In an accompanying paper (1) human growth hormo.ne (HGH) was reported to have stimulated the rate of linear growth, produced retention of nitrogen, phosphorus, magnesium, calcium, sodium and potassium, and perhaps increased the rate of fat mobilization in ten human subjects. This paper describes the response of blood and urinary levels of fat and carbohydrate intermediary metabolites in seven of these and in one infant with hyperinsulinism.1 Some effects of HGH on carbohydrate and fat metabolism have already been published. Raben and Hollenberg (2) observed a prompt and significant rise in plasma free fatty acids (FFA). Beck, McGarry, Dyrenfurth and Venning (3) reported alterations in glucose tolerance in four of six patients and Ikkos, Luft and Gemzell (4) in two of two patients. Ikkos and associates also observed elevations in ketone bodies in three of four patients. The data to be reported in general confirm these observations and include the simultaneous measurements of blood and urinary glucose, lactate, pyruvate, citrate, a-ketoglutarate, free fatty acids and ketones during short and longterm HGH therapy.
MATERIAL AND METHODSThe clinical features of the patients studied are reported elsewhere (1). The subjects include 5 patients with hypopituitarism, 1 patient with obesity on an 800 calorie diet and 1 patient with proven hyperinsulinism (5). All patients were studied under constant conditions.Blood levels of carbohydrate and fat intermediary metabolites were measured 4, 8 and 24 hours after injections of 1.0 to 10.0 mg of acid-soluble HGH (Raben).2 HGH was administered as a single intramuscular injection at 6 a.m. (or beginning of "metabolic day") daily for 2 to 36 days.The methods for measurement of blood and urinary glucose, lactic, pyruvic, a-ketoglutaric and citric acids, acetone and total ketones, and inorganic phosphorus have been reported previously (6). In addition, plasma FFA were measured by the method of Davis (7) as modified by Gordon and Cherkes (8). Balance studies were conducted according to the method of Reifenstein, Albright and Wells (9). RESULTS HGH (1) produced a decrease in blood urea nitrogen (BUN) and urinary nitrogen in 24 to 48 hours which was not apparent within the first four hours after injection. With constant daily HGH injections, nitrogen retention increased for 3 to 5 days, was maximal for 2 weeks, and then decreased to low levels in the fourth and fifth weeks of treatment. If HGH were discontinued for 12 days and then resumed, nitrogen retention was again marked. Other constituents of protoplasm were retained in the relative concentrations characteristic of most tissues.Because of the multiphasic nature of the nitrogen response to HGH the measurements of intermediary metabolites have been separated as follows: the early phase (4 hours to 3 days), as nitrogen retention is developing; the second phase (3 to 15 days) during sustained maximal nitrogen 2 Similar responses were obtained with a procainehydrochloride precipitate of HGH (Raben) (1). This preparation of procaine was ...