Hypopituitarism

Acquired Hypopituitarism

Inflammatory Lesions

Pituitary damage and subsequent dysfunction can be seen with chronic infections such as tuberculosis, with opportunistic fungal infections associated with AIDS, and in tertiary syphilis. Other inflammatory processes, such as granulomas or sarcoidosis, may mimic the features of a pituitary adenoma. These lesions may cause extensive hypothalamic and pituitary damage, leading to trophic hormone deficiencies.

Cranial Irradiation

Cranial irradiation may result in long-term hypothalamic and pituitary dysfunction, especially in children and adolescents, as they are more susceptible to damage following whole-brain or head and neck therapeutic irradiation. The development of hormonal abnormalities correlates strongly with irradiation dosage and the time interval after completion of radiotherapy. Up to two-thirds of patients ultimately develop hormone insufficiency after a median dose of 50 Gy (5000 rad) directed at the skull base. The development of hypopituitarism occurs over 5–15 years and usually reflects hypothalamic damage rather than primary destruction of pituitary cells. Although the pattern of hormone loss is variable, GH deficiency is most common, followed by gonadotropin and ACTH deficiency. When deficiency of one or more hormones is documented, the possibility of diminished reserve of other hormones is likely. Accordingly, anterior pituitary function should be evaluated over the long term in previously irradiated patients, and replacement therapy instituted when appropriate (see below).

Lymphocytic Hypophysitis

This often occurs in postpartum women; it usually presents with hyperprolactinemia and MRI evidence of a prominent pituitary mass often resembling an adenoma, with mildly elevated PRL levels. Pituitary failure caused by diffuse lymphocytic infiltration may be transient or permanent but requires immediate evaluation and treatment. Rarely, isolated pituitary hormone deficiencies have been described, suggesting a selective autoimmune process targeted to specific cell types. Most patients manifest symptoms of progressive mass effects with headache and visual disturbance. The erythrocyte sedimentation rate is often elevated. As the MRI image may be indistinguishable from that of a pituitary adenoma, hypophysitis should be considered in a postpartum woman with a newly diagnosed pituitary mass before embarking on unnecessary surgical intervention. The inflammatory process often resolves after several months of glucocorticoid treatment, and pituitary function may be restored, depending on the extent of damage.

Pituitary Apoplexy

Acute intrapituitary hemorrhagic vascular events can cause substantial damage to the pituitary and surrounding sellar structures. Pituitary apoplexy may occur spontaneously in a preexisting adenoma; post-partum (Sheehan's syndrome); or in association with diabetes, hypertension, sickle cell anemia, or acute shock. The hyperplastic enlargement of the pituitary during pregnancy increases the risk for hemorrhage and infarction. Apoplexy is an endocrine emergency that may result in severe hypoglycemia, hypotension, central nervous system (CNS) hemorrhage, and death. Acute symptoms may include severe headache with signs of meningeal irritation, bilateral visual changes, ophthalmoplegia, and, in severe cases, cardiovascular collapse and loss of consciousness. Pituitary computed tomography (CT) or MRI may reveal signs of intratumoral or sellar hemorrhage, with deviation of the pituitary stalk and compression of pituitary tissue.

Empty Sella

A partial or apparently totally empty sella is often an incidental MRI finding. These patients usually have normal pituitary function, implying that the surrounding rim of pituitary tissue is fully functional. Hypopituitarism, however, may develop insidiously. Pituitary masses may undergo clinically silent infarction with development of a partial or totally empty sella by cerebrospinal fluid (CSF) filling the dural herniation. Rarely, small but functional pituitary adenomas may arise within the rim of pituitary tissue, and these are not always visible on MRI

For example, low free thyroxine in the setting of a low or inappropriately normal TSH level suggests secondary hypothyroidism. Similarly, a low testosterone level without elevation of gonadotropins suggests hypogonadotropic hypogonadism. Provocative tests may be required to assess pituitary reserve (Table 333-3). GH responses to insulin-induced hypoglycemia, arginine, L-dopa, growth hormone–releasing hormone (GHRH), or growth hormone–releasing peptides (GHRPs) can be used to assess GH reserve. Corticotropin-releasing hormone (CRH)

administration induces ACTH release, and administration of synthetic ACTH (cortrosyn) evokes adrenal cortisol release as an indirect indicator of pituitary ACTH reserve (Chap. 336). ACTH reserve is most reliably assessed during insulin-induced hypoglycemia. However, this test should be performed cautiously in patients with suspected adrenal insufficiency because of enhanced susceptibility to hypoglycemia and hypotension. Insulin-induced hypoglycemia is contraindicated in patients with active coronary artery disease or seizure disorders

Hormone production does not always correlate with tumor size. Small hormone-secreting adenomas may cause significant clinical perturbations, whereas larger adenomas that produce less hormone may be clinically silent and remain undiagnosed (if no central compressive effects occur). About one-third of all adenomas are clinically nonfunctioning and produce no distinct clinical hypersecretory syndrome.