Growth Hormone

Growth hormone, or somatotropin, is a protein that stimulates linear body growth in children and regulates cellular metabolism in both adults and children. Growth hormone stimulates lipolysis, enhances production of free fatty acids, elevates blood glucose, and promotes positive nitrogen balance. Many of its anabolic actions are mediated by enhanced production of an insulinlike growth factor (IGF-1), a protein produced in many tissues in response to growth hormone.

The episodic release of growth hormone is the most pronounced among the pituitary hormones. Serum levels between bursts of release are usually low (<5

ng/mL) and increase more than 10-fold when release is elevated. The marked variation in serum levels is in part the result of strong controls in opposite directions by the hypothalamic hormones, growth hormone-releasing hormone (GHRH), and somatostatin. Circulating factors, such as IGF-1 and ghrelin, a peptide produced in large amounts in neuroendocrine cells of the stomach, also affect growth hormone secretion. Growth hormone is released during sleep, with maximum release occurring an hour after the onset of sleep. Growth hormone is also released after exercise, by hypoglycemia, and in response to arginine and levodopa.

Growth Hormone Deficiency

Growth hormone deficiency in children results in short stature and in adults increases fat mass and reduces muscle mass, energy, and bone density. Measurements of serum growth hormone levels are used for diagnosis of deficiency, but random measurements are not useful, because normal episodic release results in large variations in growth hormone levels. Growth hormone deficiency is most convincingly demonstrated by lack of response to provocative stimuli, such as administration of insulin, levodopa, or arginine. Recently a combination of GHRH and ghrelin have been used and have given large responses in normal subjects. Deficiencies are corrected by giving human growth hormone. Growth hormone is also sometimes given to individuals who are not growth hormone-deficient; it is used to increase the height of girls with Turner's syndrome and in certain conditions to counteract the wasting that may occur in AIDS.

In the past human growth hormone was prepared from human pituitary glands, but this source was discontinued after people who had received treatment contracted Creutzfeldt-Jakob disease. Now two forms of recombinant human growth hormone are available: somatropin (Humatrope and others), which has the same amino acid sequence as pituitary-derived growth hormone, and somatrem (Protropin), which has an N-terminal methionine that the pituitary form does not. Subcutaneous injections each evening, which mimic the natural surge that occurs at the start of sleep, are the usual regimen. Stimulation of growth in children is most effective when treatment begins early.

Growth Hormone Excess

Acromegaly results from chronic secretion of excess growth hormone, usually as a result of pituitary adenoma. Long bones will not grow in adults because the epiphyses are closed, but bones of the extremities (hands, feet, jaw, and nose) will enlarge. The skin and soft tissues thicken, and the viscera enlarge. Excessive growth hormone secretion is demonstrated by elevated serum levels of growth hormone after glucose administration, since glucose is less effective in inhibiting growth hormone secretion in acromegalics than it is in normal subjects. In addition, serum IGF-1 levels are elevated in acromegalics.

The primary treatment of acromegaly is surgery. Pharmacotherapy is used when surgical treatment is not successful. Two dopamine agonists (see Chapter 31), bromocriptine and cabergoline, are sometimes effective; they are taken orally. Although dopamine stimulates growth hormone release in normal individuals, it inhibits growth hormone release in up to 50% of acromegalics. The somatostatin analogue octreotide is usually more effective, and now that a long-acting form is available that requires only monthly injections, it is the preferred treatment. Another possible growth hormone antagonist, pegvisomant, is being investigated.

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