resulting in heart failure. This is prevented by treating heavy bleeding during periods. Treatment depends on the cause.

Dr. Rachna Pande is a specialist in internal medicine.

More here:
What causes prolonged menstrual bleeding? - The New Times

CHMP Adopts Positive Opinion for BAVENCIO (avelumab) Plus Axitinib for First-Line Treatment of Patients with Advanced Renal Cell Carcinoma -…

ROCKLAND, MA and NEW YORK, US, September 20, 2019 /PRNewswire/ -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of BAVENCIO (avelumab) in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). The opinion was based on positive findings from the Phase III JAVELIN Renal 101 study, which demonstrated a significant extension in median progression-free survival (PFS) and a clinically meaningful improvement in objective response rate (ORR) for the combination across all prognostic risk groups compared with sunitinib.1 The CHMP positive opinion will be reviewed by the European Commission (EC), with a decision anticipated in the fourth quarter of this year. EMD Serono and Pfizer have a global strategic alliance to jointly develop and commercialize BAVENCIO.

"Today's positive CHMP opinion is a significant step toward potentially transforming the treatment landscape and bringing much needed options to people living with advanced renal cell carcinoma in Europe. We believe that the combination of BAVENCIO plus axitinib has the potential to help address a significant need for patients with advanced renal cell carcinoma for first-line treatments with a benefit across all prognostic risk groups, and we look forward to a decision from the European Commission," said Luciano Rossetti, Head of Global R&D for EMD Serono.

In 2018, an estimated 136,500 new cases of kidney cancer were diagnosed in Europe, and approximately 54,700 people died from the disease.2 RCC is the most common form of kidney cancer, accounting for about 3% of all cancers in adults.2 Approximately 20% to 30% of patients are first diagnosed with RCC at the advanced stage, and 30% of patients treated for an earlier stage go on to develop metastases.3,4 About half of patients living with advanced RCC do not go on to receive additional treatment after first-line therapy,5,6for reasons that may include poor performance status oradverse events from their initial treatment.5,7,8The five-year survival rate for patients with metastatic RCC is approximately 12%.9

"Kidney cancer represents a significant burden in Europe, where incidence rates are among the highest in the world," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Pfizer has been a leader in the development of kidney cancer treatments for more than a decade, and it is a privilege to continue our efforts to bring a new treatment option to this community."

The U.S. Food and Drug Administration (FDA) approved BAVENCIO in combination with axitinib for the first-line treatment of patients with advanced RCC in May 2019.10 Asupplemental application for BAVENCIO in combination with axitinib in unresectable or metastatic RCC was submitted inJapanin January 2019.

About the JAVELIN Renal 101 Study

The Phase III JAVELIN Renal 101 study is a randomized, multicenter, open-label study of BAVENCIO in combination with axitinib in 886 patients with untreated advanced or metastatic RCC. The major efficacy outcome measures were PFSas assessed by a Blinded Independent Central Review (BICR) using RECIST v1.1 and overall survival (OS) in the first-line treatment of patients with advanced RCC who have PD-L1-positive tumors (PDL1 expression level 1%). If PFS was statistically significant in patients with PD-L1-positive tumors, it was then tested in all patients irrespective of PD-L1 expression. PFS based on BICR assessment per RECIST v1.1 and OS irrespective of PDL1 expression, objective response, time to response (TTR), duration of response (DOR) and safety are included as secondary endpoints. The study is continuing for OS.

About the JAVELIN Clinical Development Program

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 10,000 patients evaluated across more than 15 different tumor types. In addition to RCC, these tumor types include gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer and urothelial carcinoma.

About BAVENCIO (avelumab)

BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.11-13 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.13-15 In November 2014, EMD Serono and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indication in the US

BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

BAVENCIO Important Safety Information from the US FDA-Approved Label

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade 3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barr syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACEoccurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

Please see full US Prescribing Information and Medication Guide available at http://www.BAVENCIO.com.

Axitinib Important Safety Information from the US FDA-Approved Label

Hypertension including hypertensive crisis has been observed with axitinib. Blood pressure should be well controlled prior to initiating axitinib. Monitor for hypertension and treat as needed. For persistent hypertension, despite use of antihypertensive medications, reduce the dose. Discontinue axitinib if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of axitinib, and discontinuation should be considered if there is evidence of hypertensive crisis.

Arterial and venous thrombotic events have been observed with axitinib and can be fatal. Use with caution in patients who are at increased risk or who have a history of these events.

Hemorrhagic events, including fatal events, have been reported with axitinib. Axitinib has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the axitinib dose.

Cardiac failure has been observed with axitinib and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with axitinib. Management of cardiac failure may require permanent discontinuation of axitinib.

Gastrointestinal perforation and fistula, including death, have occurred with axitinib. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment.

Hypothyroidism requiring thyroid hormone replacement has been reported with axitinib. Monitor thyroid function before initiation of, and periodically throughout, treatment.

No formal studies of the effect of axitinib on wound healing have been conducted. Stop axitinib at least 24 hours prior to scheduled surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed with axitinib. If signs or symptoms occur, permanently discontinue treatment.

Proteinuria has been observed with axitinib. Monitor for proteinuria before initiation of, and periodically throughout, treatment with axitinib. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment.

Liver enzyme elevation has been observed during treatment with axitinib. Monitor ALT, AST, and bilirubin before initiation of, and periodically throughout, treatment.

For patients with moderate hepatic impairment, the starting dose should be decreased. Axitinib has not been studied in patients with severe hepatic impairment.

Axitinib can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception during treatment.

Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided.

Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers.

Please see full Prescribing Information for axitinib.

ADVERSE REACTIONS (BAVENCIO + AXITINIB)

Fatal adverse reactionsoccurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions(all grades, 20%) in patients with advanced RCC receiving BAVENCIO in combination with axitinib(vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities(all grades, 20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib(vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

The most common adverse reactions (all grades, 20%)in patients with advanced RCC receiving BAVENCIO in combination with axitinib(vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades,20%)worsening from baselinein patients with advanced RCC receiving BAVENCIO in combination with axitinib(vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

About Merck KGaA, Darmstadt, Germany-Pfizer Alliance

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germanyand Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germanyand Pfizer enables the companies to benefit from each other's strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to http://www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

About EMD Serono, Inc.

EMD Serono - the biopharmaceutical business of Merck KGaA, Darmstadt,Germany, in the U.S. andCanada- is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations based in the company's home state ofMassachusetts.www.emdserono.com.

About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across healthcare, life science and performance materials. Around 52,000 employees work to make a positive difference to millions of people's lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices the company is everywhere. In 2018, Merck KGaA, Darmstadt, Germany, generated sales of 14.8 billion in 66 countries.

The company holds the global rights to the name and trademark "Merck" internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA, Darmstadt, Germany operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials. Since its founding 1668, scientific exploration and responsible entrepreneurship have been key to the company's technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.

Pfizer Inc.: Breakthroughs that change patients' lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at http://www.pfizer.com.In addition, to learn more, please visit us on http://www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

Pfizer Disclosure Notice

The information contained in this release is as of September 20, 2019. Pfizer assumes no obligation to update forward-looking statementscontained in this release as the result of new information or future events or developments.

This release contains forward-looking information about BAVENCIO (avelumab), including a potential new indication in the European Union for BAVENCIO in combination with axitinib for the treatment of patients with advanced renal cell carcinoma, the alliance between MerckKGaA, Darmstadt, Germany, and Pfizer involving BAVENCIO and clinical development plans, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BAVENCIO and axitinib; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data and uncertainties regarding whether the other primary endpoint of JAVELIN Renal 101 will be met; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and whenany drug applications may be filed for BAVENCIO in combination with axitinib in any other jurisdictions or in any jurisdictions for any other potential indications for BAVENCIO or combination therapies; whether and when the pending applications in the European Union and Japan for BAVENCIO in combination with axitinib may be approved and whether and when regulatory authorities in any jurisdictions where any other applications are pending or may be submitted for BAVENCIO or combination therapies, including BAVENCIO in combination with axitinib may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy, and, if approved, whether they will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of BAVENCIO or combination therapies, including BAVENCIO in combination with axitinib; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2018, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at http://www.sec.gov and http://www.pfizer.com.

References

Your Contacts EMD Serono Inc. Media Gangolf Schrimpf +49 6151 72 9591 Investor Relations +49 6151 72 3321

Pfizer Inc., New York, USA Media Jessica Smith +1 212 733 6213 Investor Relations Ryan Crowe +1 212 733 8160

SOURCE EMD Serono

Excerpt from:
CHMP Adopts Positive Opinion for BAVENCIO (avelumab) Plus Axitinib for First-Line Treatment of Patients with Advanced Renal Cell Carcinoma -...

Pfizer Presents Scientific Advancements in Cancer Care at the ESMO Congress 2019 Highlighting Expanded Portfolio – Yahoo Finance

Presentations of interest include a late-breaking abstract on expanded Phase 3 data in BRAF-mutant metastatic colorectal cancer

Pfizer Inc. (NYSE:PFE) is presenting data across its industry-leading oncology portfolio, including company-sponsored and collaborative research studies, spanning 11 therapies in 22 types of cancer, at the European Society for Medical Oncology (ESMO) Congress to be held in Barcelona, Spain, September 27 - October 1, 2019. Data from nearly 50 abstracts involving Pfizer cancer medicines will illustrate the diversity of the portfolio and the companys cutting-edge scientific approach. For the first time, this will include data presentations on compounds from the acquisition of Array Biopharma Inc.

At this years ESMO Congress, were looking forward to showcasing how were embodying ESMOs theme of translating science into better patient care, said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. Whether its studying patient populations such as those affected by BRAF-mutant metastatic colorectal cancer who are in need of new treatment options, utilizing new techniques like real-world evidence to understand further the impact of our medicines in the non-clinical trial setting, or studying a different way to administer a treatment that may be more convenient for patients, Pfizer is leading the way in taking innovative approaches to meeting the needs of people living with cancer.

Clinical data can be complex and often difficult to understand if a person is not a scientist. To help interested non-scientists better understand the latest research, Pfizer developed summaries in non-technical language for research results being presented at this years ESMO Congress. These informational materials, called abstract plain language summaries (APLS), will be made available for non-scientists to learn more about Pfizers latest scientific developments.

Key Pfizer-sponsored abstracts leveraging the depth of Pfizers scientific advances include:

Details for key Pfizer-sponsored oral presentations, poster discussions and poster presentations are below:

In Europe, BAVENCIO (avelumab)is indicated as monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC).

BAVENCIO Important Safety Information from the U.S. FDA-Approved Label

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade 3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barr syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

Please see full U.S. Prescribing Information and Medication Guide for BAVENCIO available at http://www.Bavencio.com.

About INLYTA (axitinib)

In Europe, INLYTA (axitinib) is indicated for the treatment of adult patients with advanced renal-cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.

In the U.S., INLYTA is indicated for the treatment of advanced RCC after failure of one prior systemic therapy.

INLYTA Important Safety Information from the U.S. FDA-Approved Label

Hypertension including hypertensive crisis has been observed with axitinib. Blood pressure should be well controlled prior to initiating axitinib. Monitor for hypertension and treat as needed. For persistent hypertension, despite use of antihypertensive medications, reduce the dose. Discontinue axitinib if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of axitinib, and discontinuation should be considered if there is evidence of hypertensive crisis.

Arterial and venous thrombotic events have been observed with axitinib and can be fatal. Use with caution in patients who are at increased risk or who have a history of these events.

Hemorrhagic events, including fatal events, have been reported with axitinib. Axitinib has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the axitinib dose.

Cardiac failure has been observed with axitinib and can be fatal. Monitor for signs or symptoms of cardiac failure throughout treatment with axitinib. Management of cardiac failure may require permanent discontinuation of axitinib.

Gastrointestinal perforation and fistula, including death, have occurred with axitinib. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment.

Hypothyroidism requiring thyroid hormone replacement has been reported with axitinib. Monitor thyroid function before initiation of, and periodically throughout, treatment.

No formal studies of the effect of axitinib on wound healing have been conducted. Stop axitinib at least 24 hours prior to scheduled surgery.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed with axitinib. If signs or symptoms occur, permanently discontinue treatment.

Proteinuria has been observed with axitinib. Monitor for proteinuria before initiation of, and periodically throughout, treatment with axitinib. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment.

Liver enzyme elevation has been observed during treatment with axitinib. Monitor ALT, AST, and bilirubin before initiation of, and periodically throughout, treatment.

For patients with moderate hepatic impairment, the starting dose should be decreased. axitinib has not been studied in patients with severe hepatic impairment.

Axitinib can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception during treatment.

Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided.

Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers.

Please see full U.S. Prescribing Information for INLYTA at http://www.Inlyta.com.

About IBRANCE (palbociclib)

In Europe, IBRANCE (palbociclib) is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor; in combination with fulvestrant in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone releasing hormone agonist.

In the U.S., IBRANCE (palbociclib) 125 mg capsules is indicated for the treatment of adult patients with HR+/HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men; or fulvestrant in patients with disease progression following endocrine therapy.

IBRANCE Important Safety Information from the U.S. FDA-Approved Label

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade 3 adverse reactions (5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade 3 adverse reactions (5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

Please see full U.S. Prescribing Information for IBRANCE at http://www.Ibrance.com.

About XTANDI (enzalutamide)

In Europe, XTANDI (enzalutamide) is indicated for the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC); the treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated; the treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.

In the U.S., XTANDI is indicated for the treatment of patients with CRPC.

XTANDI Important Safety Information from the U.S. FDA-Approved Label

Warnings and Precautions

Seizure occurred in 0.4% of patients receiving XTANDI in clinical studies. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. Patients in the study had one or more of the following pre-disposing factors: use of medications that may lower the seizure threshold; history of traumatic brain or head injury, cerebrovascular accident or transient ischemic attack, Alzheimer's disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post-approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%). Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus 0.5% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures In the placebo-controlled clinical studies, falls occurred in 10% of patients treated with XTANDI compared to 4% of patients treated with placebo. Fractures occurred in 8% of patients treated with XTANDI and in 3% of patients treated with placebo. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

Embryo-Fetal Toxicity Safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI. XTANDI should not be handled by females who are or may become pregnant.

Adverse Reactions

The most common adverse reactions ( 10%) that occurred more frequently ( 2% over placebo) in the XTANDI patients from the randomized placebo-controlled trials were asthenia/fatigue, decreased appetite, hot flush, arthralgia, dizziness/vertigo, hypertension, headache and weight decreased. In the bicalutamide-controlled study, the most common adverse reactions ( 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In the placebo-controlled study of metastatic CRPC (mCRPC) patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-nave mCRPC patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the placebo-controlled study of non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse reactions were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an adverse event as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients. In the bicalutamide-controlled study of chemotherapy-nave mCRPC patients, Grade 3-4 adverse reactions were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials in patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In the placebo-controlled trial in patients with nmCRPC, Grade 1-4 neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4) and in 5% of patients receiving placebo (0.2% Grade 3-4).

Hypertension: In the two placebo-controlled trials in patients with mCRPC, hypertension was reported in 11% of XTANDI patients and 4% of placebo patients. Hypertension led to study discontinuation in <1% of patients in each arm. In the placebo-controlled trial in patients with nmCRPC, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see full U.S. Prescribing Information for XTANDI at http://www.Xtandi.com.

About LORBRENA (lorlatinib)

In Europe, LORBRENA (lorlatinib) is marketed as LORVIQUA and is indicated as monotherapy for the treatment of adult patients with ALK-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI.

In the U.S., LORBRENA is indicated for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

LORBRENA Important Safety Information from the U.S. FDA-Approved Label

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA. Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume at the same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA. Eighty percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 21 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 295 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1% experienced AV block and 0.3% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis. Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The most common (20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea; the most common (20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers and strong CYP3A inhibitors. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the LORBRENA dose as recommended. Concomitant use of LORBRENA decreases the concentration of CYP3A substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of LORBRENA has not been established for patients with severe renal impairment.

Please see full U.S. Prescribing Information for LORBRENA at http://www.Lorbrena.com.

About BRAFTOVI (encorafenib) and MEKTOVI (binimetinib)

In Europe, BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation.

In the U.S., BRAFTOVI and MEKTOVI are indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.

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Pfizer Presents Scientific Advancements in Cancer Care at the ESMO Congress 2019 Highlighting Expanded Portfolio - Yahoo Finance

Acute Hypopituitarism: Overview, Diagnostic Considerations …

Adrenocorticotropic hormone deficiency

A deficiency of adrenocorticotropic hormone (ACTH), or corticotropin, is characterized by a decrease in adrenal androgens and production of cortisol. Acute loss of adrenal function is a medical emergency and may lead to hypotension and death if not treated.

Signs and symptoms of ACTH deficiency may be profound and potentially fatal; they include myalgias, arthralgias, fatigue, headache, weight loss, anorexia, nausea, vomiting, abdominal pain, altered mentation or altered consciousness, dry wrinkled skin, decreased axillary and pubic hair, anemia of chronic disease, dilutional hyponatremia, hypoglycemia, hypotension, and shock.

Symptoms are nearly identical to those of primary adrenal insufficiency but can be differentiated by lack of hyperpigmentation. Hyperpigmentation occurs in a long feedback loop in which a cortisol deficiency results in increased production of ACTH by the pituitary. The ACTH precursor coupled to melanocyte-stimulating hormone is not produced in patients with pituitary disease, and therefore, hyperpigmentation does not take place.

Patients with secondary adrenal insufficiency usually are eukalemic. This differs from primary adrenal insufficiency, in which patients develop hyponatremia and hyperkalemia. Aldosterone secretion is not affected, as it does not depend on corticotropin but instead on the renin-angiotensin axis.

Secondary hypothyroidism due to decreased TSH (also known as thyrotropin) exhibits symptoms identical to those of primary thyroid disease, only typically less severe. Signs and symptoms of secondary hypothyroidism include fatigue, weakness, weight gain, thickened subcutaneous tissues, constipation, cold intolerance, altered mental status, impaired memory, and anemia. Physical examination of the patient may reveal bradycardia, delayed relaxation of the deep tendon reflexes, and periorbital edema.

Low levels of the gonadotropins--follicle-stimulating hormone (FSH) and luteinizing hormone (LH) --increase the risk of osteoporosis due to decreased bone density and result in hypogonadism in men and women. In men, symptoms include decreased libido, varying degrees of erectile dysfunction, decreased ejaculate, muscle weakness, and fatigue. Men with long-standing hypogonadism have decreased hair growth, soft testes, and gynecomastia.

Patients may be anemic due to decreased erythropoietin production, which causes a normochromic, normocytic anemia. Pubic and axillary hair growth is usually normal unless a concomitant ACTH deficiency exists.

Premenopausal women present with altered menstrual function, ranging from regular anovulatory periods to amenorrhea, as well as hot flashes, decreased libido, breast atrophy, vaginal dryness, and dyspareunia. Postmenopausal women usually present with headache or visual abnormalities due to other hormonal deficiencies or mass lesions.

In children, FSH and LH deficiency can cause eunuchoidism and lack of sexual development. FSH and LH have an indirect effect on bone growth by causing closure of the epiphysis. Characteristics of eunuchoidism are due to delay in closure of the epiphysis, resulting in long extremities.

In children, growth hormone (GH) deficiency presents as growth retardation and delayed sexual maturation. Patients may present with fasting hypoglycemia due to loss of the gluconeogenic effect of GH, which counteracts the effect of insulin. In adults, GH deficiency presents as weakness, poor wound healing, decreased exercise tolerance, and decreased social functioning.

Tumor growth that decreases prolactin (PRL) production affects the process of lactation; these tumors become evident only in the postpartum state. PRL deficiency is very rare; any process that affects the hypothalamus and the pituitary stalk decreases the normal inhibitory effect of dopamine from the hypothalamus on the pituitary, causing a rebound increase in PRL.

Antidiuretic hormone (ADH) deficiency causes polyuria and polydipsia (diabetes insipidus). When deficient in ADH (also known as vasopressin), the distal tubules of the kidney are unable to absorb water, producing very dilute urine and increasing serum osmolality. If water excretion exceeds oral intake, a patient may become hypotensive and hypovolemic, with hypernatremia and elevated serum osmolality. If fluid intake matches fluid output, serum sodium and osmolality may remain normal.

Central diabetes insipidus is caused by a decrease in ADH secretion, in contrast to nephrogenic diabetes insipidus, in which the kidney is ADH resistant.

Deficiency in oxytocin is characterized by a decrease in milk ejection during lactation. Interestingly, women with known oxytocin deficiency undergo normal labor and delivery despite the lack of hormone. One of the initial clues to the presence of Sheehan syndrome should be the lack of lactation secondary to oxytocin deficiency.

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Acute Hypopituitarism: Overview, Diagnostic Considerations ...

Hypopituitarism | Endocrinology | Dartmouth-Hitchcock

Alternative names: Pituitary Insufficiency

What is hypopituitarism? What are the signs of hypopituitarism? What causes hypopituitarism? How does my doctor tell if I have hypopituitarism? How is hypopituitarism treated?

Hypopituitarism is a condition in which the pituitary gland is not producing one or more of its hormones, or is producing them at lower than normal levels. These hormones stimulate other endocrine glands to produce their hormones. For example, if the pituitary gland doesn't make thyroid stimulating hormone (TSH), the thyroid gland doesn't work correctly.

Hypopituitarism is a rare disorder.

The symptoms of hypopituitarism depend on which hormones are being under-produced by the pituitary gland:

Hypopituitarism is often caused by an abnormal growth, or tumor, on the pituitary gland. Most pituitary tumors are benign (non-cancerous), and are called adenomas.

Damage to the pituitary gland can also cause hypopituitarism. Such damage can be caused by head injuries, radiation treatment for cancer, autoimmune disorders, a stroke, infections, and disease.

Diseases of the hypothalamus, the part of the brain located just above the pituitary, can also cause hypopituitarism.

Your doctor may recommend one or more of the following tests to diagnose hypopituitarism:

If hypopituitarism is caused by a pituitary tumor, treatment is aimed at removing the tumor, or reducing its effects. This can include medication, surgery, and/or radiation therapy.

Pituitary hormone replacement therapy is often required after successful treatment of a pituitary tumor.

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Hypopituitarism | Endocrinology | Dartmouth-Hitchcock

Hypopituitarism | Johns Hopkins Medicine

What is hypopituitarism?Hypopituitarism happens when your pituitary gland is not active enough. The front lobe of the gland may only partly work. Or it may not work at all. As a result the gland does not make enough hormones.What causes hypopituitarism?

Causes of hypopituitarism can directly affect the pituitary gland. Or they can indirectly affect the glandthrough changes inthe hypothalamus. Direct causes are:

Indirect causes are:

Symptoms are different for each person. They happen over time or right away. They depend on which hormones the pituitary gland is not making enough of. The following are common symptoms linked to certain hormones:

These symptoms may look like other health problems. Always see your health care provider for a diagnosis.

Your health care provider will ask about your past health. You will also need an exam. Other tests you may need:

Your health care provider will figure out the best treatment for you based on:

Treatment of hypopituitarism depends on what is causing it. The goal of treatment is have the pituitary gland work as it should. Treatment may include:

See the rest here:
Hypopituitarism | Johns Hopkins Medicine

Hypopituitarism Symptoms & Causes | Boston Children’s Hospital

We understand that you may have a lot of questions when your child is diagnosed with hypopituitarism. Is it dangerous? Will it affect my child long term? What do we do next? Weve tried to provide some answers to those questions on this site, and our experts can explain your childs condition fully.

Growth hormone is a protein produced by the pituitary gland, which is located near the base of the brain and attached to the hypothalamus (a part of the brain that helps to regulate the pituitary gland). If the pituitary gland or the hypothalamus is malformed or damaged, it may mean that the pituitary gland cant produce some or all of its hormones.

Hypopituitarism in children may be caused by:

Hypopituitarism can also be idiopathic, meaning that no exact cause can be determined.

The symptoms of hypopituitarism will vary depending on two things: which hormones are lacking, and your childs age. Symptoms that newborn babies may have include:

Older infants and children may have these symptoms:

Because the symptoms of hypopituitarism may resemble other conditions or medical problems, you should always consult your child's physician for a diagnosis.

Q: What is hypopituitarism?

A: Hypopituitarism occurs when the anterior (front) lobe of the pituitary gland loses its ability to make hormones, resulting in multiple pituitary hormone deficiencies. Physical symptoms depend on which hormones are no longer being produced by the gland.

Q: What causes hypopituitarism?

A: Hypopituitarism may be caused by many different conditions, including:

Hypopituitarism can also be idiopathic, meaning that no exact cause can be determined.

Q: Is hypopituitarism treatable?

A: Treating hypopituitarism depends both on its cause and on which hormones are missing. The goal of treatment is to restore normal levels of hormones. Treating the underlying condition thats causing your childs hypopituitarism often leads to a full recovery.

Since your childs body is unable to make some or all of these missing hormones, life-long hormone replacement therapy is necessary. Replacement therapy needs to be monitored and adjusted, but the extent of your childs pituitary deficiency will determine how often he will need to see his doctor.

Q: How safe is treatment?

A: While there are many potential side effects, researchers generally agree that hormone replacement therapy is safe and effective.

You and your family are key players in your childs medical care. Its important that you share your observations and ideas with your childs health care provider and that you understand your providers recommendations.

If your child is experiencing symptoms of hypopituitarism and youve set up an appointment, you probably already have some ideas and questions on your mind. But at the appointment, it can be easy to forget the questions you wanted to ask. Its often helpful to jot them down ahead of time so that you can leave the appointment feeling like you have the information you need.

If your child is old enough, you may want to suggest that she write down what she wants to ask her health care provider, too.

Some of the questions you may want to ask include:

Link:
Hypopituitarism Symptoms & Causes | Boston Children's Hospital

Endocrine Diseases in Pregnancy | GLOWM

INTRODUCTION

Pregnancy is a unique clinical scenario in which several endocrine disorders may be more frequent and/or have specific considerations for diagnosis and treatment. In this review, anterior pituitary insufficiency, adrenal, parathyroid, and thyroid disorders of pregnancy are discussed.

Anterior pituitary insufficiency is an uncommon disease. The etiology includes destruction of the anterior pituitary gland by tumors, infarction (postpartum necrosis or Sheehan's syndrome), idiopathic disease (Simmonds' disease), surgery, and radiotherapy to the pituitary gland. There have also been reports of pituitary necrosis in patients with elevated intracerebral pressure.1 Disease of the hypothalamus affecting the secretion of releasing hormones may produce a similar clinical picture; some cases of Sheehan's syndrome and idiopathic hypopituitarism are due to hypothalamic diseases.2 Finally, congenital hypopituitarism is a rare diagnosis among newborn infants.3

Sheehans syndrome

The most common cause of panhypopituitarism in women of childbearing age is postpartum necrosis, or Sheehan's syndrome.4 The pathogenesis is not clear, although Sheehan in his original description did associate it with severe postpartum hemorrhage.5 Although the classic clinical etiology of Sheehan's syndrome in about 90% of patients is severe bleeding of the anterior pituitary during delivery or immediately postpartum, no catastrophic event can be detected in more than 10% of patients.

Lack of lactation after delivery, amenorrhea, loss of pubic and axillary hair or failure of pubic hair to grow back, anorexia and nausea, lethargy and weakness, and weight loss are typical presenting signs and symptoms. On physical examination, the findings depend on the severity and duration of the disease. Commonly, the skin has a waxy character with fine wrinkles about the eyes and mouth. There is some periorbital edema, and a decrease in pigmentation is often seen. Axillary and pubic hair becomes increasingly sparse. Atrophy of the breast tissue may be present. Even in those patients losing weight, cachexia is not a feature of the disease. Hypotension may be present, and normocytic anemia is common. However, this full constellation of symptoms does not occur in every patient, and it is not unusual for the full-blown picture to take 1020 years to develop. Occasionally, the diagnosis is made when the patient develops acute adrenal insufficiency secondary to a stressful situation (e.g. infection, trauma, surgery).

It was recognized by Sheehan that not all patients with pituitary apoplexy develop panhypopituitarism, and partial pituitary insufficiency is not uncommon. In one retrospective case series of 44 patients in France, only 88% had hypopituitarism, with adrenocorticotropic hormone (ACTH) deficiency most common (70%).6 A few patients with partial hypopituitarism may present with the classic syndrome of acute panhypopituitarism with deficiency of all pituitary hormones. However, after treatment with corticosteroids alone, there is a spontaneous normalization in the menstrual cycle, with a return of thyroid test results to normal limits.

Successful pregnancies following a diagnosis of Sheehan's syndrome have been reported.7, 8, 9 In a few patients, the diagnosis of partial hypopituitarism may occur upon the presentation of a pregnancy. Although several patients conceive after treatment with gonadotropin, others conceive spontaneously, an indication of partial pituitary failure. Placental function is not altered in patients with pituitary insufficiency.

Pituitary adenoma

During normal pregnancy, the pituitary enlarges by approximately one-third of its size.10 Pituitary insufficiency in women of childbearing age may result in the setting of a pituitary tumor, usually in association with increased production of prolactin. The most common symptom is secondary amenorrhea with galactorrhea, although cases of primary amenorrhea have been reported. When there is local expansion of the tumor, patients may have neurologic symptoms, such as headache or bilateral temporal hemianopia. In such cases, other pituitary hormones may become affected with growth hormone, ACTH, and thyrotropin-stimulating hormone (TSH) deficiencies.

The diagnosis is confirmed by the use of appropriate tests to investigate each of the pituitary hormones. Baseline or random determination of serum pituitary hormone concentrations is of no value in the diagnosis of the disease; dynamic tests to evaluate pituitary reserve must be used. The most practical tests are presented in Table 1. However, their use in pregnancy is limited because of the blunted response of many of these tests.

Table 1. Tests of anterior pituitary hormone reserve

Hormone

Test

Normal Response

Response in Pregnancy

GH

L-Dopa, 500 mg, GH levels at 0, 1, 2 hour

by 10 ng/dl

Blunted

Insulin hypoglycemia 0.1 U regular IV/kg, then draw GH at 0, 20, 60, 90 min

by 10 ng/dl

Blunted

ACTH

Insulin hypoglycemia (see above), then draw cortisol at 0, 20, 60, 90 min

by 10 g/dl

Blunted

Metyrapone 750 mg every 4 hour 6

Urinary 17-KGS

Blunted

TSH

Free thyroxine index

Normal

Serum TSH

Normal

Prolactin

Can no longer be tested, given the inavailability of TRH

LH-FSH

Assess by regularity/presence of menses

When anterior pituitary insufficiency develops in pregnancy, the clinical manifestations may be local signs, such as headaches and visual disturbances, which are the consequence of an acute enlargement of, or bleeding into, the pituitary gland.11 The initial manifestations also could be related to endocrine deficiency, mainly hypoglycemia, nausea, vomiting, and hypotension secondary to ACTH deficiency.

Isolated ACTH deficiency is rare and has been infrequently described.12, 13 Acute enlargement of the pituitary gland is characterized by severe, deep, midline headaches (lasting for 23 days) and visual field disturbances. Severe hypoglycemia with convulsions and coma, unresponsive to large doses of glucose, but rapidly reversible after the administration of hydrocortisone, can be seen.

Partial or total hypopituitarism developing in patients with diabetes mellitus has been reported.14 In a review of 31 cases (19 women), the episode was associated with pregnancy in 11 (during the postpartum period in seven and during the antepartum period in four, with three maternal deaths).15 The mean age of the patients in this case series was 27 years, and the mean duration of their diabetes mellitus was 6 years, which makes vascular complication an unlikely cause of pituitary insufficiency. Furthermore, no specific vascular changes were found in the examined pituitary glands. Characteristically, the patients developed severe headaches that lasted for a few days with or without visual field disturbances, and a decrease in insulin requirement was observed. There was a high proportion of women with fetal loss. Although the mechanism supporting the increased risk of hypopituitarism among individuals with diabetes mellitus remains unclear, an association between pituitary antibodies and type 1 diabetes mellitus has been described.16

Lymphocytic hypophysitis

Lymphocytic hypophysitis can be another cause of pituitary dysfunction,17 and in pregnant women, usually presents close to delivery or in the immediate postpartum period.18 Sheehan described lymphocytic infiltration of the pituitary gland in some women with postpartum pituitary insufficiency,19 and it is possible that many of the cases mentioned above were due to lymphocytic hypophysitis.

The clinical presentation may be characterized by headaches and visual disturbances related to pressure from the expanding lesion mimicking a pituitary tumor;20, 21 spontaneous regression of the lesion was seen in several cases.22 diabetes insipidus and galactorrhea. Report of a case and review of the literature) The differential diagnosis between pituitary tumor and hypophysitis can be made only by histologic examination.18 Conversely, the patient may present with signs and symptoms of hypopituitarism, such as protracted hypoglycemia responding to glucocorticoid therapy and hypotension. It can also present in the postpartum period as pituitary insufficiency, similar to Sheehan's syndrome without the history of profound bleeding.22, 23, 24, 25

Involvement of other endocrine glands has been recognized, consistent with the concept of an autoimmune disease,26 in addition to antibodies against pituitary cells.27 It is possible that these cases are typical of the autoimmune polyendocrine deficiency syndrome that may be exacerbated during pregnancy or in the immediate postpartum period.

Treatment

Patients with partial or total hypopituitarism who become pregnant spontaneously or after treatment with gonadotropins may carry a normal pregnancy with no increase in the dose of corticosteroid replacement therapy. The usual amount of hydrocortisone in patients with pituitary insufficiency is 2030 mg/day (two-thirds of the total amount in the morning and one-third in the evening). In some instances, the amount of hydrocortisone can be decreased by one-third of the total dose because the effect of hydrocortisone is potentiated during pregnancy by estrogen.28 However, this potentiation does not occur when synthetic corticosteroids (i.e. prednisone, dexamethasone) are used. The equivalent amounts of prednisone and dexamethasone, respectively, are 5.07.5 mg daily and 0.50.75 mg daily. Because these patients have ACTH deficiency, aldosterone secretion is normal and there is no need for mineralocorticoid replacement therapy. If thyroid deficiency is present, the amount of levothyroxine needed for replacement is usually 0.10.2 g daily.

Successful pregnancy in cases of isolated growth hormone deficiency has been reported.29, 30 In these patients, lactation was unimpaired and placental function studies and intrauterine growth were normal.

The most common pituitary tumor diagnosed in women of childbearing age is a prolactinoma.31 It can be accompanied by amenorrhea, oligohypomenorrhea, and anovulation, and with or without galactorrhea. Hyperprolactinemia decreases gonadotropin-releasing hormone (GnRH) secretion, accounting for the infertility observed in these patients. Pituitary tumors are divided, according to size, into microadenomas (less than 10 mm in diameter) and macroadenomas (greater than 10 mm in diameter); the latter are further classified according to suprasellar extension and invasion of adjacent structures. Serum prolactin concentrations correlate fairly well with the size of the tumor. Hyperprolactinemia in the absence of a pituitary adenoma (idiopathic hyperprolactinemia) is a common finding.

Complications

Serum prolactin levels in women with prepregnancy hyperprolactinemia, with a few exceptions, remained unchanged during pregnancy. It was shown that prolactin levels did not change significantly in most women with baseline prolactin levels of over 60 pg/dL.32 However, in those patients with prolactin levels of less than 60 pg/dL, the mean level doubled at the end of pregnancy and returned to pretreatment levels at the end of lactation. Therefore, serum prolactin determination during pregnancy is not a predictor of tumor growth and is of no value in monitoring tumor growth.

The incidence of complications during pregnancy in patients with pituitary tumors varies according to tumor size. Due to the stimulatory effect of estrogen on lactotrophs, the size of the tumor increases in 2.7% of microprolactinomas and 22.9% of macroprolactinomas during pregnancy.31 In one study of 56 pregnant women with microprolactinomas, one developed headaches and five showed mild tumor growth.33 In studies of pregnant women with macroprolactinomas, the proportion of women developing neurologic symptoms and visual disturbances is significantly decreased upon treatment.31

Complications can occur at any stage of pregnancy. In patients with microadenomas, visual field examinations are indicated only if there are signs and symptoms of tumor enlargement, in which case an MRI is also indicated. If there is any objective evidence of tumor enlargement, bromocriptine is resumed and continued throughout pregnancy at up to 20 mg/day. If after a few days there is no improvement, dexamethasone 4 mg every 6 hours can be added. Surgery is indicated in those complicated cases not responding to the above therapies, but the recurrence rate is high among those with invasive prolactinomas even after surgery.34

Breastfeeding is not contraindicated in mothers with a diagnosis of prolactinoma. There is no difference in the remission rates of women with prolactinomas managed with dopamine-receptor agonists who breastfeed following delivery versus those who do not.35 It is advisable in patients with microadenomas to measure prolactin levels a few months after delivery and to reinstate bromocriptine therapy in the presence of persistent hyperprolactinemia. A pituitary MRI should be repeated in cases of macroprolactinoma soon after delivery because of the potential for tumor size increase.

Treatment

Once the diagnosis of prolactinoma is made, several types of therapy are available. The choice of therapy depends on tumor size, radiologic classification, local symptoms, and the patient's age and desire for pregnancy or current pregnancy.36

Medical therapy with dopamine-receptor agonists has been very effective in producing ovulation among hyperprolactinemic women37 and restores ovulation in approximately 90% of cases.31 Bromocriptine has historically been the preferred option, and no significant adverse effects have been observed in over 6000 pregnancies managed with bromocriptine.38 Most patients respond to doses of 2.55 mg/day, although occasionally a dose of 7.5 mg/day or more is needed. Bromocriptine is effective not only in normalizing prolactin levels but also in reducing the size of the tumor.31 It is advisable to use mechanical contraception during the first few months of bromocriptine therapy until the rhythm of the menstrual period is established. In those patients who have side effects such as nausea and vomiting, the oral bromocriptine tablet can be administered vaginally.39

Cabergoline is another dopamine-receptor agonist which can be considered.40 Although only 800 pregnancies have been reported with its use, there similarly does not appear to be any increased risks of preterm delivery or congenital malformations associated with this medication.38 In one 10-year observational study of 143 women, carbergoline therapy during pregnancy resulted in the ability of nearly 98% of the women to breastfeed following delivery.41 Once conception takes place, the dopamine-receptor agonist should be discontinued and the patient followed closely. For women in whom the macroprolactinoma is likely to increase, or in whom pressure symptoms occur, therapy during pregnancy should be continued.42

Radiation therapy as the initial and only therapy is seldom indicated, as medical therapy is usually very effective. The duration required for radiation therapy to normalize serum prolactin levels is lengthy and may produce hypopituitarism as a last sequela. Radiation therapy is indicated in those with prolactinomas refractory to conventional therapy.43

Surgical treatment, mainly transsphenoidal adenectomy, has been effective in restoring ovulation in patients with small tumors.32 The cure rate (i.e. sustained normalization of serum prolactin concentrations) is about approximately 70% at both 5 and 10 years of follow up; the associated proportion of successful pregnancy was similar.44 The best results are obtained in patients with microadenomas with low initial serum prolactin levels and lack of abnormal postoperative residual tissue.45

A recommended treatment approach in patients who wish to conceive is summarized in Table 2. It is suggested that treatment with bromocriptine be continued for at least 12 months before conception because it seems to reduce the risk of tumor enlargement during pregnancy.46

Table 2. Management of women with pre-conception hyperprolactinemia

Visual field monthly

*Therapy for 1 year before conception

Acromegaly is a chronic disease caused by hypersecretion of growth hormone by the adenohypophysis of the pituitary gland. It is almost always associated with a benign pituitary tumor and is characterized by slow and progressive enlargement of the acral parts. Facial changes are typical, but they usually develop so gradually that neither the family nor the patient recognizes the changes. As in other endocrine disorders, comparison of the patient's photographs taken over many years may be the only clue to the progression of the disease. Symptoms may be due to local expansion of the tumor (i.e. headaches and visual field disturbances), or they may be due to the somatic effects of chronic excess growth hormone, such as hyperhidrosis, weight gain, arthralgias, and acroparesthesia (carpal tunnel syndrome). Most women with acromegaly have been reported to suffer from oligohypomenorrhea or amenorrhea. In addition to the bony deformities, organomegaly (particularly enlargement of the heart, thyroid, and liver) is not uncommon on physical examination. The skin appears coarse and leathery. Galactorrhea with hyperprolactinemia is a common finding.

Diagnosis

The diagnosis is confirmed by an elevation in plasma insulin-like growth factor 1 (IGF-1) levels and a lack of suppression of growth hormone following the administration of a glucose load.47 However, IGF-1 levels may not be reliable during pregnancy, as they can be physiologically increased48 or decreased during pregnancy.49

Thus, suspected cases of acromegaly among pregnant women should be confirmed with a growth hormone suppression test, which requires determination of plasma growth hormone levels before and 1 and 2 hours after the administration of a solution of 100 g glucose orally. A normal response is characterized by growth hormone levels lower than 1 g/L after glucose administration. Patients with acromegaly typically have elevated baseline IGF-1 levels and respond to the glucose load with no growth hormone suppression of growth hormone concentration or even occasionally with a paradoxical increase.

In patients with acromegaly, there are increased risks of several associated cormorbidities, including hypertension, diabetes mellitus, cardiovascular disease, osteoarthritis, and sleep apnea, which should be evaluated for upon the confirmed diagnosis of acromegaly.47

Treatment

Treatment is mandatory in patients with the disease because the long-term prognosis is poor; untreated individuals have an almost 3-fold increased mortality rate.48 Conventional pituitary irradiation, transsphenoidal hypophysectomy,50 and drug therapy with octreotide (or other somatostatin receptor analogues) or the growth receptor antagonist, pegvisomant51 are used most often and can improve disease survival.52

Acromegaly during pregnancy

There are limited data of successful pregnancies in women with acromegaly. In 1954, Abelove and colleagues reported two normal pregnancies in an acromegalic woman and reviewed 33 reported cases from the world literature.53 Since that time, several other cases have been published, including a recent report of ten pregnancies among eight acromegalic women in Brazil, in which plasma IGF-1 levels were not significantly changed during gestation.54 In most instances, the infants have been reported as being normal. However, in a case described by Fisch et al.,55 the infant was born with acromegalic features. In this infant, growth was above average during the neonatal period, but a normal growth pattern subsequently returned, although no serum laboratory measurements were obtained. The lack of acromegalic features in most cases is in accordance with the report by King and colleagues demonstrating no placental transfer of growth hormone from mother to fetus.56

Historically, bromocriptine has been used as a successful treatment to induce pregnancy in patients with acromegaly.57, 58 In each of these cases, pregnancy occurred in spite of persistent elevated serum growth hormone levels.

The current guidelines for management of acromegalic women during pregnancy have been summarized in the 2014 Endocrine Society guidelines for acromegaly.47 In general, discontinuation of long-acting medical therapy (somatostatin receptor analogues or pegvisomant) is recommended approximately 2 months prior to attempting to conceive; therapy can be replaced with short-acting octreotide instead during the pre-conception period. During gestation, medical therapy should only be administered only for tumor and headache control, and plasma growth hormone and IGF-1 levels should not be monitored.

Diabetes insipidus is an uncommon disease characterized by polyuria and polydipsia due to a deficiency of antidiuretic hormone (central or neurogenic diabetes insipidus) or the peripheral resistance to the antidiuretic hormone at the renal tubules (nephrogenic diabetes insipidus). Central diabetes insipidus may be a result of a lesion at the level of the hypothalamus or pituitary gland. It may arise following hypophysectomy, invasion of the neurohypophysis by tumors, malignant metastasis (i.e. breast cancer), trauma, granulomas, or infection. In 50% of cases, however, it is considered idiopathic, with some causes probably on an autoimmune basis. Nephrogenic diabetes insipidus is a hereditary disorder affecting males; therefore, symptomatic women carriers are extremely rare. Several cases of transient nephrogenic diabetes insipidus during pregnancy and/or postpartum have been reported. A third type of diabetes insipidus, called psychogenic, which is rarely reported in pregnancy,59 is differentiated from the other two in most cases by the results of the water deprivation test.

Diagnosis

Link:
Endocrine Diseases in Pregnancy | GLOWM

Non-Functioning Tumors (Endocrine-Inactive Tumors …

As their name indicates, these relatively common pituitary adenomas do not result in excess hormone production. Instead they typically cause symptoms because of increasing size and pressure effect on the normal pituitary gland and on structures near the pituitary such as the optic nerves and chiasm. The major symptoms of patients with endocrine-inactive tumors are those of pituitary failure (hypopituitarism), visual loss and headache. Hypopituitarism may manifest itself as nausea, vomiting, weakness, decreased mental function, loss of sexual drive, infertility and in women, irregular or absent periods (amenorrhea). The vast majority of these tumors are benign. Most are macroadenomas (over 1 cm in size) when finally diagnosed. Occasionally, they grow quite large and into the cavernous sinus causing nerve compression and double vision. Some patients with large tumors may have acute hemorrhage into the tumor (pituitary apoplexy) causing relatively sudden onset of headache, visual loss, double vision, and/or pituitary failure. Endocrine-inactive adenomas may also be discovered incidentally during an evaluation for another problem, such as a head injury. Almost half of endocrine-inactive adenomas secrete part of a hormone called the alpha-subunit, which is not hormonally active but can be measured in the blood.

In patients with symptoms suggestive of pituitary failure (hypopituitarism), a complete endocrinological evaluation should be performed. These blood tests should include:

Based on the results of these tests, additional hormonal studies may be ordered.

For patients with visual complaints, an ophthalmologist (preferably a neuro-ophthalmologist should evaluate the patient. This evaluation should include acuity testing of each eye and formal visual field testing to determine if there is loss of peripheral vision.

An MRI of the pituitary without and with gadolinium (contrast agent) is the preferred study for visualizing a pituitary tumor. In most instances, a CT scan without and with contrast will also detect an adenoma. In a minority of cases instances it may be difficult to distinguish an adenoma of the pituitary from other masses. These masses include:

For the great majority of patients with symptomatic endocrine-inactive adenomas, transsphenoidal surgery and adenoma removal is the preferred and most effective therapy. The long-term cure or control rate is approximately 70-80% overall. The cure rate is generally higher for smaller tumors and those that do not invade the cavernous sinus; conversely, the cure rate is lower for larger tumors (over 3 cm) and those that do invade the cavernous sinus. Overall, transsphenoidal tumor resection results in an improvement in visual acuity and visual field deficits in 75-90% of patients, headache resolution in 80-90% of patients, and improvement in hypopituitarism in only 10-30% of patients. Patients who do not have hormonal recovery after surgery will require long-term hormone replacement therapy. Because the transsphenoidal approach is so effective and relatively safe, it is rare that even large macroadenomas warrant a transcranial operation as the initial procedure.

There is no known effective medical therapy that reliably slows or stops growth of endocrine inactive adenomas.

Radiation is generally used as a second line therapy for endocrine-inactive tumors. For patients who have residual tumor after the initial surgery, radiation or repeat transsphenoidal surgery or both are generally indicated if the tumor grows as seen on subsequent MRIs. Both conventional (external beam) and stereotactic radiosurgery are relatively effective in controlling growth, but stereotactic radiation can deliver a higher radiation dose to the tumor more safely. Consequently it is the preferred radiation technique. Also, external beam radiation reliably causes loss of remaining normal pituitary function over 5 to 10 years. Stereotactic radiosurgery may also cause loss of pituitary function, but less frequently then external beam radiation.

Read more:
Non-Functioning Tumors (Endocrine-Inactive Tumors ...

Steroid Replacement Doses for Hypopituitary Patients …

Question: I am completely hypopituitary and had a bilateral adrenalectomy to control my Cushings. I now have Nelsons Syndrome and am on 30mg/day of hydrocortisone replacement. I still have uncontrollable diabetes, muscle weakness and look and feel like I still have Cushings. Is this normal for Nelsons or could my replacement dose be too high?

Answer: Patients who have had a bilateral adrenalectomy for treatment of Cushings disease and are on adequate hydrocortisone replacement should not have any persistent symptoms of Cushings syndrome. Nelson syndrome which occurs when there is an ACTH-secreting pituitary tumor is associated with increased pigmentation of the skin and if the tumor has enlarged, symptoms of tumor growth affecting vision. The problem that may arise on hydrocortisone is that the dose may be excessive for the patients optimal replacement and this hydrocortisone then causes symptoms of Cushings. Patients with hypopituitarism frequently have decreased clearance of cortisol and require a lower dose for maintenance. A good way of determining the right replacement dose of hydrocortisone is to measure urine free cortisol while taking the dose of hydrocortisone in question. Values should be in the middle of the normal reference range. Occasionally patients with hypopituitarism who need hydrocortisone replacement require only small doses of hydrocortisone, from 10 to 15 mg daily.

By Dr. David E. Schteingart MD (Summer, 2005)

Continue reading here:
Steroid Replacement Doses for Hypopituitary Patients ...

Hypopituitarism | UCLA Health

Definition: Hypopituitarism is a condition caused by low levels of pituitary hormones.

Alternative Names: Pituitary insufficiency

Causes, incidence, and risk factors: The pituitary gland is a small structure that is located just below the brain. It is attached by a stalk to the hypothalamus, the area of the brain that controls its function.

The hormones secreted by the pituitary gland (and their functions) are:

In hypopituitarism, there is an absence of one or more pituitary hormones. Lack of the hormone leads to loss of function in the gland or organ that it controls. For example, loss of thyroid stimulating hormone leads to loss of function in the thyroid gland.

Hypopituitarism may be caused by tumors of the pituitary gland or hypothalamus, head trauma, brain tumor, radiation, brain surgery, stroke, subarachnoid hemorrhage (from a burst aneurysm), or infections of the brain and the tissues that support the brain. Occasionally, hypopituitarism is due to uncommon immune system or metabolic diseases, such as sarcoidosis, histiocytosis X, and hemochromatosis.

Hypopituitarism is also a rare complication following pregnancy, a condition called Sheehan's syndrome. The cause of this type of hypopituitarism is unknown.

Symptoms:

Note: Symptoms may develop slowly and may vary greatly, depending upon the severity of the disorder, the number of deficient hormones, and their target organs.

Additional symptoms that may be associated with this disease:

Signs and tests:

Diagnosis of hypopituitarism must confirm low hormone levels due to an abnormality of the pituitary gland. The diagnosis must also rule out disease of the organ affected by this hormone.

In some cases, one of the hormones produced by the pituitary may be elevated in the blood stream if a patient has a pituitary tumor which is producing an excessive amount of that hormone. The tumor itself may be crushing the rest of the cells of the pituitary, leading to low levels of other hormones.

Treatment: If hypopituitarism is caused by a tumor, treatment by surgical removal, with or without radiation therapy, may be indicated. Replacement of deficient hormones is often required even after successful treatment of a pituitary tumor.

Hormone therapy is needed to replace hormones that are no longer made by the organs under the control of the pituitary gland. These may include corticosteroids (cortisol), thyroid hormone, sex hormones (testosterone for men and estrogen for women), and growth hormone. Drugs are also available to treat associated infertility in men and women.

Support Groups:

Expectations (prognosis): Hypopituitarism is usually permanent and requires life-long treatment; however, a normal life span can be expected.

Complications: Side effects of drug therapy can develop.

Calling your health care provider: Call your health care provider if symptoms of hypopituitarism develop.

Prevention: In most cases, the disorder is not preventable. Awareness of risk may allow early diagnosis and treatment.

Read more:
Hypopituitarism | UCLA Health

Hypopituitarism Disease Reference Guide – Drugs.com

Medically reviewed on August 22, 2017

Hypopituitarism is a rare disorder in which your pituitary gland either fails to produce one or more of its hormones or doesn't produce enough of them.

The pituitary gland is a small bean-shaped gland situated at the base of your brain, behind your nose and between your ears. Despite its size, this gland secretes hormones that influence nearly every part of your body.

In hypopituitarism, you have a short supply of one or more of these pituitary hormones. This deficiency can affect any number of your body's routine functions, such as growth, blood pressure and reproduction.

You'll likely need medications for the rest of your life to treat hypopituitarism, but your symptoms can be controlled.

Hypopituitarism is often progressive. Although the signs and symptoms can occur suddenly, they more often develop gradually. They are sometimes subtle and may be overlooked for months or even years.

Signs and symptoms of hypopituitarism vary, depending on which pituitary hormones are deficient and how severe the deficiency is. They may include:

See your doctor if you develop signs and symptoms associated with hypopituitarism.

Contact your doctor immediately if certain signs or symptoms of hypopituitarism develop suddenly or are associated with a severe headache, visual disturbances, confusion or a drop in blood pressure. Such signs and symptoms could represent sudden bleeding into the pituitary gland (pituitary apoplexy), which requires prompt medical attention.

Hypopituitarism may be the result of inherited disorders, but more often it's acquired. Hypopituitarism frequently is triggered by a tumor of the pituitary gland. As a pituitary tumor increases in size, it can compress and damage pituitary tissue, interfering with hormone production. A tumor can also compress the optic nerves, causing visual disturbances.

The cause of hypopituitarism can also be other diseases and events that damage the pituitary, such as:

Diseases of the hypothalamus, a portion of the brain situated just above the pituitary, also can cause hypopituitarism. The hypothalamus produces hormones of its own that directly affect the activity of the pituitary.

In some cases, the cause of hypopituitarism is unknown.

The pituitary gland and the hypothalamus are situated within the brain and control hormone production.

The endocrine system includes the pituitary gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, ovaries (in females) and testicles (in males).

If your doctor suspects a pituitary disorder, he or she will likely order several tests to check levels of various hormones in your body. Your doctor may also want to check for hypopituitarism if you've had a recent head injury or radiation treatment that might have put you at risk of damage to your pituitary gland.

Tests your doctor may order include:

Successful treatment of the underlying condition causing hypopituitarism may lead to a complete or partial recovery of your body's normal production of pituitary hormones. Treatment with the appropriate hormones is often the first step. These drugs are considered as "replacement," rather than treatment, because the dosages are set to match the amounts that your body would normally manufacture if it didn't have a pituitary problem. Treatment may be lifelong.

Treatment for pituitary tumors may involve surgery to remove the growth. In some instances, doctors also recommend radiation treatment.

Hormone replacement medications may include:

If you've become infertile, LH and FSH (gonadotropins) can be administered by injection to stimulate ovulation in women and sperm production in men.

A doctor who specializes in endocrine disorders (endocrinologist) may monitor the levels of these hormones in your blood to ensure you're getting adequate but not excessive amounts.

Your doctor will advise you to adjust your dosage of corticosteroids if you become seriously ill or experience major physical stress. During these times, your body would ordinarily produce extra cortisol hormone. The same kind of fine-tuning of dosage may be necessary when you have the flu, experience diarrhea or vomiting, or have surgery or dental procedures. Adjustments in dosage may also be necessary during pregnancy or with marked changes in weight. You may need periodic CT or MRI scans as well to monitor a pituitary tumor or other diseases causing the hypopituitarism.

Wear a medical alert bracelet or pendant, and carry a special card, notifying others in emergency situations, for example that you're taking corticosteroids and other medications.

You're likely to start by seeing your family doctor or a general practitioner. However, in some cases, when you call to set up an appointment, you may be referred to a specialist called an endocrinologist.

Here's some information to help you prepare for your appointment.

Create a list of questions before your appointment so that you can make the most of your time with your doctor. For hypopituitarism, some basic questions to ask your doctor include:

Don't hesitate to ask any questions you have during your appointment.

Your doctor is likely to ask you some questions, such as:

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Hypopituitarism Disease Reference Guide - Drugs.com

Hypopituitarism Treatment & Causes | Lurie Children’s

Hypopituitarism (an underactive pituitary gland) is rare in children. When a child has hypopituitarism, the pituitary gland has lost its ability to make one, some or all pituitary hormones. The condition is often permanent, but very treatable.

The pituitary gland in the middle of the head and brain is the bodys master gland. The table below describes what each hormone made by the pituitary gland does, what happens when each hormone is missing and medication that can replace each hormone.

In children, hypopituitarism is usually caused by something congenital (the child is born with the problem) or by a pituitary tumor. The tumor interferes with the gland. Sometimes, the cause cannot be determined.

Sometimes, the cause was present before the child was born. Often, we see that the pituitary gland is under-developed. A genetic error may be the reason the gland doesnt work well.

Children withsepto-optic dysplasia have varying degrees of hypopituitarism. Their vision is usually impaired because the optic nerves are under-developed. The eyes can move irregularly or wander. This disorder can affect the pituitary gland and other structures in the brain. Often, these children have diabetes insipidus and not enough growth hormone.

There are other forms of congenital hypopituitarism. Sometimes, the pituitary gland doesnt make enough growth hormone. Sometimes, the thyroid gland is underactive, or the adrenal gland doesnt work well. In Kallman syndrome, not enough of the hormones that stimulate the testes or ovaries are made, puberty is late or doesnt happen, and the sense of smell is affected.

A tumor can cause hypopituitarism. The tumor may grow in the pituitary gland or outside the gland, compressing the normal tissue. Parents worry that the tumor may be cancer, but thats unlikely.

Rarely, one of these conditions leads to this hormone problem:

Some hormone deficiencies cause complications over time. Our experienced doctors help you understand any long-term or serious effects of the missing hormones. For example:

Signs and symptoms vary, depending on which hormones are lacking and the childs age.

Common symptoms in newborns:

Commonsymptomsin older infants and children:

The symptoms you see may be due to other conditions and medical problems. Always talk to your childs doctor if you have a concern.

Our approach to diagnosing hypopituitarism is very thorough. We take one step at a time andminimizeinvasive procedures.

We can use other tests as needed. For example:

We know that the weeks of waiting for the full picture can be difficult. Our compassionate team and family-friendly environment support your family while we progress toward the answers and plan the right treatment. As soon as possible, youll receive a call from a doctor or nurse about what weve found and the next steps to take.

We treat the cause of the condition and replace the hormones the body isnt making.

Hormone replacement therapy mimics the bodys natural production. The medicines can be continued as long as needed, during childhood and adulthood. These medications are tolerated very well when the right amounts of hormones are replaced. The following are examples of hormone replacement therapy:

Some tumors respond to medicine that is swallowed. Other tumors need to be removed with surgery. Usually, the hormone deficiencies remain after a tumor is removed. Hormone therapy works for this.

To be effective, hormone replacement must be supported with ongoing care. Throughout childhood, we need to adjust the hormone doses to accommodate the growing childs needs and changes in symptoms. We evaluate the childs growth and development frequently and develop a working relationship with parent and child.

Our resources help bring the right specialists into your childs care to make sure the child gets the best treatment possible. Our endocrinologists and neurosurgeons co-manage patients in our hospital. Tools such as our electronic health record help nurses and doctors throughout the team work closely together.

We care for children with all forms of hypopituitarism. We treat each hormone deficiency to maintain the childs health and normal development. With the right care plan, children with hypopituitarism usually enjoy a normal life. We help the child to develop normally, interact with peers and feel well.

Learn more about pituitary disorders by visiting these physician-recommended websites:

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Hypopituitarism Treatment & Causes | Lurie Children's

Hypopituitarism | You and Your Hormones from the Society for …

Alternative names for hypopituitarism

Hypopit; pituitary insufficiency; partial hypopituitarism; panhypopituitarism (pan referring to all pituitary hormones being affected); anterior hypopituitarism

Hypopituitarism is failure of the pituitary gland to produce one, some, or all of the hormones it normally produces. The pituitary gland has two parts, the anterior pituitary and the posterior pituitary, and hormone production can be affected in both parts.

Below are listed some of the causes of hypopituitarism:

The signs and symptoms of hypopituitarism depend on which of the pituitary gland hormones are involved, to what extent and for how long. It also depends on whether the hormone deficiencies began as a child or later in adult life. Symptoms can be slow at the start and vague.It is worth understanding the normal function and effects of these hormones in order to understand the signs and symptoms of hypopituitarism. (See the article on pituitary gland.) There may also be additional symptoms due to the underlying cause of the hypopituitarism, such as the effects of pressure from a tumour.

Symptoms can include:

Hypopituitarism is rare. At any given time, between 300 and 455 people in a million may have hypopituitarism. A number of endocrinologists believe that hypopituitarism is quite common after brain injuries. If this belief is confirmed, then hypopituitarism may be significantly more common than previously believed.

Most cases of hypopituitarism are not inherited.However, there are some very rare genetic abnormalities than can cause hypopituitarism.

Blood tests are required to check the level of the hormones, which are either produced by the pituitary gland itself, or by peripheral endocrine glands controlled by the pituitary gland. These blood tests may be one-off samples or the patient may require more detailed testing on a day-unit. These are called dynamic tests and they measure hormone levels before and after stimulation to see if the normal pituitary gland is working properly.They usually last between1 to 4 hours.

If it is suspected that there is a lack of anti-diuretic hormone, the doctor may organise a water deprivation test. The patient will be deprived of water for a period of eight hours under very close supervision with regular blood and urine tests.The test may be extended to a 24 hour period if needed, which means an overnight stay in hospital.

Other tests may also be organised to try and identify the underlying cause of the hypopituitarism. These could include blood tests, scans such as computerised tomography (CT) or magnetic resonance imaging (MRI) scans, and tests for vision.

Hypopituitarism is treated by replacing the deficient hormones. Treatment will be tailored to the individual depending on which hormones they are deficient in:

Since the treatment of hypopituitarism only involves replacing hormones that the body should be making but is unable to, there should be no side-effects if the appropriate amounts of hormones are replaced.Patients will be monitored to ensure they are receiving the correct amount of replacement hormones. Some side-effects can occur from hormone replacement if the amount replaced is higher than the individuals body requirements.If the patient has any concerns, they should discuss them with their doctor.

People with long-term hypopituitarism will need to take daily medication and will require regular checks with an endocrinologist at an outpatients clinic.

People with hypopituitarism may have an impaired quality of life.Hypopituitarism is associated with an increased risk of heart disease and strokes as a result of the physical changes that occur in body fat, cholesterol and circulation. Healthy living, a balanced diet and exercise to prevent becoming overweight are essential to reduce this risk.

People with hypopituitarism also have a higher risk of developing osteoporosis or brittle bones and, therefore, have a higher risk of developing fractures from minor injuries. A diet that is rich in calcium and vitamin D along with moderate amounts of weight-bearing exercise and training are helpful in decreasing this risk.

Appropriate pituitary hormone replacement therapy can reduce all these risks.

Last reviewed: Jan 2015

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Hypopituitarism | You and Your Hormones from the Society for ...

Panhypopituitarism: Practice Essentials, Pathophysiology …

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Panhypopituitarism: Practice Essentials, Pathophysiology ...

Hypopituitarism | Lifespan

What is hypopituitarism?

Hypopituitarism happens when your pituitary gland is not active enough. As a result the gland does not make enough pituitary hormones.

The pituitary is a small gland at the base of your brain. It is one of several glands that make hormones. Hormones are chemicals that send information and instructions from one set of cells to another. The pituitary gland makes many types of hormones. These hormones affect many things, including bone and tissue growth, your thyroid gland, and sexual development and reproduction.

Causes can directly affect the pituitary gland. Or they can indirectly affect the glandthrough changes inthe hypothalamus. This is a part of the brain that is just above the pituitary gland.

Direct causes include:

Indirect causes include:

Symptoms are different for each person. They may happen over time or right away. They depend on which hormones the pituitary gland is not making enough of. These hormone deficiencies, and the symptoms they cause, include:

These symptoms may look like other health problems. Always see your healthcare provider for a diagnosis.

Your healthcare provider will ask about your medical history. You will also need an exam. Other tests you may need include:

Your healthcare provider will figure out the best treatment for you based on:

Treatment depends on what is causing the condition. The treatment goal is to have the pituitary gland work as it should. Treatment may include:

Tell your healthcare provider if your symptoms get worse or you have new symptoms.

Tips to help you get the most from a visit to your healthcare provider:

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Hypopituitarism | Lifespan

OMIM Entry – # 146510 – PALLISTER-HALL SYNDROME; PHS

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Biesecker, L. G., Kang, S., Schaffer, A. A., Abbott, M., Kelley, R. I., Allen, J. C., Clericuzio, C., Grebe, T., Olney, A., Graham, J. M., Jr. Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome. J. Med. Genet. 33: 947-951, 1996. [PubMed: 8950676] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=8950676%5D

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Demurger, F., Ichkou, A., Mougou-Zerelli, S., Le Merrer, M., Goudefroye, G., Delezoide, A.-L., Quelin, C., Manouvrier, S., Baujat, G., Fradin, M., Pasquier, L., Megarbane, A., and 40 others. New insights into genotype-phenotype correlation for GLI3 mutations. Europ. J. Hum. Genet. 23: 92-102, 2015. [PubMed: 24736735] [Full Text: https://dx.doi.org/10.1038/ejhg.2014.62%5D

Donnai, D., Burn, J., Hughes, H. Smith-Lemli-Opitz syndromes: do they include the Pallister-Hall syndrome? (Letter) Am. J. Med. Genet. 28: 741-743, 1987. [PubMed: 3425639] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1987&volume=28&issue=3&spage=741%5D

Finnigan, D. P., Clarren, S. K., Haas, J. E. Extending the Pallister-Hall syndrome to include other central nervous system malformations. Am. J. Med. Genet. 40: 395-400, 1991. [PubMed: 1746599] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1991&volume=40&issue=4&spage=395%5D

Galasso, C., Scire, G., Fabbri, F., Spadoni, G. L., Killoran, C. E., Biesecker, L. G., Boscherini, B. Long-term treatment with growth hormone improves final height in a patient with Pallister-Hall syndrome. Am. J. Med. Genet. 99: 128-131, 2001. [PubMed: 11241471] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=2001&volume=99&issue=2&spage=128%5D

Graham, J. M., Perl, D., O'Keefe, T., Rawnsley, E., Little, G. A. Apparent familial recurrence of hypothalamic hamartoblastoma syndrome. (Abstract) Proc. Greenwood Genet. Center 2: 117-118, 1983.

Hall, J. G., Pallister, P. D., Clarren, S. K., Beckwith, J. B., Wiglesworth, F. W., Fraser, F. C., Cho, S., Benke, P. J., Reed, S. D. Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly--a new syndrome? Part I: clinical, causal, and pathogenetic considerations. Am. J. Med. Genet. 7: 47-74, 1980. [PubMed: 7211952] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1980&volume=7&issue=1&spage=47%5D

Huff, D. S., Fernandes, M. Two cases of congenital hypothalamic hamartoblastoma, polydactyly, and other congenital anomalies (Pallister-Hall syndrome). (Letter) New Eng. J. Med. 306: 430-431, 1982. [PubMed: 7057839] [Full Text: http://www.nejm.org/doi/abs/10.1056/NEJM198202183060719?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed%5D

Iafolla, K., Fratkin, J. D., Spiegel, P. K., Cohen, M. M., Jr., Graham, J. M., Jr. Case report and delineation of the congenital hypothalamic hamartoblastoma syndrome (Pallister-Hall syndrome). Am. J. Med. Genet. 33: 489-499, 1989. [PubMed: 2688416] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1989&volume=33&issue=4&spage=489%5D

Johnston, J. J., Olivos-Glander, I., Killoran, C., Elson, E., Turner, J. T., Peters, K. F., Abbott, M. H., Aughton, D. J., Aylsworth, A. S., Bamshad, M. J., Booth, C., Curry, C. J., and 36 others. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am. J. Hum. Genet. 76: 609-622, 2005. [PubMed: 15739154] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)62872-9%5D

Kang, S., Allen, J., Graham, J. M., Jr., Grebe, T., Clericuzio, C., Patronas, N., Ondrey, F., Green, E., Schaffer, A., Abbott, M., Biesecker, L. G. Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. J. Med. Genet. 34: 441-446, 1997. [PubMed: 9192261] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=9192261%5D

Kang, S., Graham, J. M., Jr., Abbott, M., Schaffer, A., Green, E. D., Rosenberg, M., Allen, J., Clericuzio, C., Grebe, T., Haskins-Olney, A., Biesecker, L. G. Autosomal dominant Pallister-Hall syndrome maps to 7p13. (Abstract) Am. J. Hum. Genet. 59 (suppl.): A17 only, 1996.

Kang, S., Graham, J. M., Jr., Olney, A. H., Biesecker, L. G. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nature Genet. 15: 266-268, 1997. [PubMed: 9054938] [Full Text: https://dx.doi.org/10.1038/ng0397-266%5D

Killoran, C. E., Abbott, M., McKusick, V. A., Biesecker, L. G. Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis. Clin. Genet. 58: 28-30, 2000. [PubMed: 10945658] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9163&date=2000&volume=58&issue=1&spage=28%5D

Kletter, G. B., Biesecker, L. G. Male-to-male transmission of the Pallister-Hall syndrome. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A100 only, 1992.

Kuller, J. A., Cox, V. A., Schonberg, S. A., Golabi, M. Pallister-Hall syndrome associated with an unbalanced chromosome translocation. Am. J. Med. Genet. 43: 647-650, 1992. [PubMed: 1605268] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1992&volume=43&issue=3&spage=647%5D

Low, M., Moringlane, J. R., Reif, J., Barbier, D., Beige, G., Kolles, H., Kujat, C., Zang, K. D., Henn, W. Polysyndactyly and asymptomatic hypothalamic hamartoma in mother and son: a variant of Pallister-Hall syndrome. Clin. Genet. 48: 209-212, 1995. [PubMed: 8591673] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9163&date=1995&volume=48&issue=4&spage=209%5D

Lurie, I. W. Pallister-Hall and McKusick-Kaufmann syndromes. (Letter) J. Med. Genet. 32: 668-672, 1995. [PubMed: 7473667] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=7473667%5D

Lurie, I. W., Wulfsberg, E. A. The McKusick-Kaufmann syndrome: phenotypic variation observed in familial cases as a clue for the evaluation of sporadic cases. Genet. Counsel. 5: 275-281, 1994. [PubMed: 7811428]

Narumi, Y., Kosho, T., Tsuruta, G., Shiohara, M., Shimazaki, E., Mori, T., Shimizu, A., Igawa, Y., Nishizawa, S., Takagi, K., Kawamura, R., Wakui, F., Fukushima, Y. Genital abnormalities in Pallister-Hall syndrome: report of two patients and review of the literature. Am. J. Med. Genet. 152A: 3143-3147, 2010. [PubMed: 21108399] [Full Text: https://dx.doi.org/10.1002/ajmg.a.33720%5D

Ondrey, F., Griffith, A., Van Waes, C., Rudy, S., Peters, K., McCullagh, L., Biesecker, L. G. Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome. Am. J. Med. Genet. 94: 64-67, 2000. [PubMed: 10982485] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=2000&volume=94&issue=1&spage=64%5D

Pallister, P. D., Hecht, F., Herrman, J. Three additional cases of the congenital hypothalamic 'hamartoblastoma' (Pallister-Hall) syndrome. (Letter) Am. J. Med. Genet. 33: 500-501, 1989. [PubMed: 2596511] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1989&volume=33&issue=4&spage=500%5D

Penman Splitt, M., Wright, C., Perry, R., Burn, J. Autosomal dominant transmission of Pallister-Hall syndrome. Clin. Dysmorph. 3: 301-308, 1994. [PubMed: 7894735]

Sama, A., Mason, J. D. T., Gibbin, K. P., Young, I. D., Hewitt, M. The Pallister-Hall syndrome. (Letter) J. Med. Genet. 31: 740 only, 1994. [PubMed: 7815447] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=7815447%5D

Say, B., Gerald, P. S. A new polydactyly--imperforate-anus--vertebral-anomalies syndrome? (Letter) Lancet 292: 688 only, 1968. Note: Originally Volume II. [PubMed: 4175523] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(68)92549-X%5D

Sills, I. N., Rapaport, R., Desposito, F., Lieber, C. Familial Pallister-Hall syndrome: three affected offspring. (Letter) Am. J. Med. Genet. 52: 251 only, 1994. [PubMed: 7802025] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1994&volume=52&issue=2&spage=251%5D

Sills, I. N., Rapaport, R., Robinson, L. P., Lieber, C., Shih, L. Y., Horlick, M. N. B., Schwartz, M., Desposito, F. Familial Pallister-Hall syndrome: case report and hormonal evaluation. Am. J. Med. Genet. 47: 321-325, 1993. [PubMed: 8135274] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1993&volume=47&issue=3&spage=321%5D

Stoll, C., de Saint Martin, A., Donato, L., Alembik, Y., Sauvage, P., Messer, J. Pallister-Hall syndrome with stenosis of the cricoid cartilage and microphallus without hypopituitarism. Genet. Counsel. 12: 231-235, 2001. Note: Erratum: Genet. Counsel. 13: 69 only, 2002. [PubMed: 11693785]

Thomas, H. M., Todd, P. J., Heaf, D., Fryer, A. E. Recurrence of Pallister-Hall syndrome in two sibs. J. Med. Genet. 31: 145-147, 1994. [PubMed: 8182722] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=8182722%5D

Topf, K. F., Kletter, G. B., Kelch, R. P., Brunberg, J. A., Biesecker, L. G. Autosomal dominant transmission of the Pallister-Hall syndrome. J. Pediat. 123: 943-946, 1993. [PubMed: 8229528]

Unsinn, K. M., Neu, N., Krejci, A., Posch, A., Menardi, G., Gassner, I. Pallister-Hall syndrome and McKusick-Kaufmann (sic) syndrome: one entity? J. Med. Genet. 32: 125-128, 1995. [PubMed: 7760322] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=7760322%5D

Verloes, A. Numerical syndromology: a mathematical approach to the nosology of complex phenotypes. Am. J. Med. Genet. 55: 433-443, 1995. [PubMed: 7762583] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1995&volume=55&issue=4&spage=433%5D

Verloes, A., David, A., Ngo, L., Bottani, A. Stringent delineation of Pallister-Hall syndrome in two long surviving patients: importance of radiological anomalies of the hands. J. Med. Genet. 32: 605-611, 1995. [PubMed: 7473651] [Full Text: http://jmg.bmj.com/cgi/pmidlookup?view=long&pmid=7473651%5D

Verloes, A., Gillerot, Y., Langhendries, J.-P., Fryns, J.-P., Koulischer, L. Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome. Am. J. Med. Genet. 43: 669-677, 1992. [PubMed: 1621756] [Full Text: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1992&volume=43&issue=4&spage=669%5D

Verloes, A., Narcy, F., Fallet-Bianco, C. Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence, microphthalmia, pulmonary malformations, radial hypoplasia and mullerian regression: further delineation of a new syndrome? Clin. Dysmorph. 4: 33-37, 1995. [PubMed: 7735503]

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OMIM Entry - # 146510 - PALLISTER-HALL SYNDROME; PHS

Hypopituitarism in Children | Children’s Hospital of Philadelphia

Hypopituitarism is a condition in which the pituitary gland in the brain is not working properly. Normally, the pituitary gland produces hormones some of which affect growth, blood pressure, blood sugar and other body processes. Effects of hypopituitarism may be gradual, or sudden and dramatic.

Hypopituitarism, in children, is often caused by a benign (noncancerous) pituitary tumor, an injury, an autoimmune process, or an infection. Often, no exact cause can be determined.

Symptoms vary depending on what hormones are insufficiently producedfrom the pituitary gland. The symptoms of hypopituitarism may resemble other conditions or medical problems. Always consult yourdoctor for a diagnosis. Common symptoms include:

Small penis in males

Very low blood sugar (hypoglycemia)

Slowed growth and short stature

Slowed sexual development

Prolonged jaundice at birth

Poor appetite

Weight loss or weight gain

Sensitivity to cold

Facial puffiness

The symptoms of several underactive glands may help your child'sdoctor diagnose hypopituitarism. In addition to a complete medical history and physical exam, diagnostic procedures for hypopituitarism may include:

Computed tomography scan (also called a CT or CAT scan).A diagnostic imaging procedure that uses a combination of X-rays and computer technology to producehorizontal, or axial,images (often called slices)of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.

Magnetic resonance imaging (MRI).A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.

Blood tests. Blood tests are used to measure hormone levels.

Bone X-rays of the hand. X-rays of the left hand and wrist willdetermine bone age, which is often delayed compared with chronologic age inchildren with hypopituitarism..

Specific treatment for hypopituitarism will be determined by your child'sdoctor based on:

Your child's age, overall health, and medical history

Extent of the disease

Your child's tolerance for specific medications, procedures, or therapies

Expectations for the course of the disease

Your opinion or preference

Treatment of hypopituitarism depends on its cause. The goal of treatment is to restore the pituitary gland to normal function, producing normal levels of hormones. Treatment may include specific hormone replacement therapy, surgical tumor removal, and/or radiation therapy.

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Hypopituitarism in Children | Children's Hospital of Philadelphia

What is hypopituitarism? | The Pituitary Foundation

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The pituitary gland produces a number of hormones or chemicals which are released into the blood to control other glands in the body. If the pituitary is not producing one or more of these hormones, or not producing enough, then this condition is known as hypopituitarism.

The term Multiple Pituitary Hormone Deficiency (MPHD) is sometimes used to describe the condition when the pituitary is not producing two or more of these hormones. If all the hormones produced by the pituitary are affected this condition is known as panhypopituitarism.

Hypopituitarism is most often caused by a benign (i.e. not cancerous) tumour of the pituitary gland, or of the brain in the region of the hypothalamus. Pituitary underactivity may be caused by the direct pressure of the tumour mass on the normal pituitary or by the effects of surgery or radiotherapy used to treat the tumour. Less frequently, hypopituitarism can be caused by infections (such as meningitis) in or around the brain or by severe blood loss, by head injury, or by various rare diseases such as sarcoidosis (an illness which resembles tuberculosis).

More information about conditions which result in hypopituitarism can be found in the Rarer Disorders section.

Each of the symptoms described above occur in response to the loss of one or more of the hormones produced by the pituitary. Decrease in the production of only one hormone would not lead to all the symptoms described above.

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What is hypopituitarism? | The Pituitary Foundation

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