Pituitary incidentaloma is defined as a previously unsuspected pituitary lesion that is discovered on imaging study performed for an unrelated reason in a patient with no obvious symptoms to suggest pituitary disease.1,2 The incidence of these lesions is between 10% and 20% of the population and the prevalence can approach 1 in 1000 people.3,4

Pituitary adenoma is the most common incidentally found pituitary lesion, but the differential diagnosis of a pituitary lesion identified on imaging also includes Rathke cleft cyst, craniopharyngioma, meningioma, hypophysitis, or metastasis.2,5

Pituitary adenomas can be either functioning or nonfunctioning, the latter being the most common.2 Although functional tumors can be associated with significant symptoms secondary to the hormone excess, cases of nonfunctional pituitary tumors may present with symptoms related to the mass effect on surrounding structures, such as headache, visual defects, and hypopituitarism.6

The natural history of pituitary incidentalomas is not fully understood, but data suggest that most microincidentalomas (lesions <10 mm) have a benign course, whereas macroincidentalomas (10 mm) require more attention as the risk for hormone abnormalities and mass effects is higher.5

In the largest series of pituitary incidentalomas published in 2016,7 including 328 patients diagnosed with these tumors, researchers reported that most incidentalomas were pituitary adenomas (73%) and that approximately one-quarter (27%) of cases were nonpituitary sellar masses. There was no sex difference in the prevalence of these tumors. Most tumors were macroadenomas at presentation, likely because they were detected on imaging of the brain and not that of the sella, which may have missed smaller lesions.7

The most common indication for imaging in the case series was headache, which relates one of the controversial topics regarding the association between headaches and pituitary incidentalomas: considering the fact that headache may be one of the symptoms of pituitary tumors and that in some patients the headache resolves following removal of the tumor, would it be correct to classify these tumors as incidental?

Interestingly, pituitary incidentalomas in children have different patterns than those detected in the adulthood with a high prevalence of physiologic pituitary hypertrophy.8 As most incidentalomas in pediatric patients are not associated with hormonal hypersecretion or hypopiuitarism and structural progression is not common, it is believed that the extensive follow-up assessment recommended for adults might not be necessary for children.8

The Endocrine Society clinical practice guidelines for management of pituitary incidentaloma recommend completing a thorough history and physical examination, as well as laboratory evaluation for pituitary hormone excess or deficiency.1 Magnetic resonance imaging (MRI) should be completed in all cases that were initially diagnosed by computed tomography and visual field assessment is recommended in the presence of a tumor abutting the optic nerves or chiasm on MRI.1

There are different opinions on how to screen for pituitary hormone deficiencies, but as a general rule, the investigation should include measurements of total or free thyroxine, thyrotropin, cortisol, insulinlike growth factor-1 (IGF-1), luteinizing hormone and follicular-stimulating hormone (FSH) in men and postmenopausal women, and total testosterone in men.5 Stimulation tests should be performed for adrenocorticotropic hormone (ACTH) and growth hormone (GH) deficiency when baseline test results are not confirmatory.1,5 The most common deficits are GH deficiency and hypogonadism, followed by central hypothyroidism and secondary adrenal insufficiency.6

Significant hypopituitarism is not commonly seen with microincidentaloms.2 The Endocrine Society clinical practice guidelines strongly favor routine testing for hypopituitarism in macroincidentalomas and larger microincidentalomas measuring 6 to 9 mm, as asymptomatic pituitary hormone deficits are more likely to occur with larger lesions.1

As for hormone hypersecretion, it is recommended to include an assessment for prolactin, GH, and possibly ACTH hypersecretion.1 Although approximately half of pituitary incidentalomas are nonfunctional, prolactin-secreting pituitary tumors are the most common functional type.7 Elevated prolactin can indicate either direct tumor secretion or disconnection of the hypothalamus and normal pituitary gland by a large nonfunctioning pituitary mass.2 Silent somatotroph-secreting tumors are rare, but evaluation for GH excess is recommended by measurement of IGF-1 level, as treatment could reduce long-term morbidity. When clinically suspected, laboratory screening for glucocorticoid excess and Cushing syndrome is suggested.1

The available natural history data on pituitary incidentalomas are mostly derived from small-scale studies with relatively limited follow-up and the risk of developing hormonal dysfunction over longer follow-up is unknown.7 A systematic review and meta-analysis to assess the natural history of nonfunctioning pituitary adenomas revealed that tumor growth was more common in macroadenomas (12.5 per 100 person-years) and solid lesions (5.7 per 100 person-years) compared with the incidence of tumor growth in microadenomas (3.3 per 100 person-years) and cystic lesions (0.05 per 100 person-years).9

The follow-up testing of a pituitary incidentaloma is different for microincidentaloma and macroincidentaloma. For macroincidentaloma, pituitary MRI with clinical and biochemical testing for hypopituitarism should be completed at 6 months after the initial diagnosis and then yearly for several years, with visual field assessment if the tumor enlarges to abut or compress the optic nerves or chiasm. For microincidentaloma, MRI should be performed at 12 months after the initial diagnosis, but there is no need to test for hypopituitarism if there was no change in the clinical and radiographic features.1

Surgical intervention should be recommended for cases of hypersecreting tumors other than prolactinomas, pituitary apoplexy with visual disturbances, lesions abutting or compressing the optic nerves or chiasm on MRI, or in the presence of visual field deficit or other visual abnormalities due to the lesion.1 Surgical resection of nonfunctioning microadenomas is not indicated as tumor growth is rare, with less than 5% growing significantly during long-term follow-up.6

Medical treatment for pituitary incidentaloma may include dopamine agonist therapy for patients with prolactinoma. In some cases of pituitary incidentaloma, somatostatin analogues may be used, but there are limited data on the use of medical therapy for these tumors.1

References

1. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(4):894-904.

2. Bevan JS. Pituitary incidentaloma. Clin Med J R Coll Physicians London. 2013;13(3):296-298.

3. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101(3):613-619.

4. Scangas GA, Laws ER. Pituitary incidentalomas. Pituitary. 2014;17(5):486-491.

5. Boguszewski CL, de Castro Musolino NR, Kasuki L. Management of pituitary incidentaloma. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101268.

6. Esposito D, Olsson DS, Ragnarsson O, Buchfelder M, Skoglund T, Johannsson G. Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management. Pituitary. 2019;22(4):422-434.

7. Imran SA, Yip C-E, Papneja N, et al. Analysis and natural history of pituitary incidentalomas. Eur J Endocrinol. 2016;175(1):1-9.

8. Souteiro P, Maia R, Santos-Silva R, et al. Pituitary incidentalomas in paediatric age are different from those described in adulthood. Pituitary. 2019;22(2):124-128.

9. Fernndez-Balsells MM, Murad MH, Barwise A, et al. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2011;96(4):905-912.

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Diagnosis and Management of Pituitary Incidentaloma - Endocrinology Advisor

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