Human growth hormone: Metabolic effects and experimental and therapeutic applications

Abstract

Injections of human growth hormone into man almost uniformly cause significant nitrogen retention, indicative of an anabolic effect on protein metabolism. In patients with diabetes mellitus the administration of human growth hormone may produce little or no nitrogen retention, possibly indicating that insulin is required for the anabolic effect of the hormone. Although unessential for the anabolic activities of human growth hormone, thyroid secretion may exert a synergistic effect. A 5 or 10 mg. dose of human growth hormone appears to produce the maximum effect on nitrogen metabolism. Human growth hormone administration is followed by a decrease in blood urea nitrogen and a retention of phosphorus and potassium and, in some cases, calcium. Hypercalciuria usually occurs after the administration of human growth hormone, but, depending upon the effect on fecal calcium, there may result a negative or positive calcium balance, or no significant change. Sodium and chloride retention, and an increase in extracellular fluid volume with resultant weight gain and, occasionally, manifest edema, are noted following injections of human growth hormone. The effect on sodium apparently is not mediated through changes in aldosterone output. Exogenous human growth hormone exerts a diabetogenic effect, manifested most commonly by an impairment in glucose tolerance. Insulin resistance, a rise in blood sugar and glycosuria may also be noted. Administration of human growth hormone is regularly and rapidly followed by a rise in plasma non-esterified fatty acids and ketones. Ketonuria and an increase in serum and urinary citrate may also occur. Patients with diabetes are particularly sensitive to the effects produced by human growth hormone on fat and carbohydrate metabolism. The effect, if any, of human growth hormone on cholesterol metabolism cannot be stated with certainty from the available data. The therapeutic use of human growth hormone has been limited thus far to the stimulation of linear growth in hypopituitary dwarfs. Experimentally, the preparation has been administered to patients with diabetes insipidus, chronic renal disease and chronic hepatic disease. Untoward effects of human growth hormone administration include oliguria, nervousness, headache, tachycardia, nausea and anorexia. Except for the last, these are uncommonly observed. Increased sweating is frequent. Generalized allergic reactions have not been seen. The results of immunologic assay for the presence of human growth hormone in serum, and of the determination of sulfation factor activity in serum (a reflection of human growth hormone output) are summarized.