Hypopituitarism (Panhypopituitarism): Background …

Posted: November 28, 2016 at 5:42 am

Causes of pituitary insufficiency include pituitary adenomas or other intrasellar and parasellar tumors, inflammatory and infectious destruction, surgical removal, radiation-induced destruction of pituitary tissue, traumatic brain injury (TBI), subarachnoid hemorrhage, and postpartum pituitary necrosis (Sheehan syndrome). Similar diseases originating in the hypothalamus or pituitary stalk may also result in pituitary insufficiency.

Pituitary tumors, or adenomas, are the most common cause of hypopituitarism in adults, although traumatic brain injury as a cause is being more frequently recognized.

Hypopituitarism resulting from pituitary adenomas is due to impaired blood flow to the normal tissue, compression of normal tissue, or interference with the delivery of hypothalamic hormones via the hypothalamus-hypophysial portal system.

In primary pituitary destruction, the anterior pituitary is destroyed, causing a deficiency in some or all pituitary hormones, including prolactin. Disease involving the hypothalamus or pituitary stalk may cause pituitary hormone deficiency with an elevated serum prolactin. Pituitary tumors, or adenomas, can be secretory or nonsecretory. Approximately 30% of all macroadenomas larger than 10 mm produce at least 1 hormone.

Hypothalamic disease involves destruction of the hypothalamus. This causes a deficiency or loss of hypothalamic regulatory hormone input to the pituitary, which leads to the loss of anterior pituitary hormone secretion, with an elevated serum prolactin level. Loss of antidiuretic hormone (ADH) may have concomitant diabetes insipidus.

Hypersecretion of the secretory pituitary tumor hormone is suggestive of an adenoma. Another indication of a pituitary adenoma is a deficiency in some pituitary hormones with concomitant hyperprolactinemia. Normally, dopamine, produced in the hypothalamus, inhibits prolactin secretion by the anterior pituitary. Compressing the pituitary stalk decreases the inhibitory effect of dopamine and increases prolactin levels.

Longstanding target gland disease may result in hyperplasia of the relevant pituitary cell secreting the tropic hormone, the level of which would be elevated, with an enlarged pituitary gland simulating a mass. Although uncommon, this may appear to be a pituitary adenoma, but the target gland is not hyperfunctioning.

Another common intracranial tumor is craniopharyngioma, a squamous cell tumor that arises from remnants of the Rathke pouch. One third of these tumors extend into the sella, while approximately two thirds remain suprasellar.

Sheehan syndrome occurs with a large volume of postpartum hemorrhage. During pregnancy, the pituitary gland enlarges due to hyperplasia and hypertrophy of the lactotroph cells, which produce prolactin. The hypophyseal vessels, which supply the pituitary, constrict in response to decreasing blood volume, and subsequent vasospasm occurs, causing necrosis of the pituitary gland. The degree of necrosis correlates with the severity of the hemorrhage.

As many as 30% of women experiencing postpartum hemorrhage with hemodynamic instability may develop some degree of hypopituitarism. These patients can develop adrenal insufficiency, hypothyroidism, amenorrhea, diabetes insipidus, and an inability to breastfeed (an early symptom). Lymphocytic hypophysitis occurs most commonly in the postpartum state and may appear as Sheehan syndrome with postpartum hypopituitarism.

Pituitary apoplexy denotes the sudden destruction of the pituitary tissue resulting from infarction or hemorrhage into the pituitary. The most likely cause of the apoplexy is brain trauma; however, it can occur in patients with diabetes mellitus, pregnancy, sickle cell anemia, blood dyscrasias or anticoagulation, or increased intracranial pressure. Apoplexy usually spares the posterior pituitary and solely affects the anterior pituitary. In patients with such underlying diseases, Sheehan syndrome can occur with lesser degrees of postpartum hemorrhage or hypotension.

Head trauma from a motor vehicle accident, a fall, or a projectile can cause hypopituitarism by direct damage to the pituitary or by injuring the pituitary stalk or the hypothalamus. Hypopituitarism may occur immediately, or it may develop months or years later. Recovery is uncommon. Many studies show an incidence of 15-40%, [2] but a study by Kokshoorn et al found the incidence of posttraumatic hypopituitarism to be low. [3]

Other causes of hypopituitarism include empty sella syndrome and infiltrative diseases. Empty sella syndrome occurs when the arachnoid herniates into the sella turcica through an incompetent sellar diaphragm and flattens the pituitary against bone, but resulting pituitary insufficiency is uncommon. Infiltrative diseases, such as Wegener granulomatosis and sarcoidosis, can cause destruction of the anterior pituitary. Lymphocytic hypophysitis is an autoimmune destructive disease that may be directed towards the pituitary or its stalk.

Physiologic or psychological states can influence the hypothalamus by impairing synthesis and secretion of regulating hormones. For example, poor nutrition may impair the hypothalamic secretion of gonadotropin-releasing hormone (GnRH), resulting in reversible pituitary gonadotropin deficiency. Medications may affect measured hormone levels, such as opioids decreasing serum LH and testosterone.

The degree of hormone deficiency varies greatly and depends on the extent of the process and its location. Some functional causes include emotional disorders, changes in body weight, habitual exercise, anorexia, bulimia, congestive heart failure (CHF), renal failure, and certain medications.

Hypopituitarism occurs in adult patients after cranial radiotherapy performed to treat nonpituitary tumors. Thus, patients who undergo cranial radiotherapy should be periodically assessed for pituitary functions. [4]

Additional causes of hypopituitarism include the following:

With regard to item 9 above, in a study of 435 patients, Fatemi et al found evidence that the likelihood of hypopituitarism development after transsphenoidal adenoma removal is higher when the tumor is larger than 20 mm. [6] In contrast, some with hypopituitarism prior to adenomectomy may have improved pituitary function following surgery, if the cause of the hypopituitarism was increased suprasellar pressure resulting from the mass itself.

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