Males with prolactin-secreting tumors rarely have galactorrhea and usually present with a larger tumor and complaints such as headache, impotence, and visual abnormalities. In normal persons, the serum prolactin rises markedly in response to the administration of chlorpromazine or thyrotropin-releasing hormone (TRH); patients with a prolactin-secreting tumor fail to show such a response. With large tumors that compress normal pituitary tissue, thyroid and adrenal function will also be impaired. It should be emphasized that large, nonfunctioning pituitary adenomas also cause modest hyperprolactinemia by distorting the pituitary stalk and reducing dopamine delivery to prolactin-producing cells.
Acromegaly This disorder consists of acral growth and prognathism in combination with visceromegaly, headache, and several endocrine disorders (hypermetabolism, diabetes mellitus). The highly characteristic facial and bodily appearance, well known to all physicians, is caused by an overproduction of GH after puberty; prior to puberty, an oversecretion of GH leads to gigantism. In a small number of acromegalic patients, there is an excess secretion of both GH and prolactin, derived apparently from two distinct populations of tumor cells. The diagnosis of this disorder, which is often long delayed, is made on the basis of the characteristic clinical changes, the finding of elevated serum GH values (0.10 ng/mL), and the failure of the serum GH concentration to decline in response to the administration of glucose or TRH. The new growth hormone-receptor antagonist pegvisomant was introduced to reduce many of the manifestations of acromegaly (see the review by Melmed).
Cushing disease Described in 1932 by Cushing, this condition is only about one-fourth as frequent as acromegaly. A distinction is made between Cushing disease and Cushing syndrome, as indicated in Chap. 26. The former term is reserved for cases that are caused by the excessive secretion of pituitary ACTH, which, in turn, causes adrenal hyperplasia; the usual basis is a pituitary adenoma. Cushing syndrome refers to the effects of cortisol excess from any one of several sources—excessive administration of steroids (the most common cause), adenoma of the adrenal cortex, ACTH-producing bronchial carcinoma, and, very rarely, other carcinomas that produce ACTH. The clinical effects are the same in all of these disorders and include truncal obesity, hypertension, proximal muscle weakness, amenorrhea, hirsutism, abdominal striae, hyperglycemia, osteoporosis, and in some cases a characteristic mental disorder (see “Cushing Disease and Corticosteroid Psychoses” in Chap. 49).
Although Cushing originally referred to the disease as pituitary basophilism and attributed it to a basophil adenoma, the pathologic change may consist only of hyperplasia of basophilic cells or of a nonbasophilic microadenoma. Seldom is the sella turcica enlarged: Consequently, visual symptoms or signs as a result of involvement of the optic chiasm or nerves and extension to the cavernous sinus are rare. The diagnosis of Cushing disease is made by demonstrating increased concentration of plasma and urinary cortisol; these levels are not suppressed by the administration of relatively small doses of dexamethasone (0.5 mg qid), but they are suppressed by high doses (8 mg daily). A low level of ACTH and a high level of cortisol in the blood, increased free cortisol in the urine, and nonsuppression of adrenal function after administration of high doses of dexamethasone are evidence of an adrenal source of the Cushing syndrome—usually a tumor and less often a micronodular hyperplasia of the adrenal gland.