Growth hormone–secreting somatotroph adenomas are the second most common type of functioning pituitary adenoma, and cause gigantism in children or acromegaly in adults. Because the clinical manifestations of excess growth hormone may be subtle, somatotroph cell adenomas may be quite large by the time they come to clinical attention. On microscopic examination, growth hormone– producing adenomas are composed of densely or sparsely granulated cells, and immunohistochemical staining demonstrates growth hormone within the cytoplasm of the neoplastic cells. Small amounts of immunoreactive prolactin often are present as well.
Persistent growth hormone excess stimulates the hepatic secretion of insulin-like growth factor 1 (IGF1), which acts in conjunction with growth hormone to induce overgrowth of bones and muscle. If a growth hormone– secreting adenoma develops before the epiphyses close, as is the case in prepubertal children, excessive levels of growth hormone and IGF1 result in gigantism. This condition is characterized by a generalized increase in body size, with disproportionately long arms and legs. If elevated levels of growth hormone and IGF1 persist or develop after closure of the epiphyses, affected individuals develop acromegaly, in which growth is most conspicuous in soft tissues, skin, viscera, and the bones of the face, hands, and feet. Enlargement of the jaw results in its protrusion (prognathism), broadening of the lower face, and separation of the teeth. The hands and feet are enlarged, and the fingers are broad and sausage-like. In most instances gigantism is accompanied by evidence of acromegaly. These changes may develop slowly over decades before being recognized, hence the adenoma may be quite large before it is detected.
Persistent growth hormone excess also is associated with metabolic abnormalities, the most important of which is diabetes mellitus. This arises because of growth hormone–induced peripheral insulin resistance, which “blunts” the body’s response to elevated glucose levels (see “ ”, later). Failure to suppress growth hormone production in response to an oral load of glucose is one of the most sensitive tests for acromegaly. Other manifestations of growth hormone excess include gonadal dysfunction, generalized muscle weakness, hypertension, arthritis, congestive heart failure, and an increased risk for gastrointestinal cancers.
http://ebooksmedicine.net
Excess production of ACTH by functioning corticotroph adenomas leads to adrenal hypersecretion of cortisol and the development of hypercortisolism (also known as Cushing syndrome). Cushing syndrome (discussed later with diseases of the adrenal gland) may be caused by other conditions as well. When the hypercortisolism is caused by excessive production of ACTH by the pituitary, it is called Cushing disease after the neurosurgeon Harvey Cushing who first described the disorder.
Most corticotroph adenomas are small (microadenomas) at the time of diagnosis. These adenomas stain positively with periodic acid–Schiff (PAS) stains, as a result of the accumulation of glycosylated ACTH protein. ACTH also can be specifically detected by immunohistochemical methods. Large, clinically aggressive corticotroph cell adenomas may develop after surgical removal of the adrenal glands for treatment of Cushing syndrome. In most instances this condition, known as Nelson syndrome, results from loss of the inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma. Because the adrenals are absent in individuals with Nelson syndrome, hypercortisolism does not develop. Instead, patients present with the mass effects of the pituitary tumor. Patients with Cushing syndrome often have hyperpigmented skin because of increased production of melanocyte stimulating hormone (MSH), which is derived from the same precursor as ACTH so its synthesis accompanies that of ACTH.