The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition.

OBJECTIVE: The effect on bone, protein, carbohydrate and lipid homeostasis as well as body composition of the administration of growth hormone to adult patients with growth hormone deficiency was studied. DESIGN: Growth hormone was administered at a dose of 25 micrograms/kg/day with a maximum of 1.48 mg (4 IU) a day, for 6 months in eight adults. Studies were done before the start and at 1, 3 and 6 months during therapy, as well as 3 months after treatment had been stopped. RESULTS: Subjective well-being as assessed by a short psychological tests showed an improvement in six and no change in two patients. Body composition, as assessed by body impedance assessment and D2O dilution, both showed an increase in lean body mass of 4 kg (5% of body weight), accompanied by a decrease in mean fat mass of 3 kg. Nitrogen turnover studies showed a transient increase in fed state nitrogen balance due to an increase in the rate of protein synthesis, which exceeded a smaller increase in the protein degradation rate. Growth hormone treatment did not affect the circulating levels of 25(OH)-vitD or PTH 1-84, while 1,25(OH)2-vitD had significantly increased after 6 months, as well as 3 months after treatment ended. Osteocalcin, procollagen I levels, as well as 24-hour urinary excretion of hydroxyproline and calcium rose during growth hormone administration but subsequently decreased rapidly after administration had been stopped, while the increase in alkaline phosphatase persisted. This increase in markers of both bone resorption and bone formation indicates an activation of bone remodelling, but this was not reflected by an increase in bone density. Glucose levels, measured before and during a normal breakfast, increased during growth hormone treatment, but serum insulin levels did not. Total cholesterol levels decreased by 0.5 mmol/l. Levels of T4 and free T4 as well as rT3 decreased, while T3 increased during growth hormone treatment. CONCLUSION: Therapy with growth hormone for 6 months in a dose varying between 6 and 25 micrograms/kg/day increased lean body mass and decreased fat mass. The sense of general well-being improved in most patients. Furthermore, growth hormone treatment increased bone turnover without a measurable increase in bone density, caused some minor changes in lipid and carbohydrate metabolism, and increased the metabolism of thyroxine to T3.

Body composition in growth hormone-deficient adults.

Body composition in a group of growth hormone (GH)-deficient adults was compared with a control group matched for age, sex, body height, body weight, and body mass index by using bioelectrical impedance and deuterium oxide-dilution methods and hydrodensitometry. The body-fat percentages of GH-deficient adults were higher despite comparable weight, height, age, and body mass index. Body impedance was higher in the GH-deficient adults after correction for differences in height and fat-free mass. As a consequence, prediction formulas for body composition from body impedance developed in normal subjects cannot be applied to GH-deficient subjects. The higher body impedance in the GH-deficient subjects can be ascribed to a smaller amount of extracellular water in these subjects than in control subjects.

The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b).

The direct effects of human GH and IGF-I on PRL secretion and cell proliferation were studied on PRL secreting rat pituitary tumor 7315b cells in vitro, as well as the effects in vivo of human GH administration on body weight, IGF-I levels and tumor size in rats bearing this transplantable tumor. In the in vitro studies IGF-I levels above 5 nM stimulated PRL release in a dose-dependent manner while GH, in concentrations of 0.23-45 nM, did not affect PRL release. Cell proliferation was stimulated by IGF-I in a dose-dependent manner from 0.5 nM onwards, while GH did not have an effect. The in vivo studies showed that 1 mg GH/rat/day prevented tumor-induced cachexia and normalized the suppressed IGF-I levels without stimulating tumor growth. It is concluded that tumor-induced cachexia can be prevented by exogenous GH administration without an increase in tumor mass, even if a tumor model is used whose cultured tumor cells respond to exposure to IGF-I with a mitotic response.

The effects of human growth hormone administration in elderly adults with recent weight loss.

The effects of human GH administration in elderly adults with recent weight loss were investigated in a metabolic ward study. Four patients were studied for 20 days. In addition to a constant caloric and nitrogen-sufficient diet, consisting of the recommended amounts of protein and energy plus 20%, the patients received GH in dosages of 25 and 50 micrograms/kg.day for two 4-day periods (days 5-8 and 13-16, respectively). Significant increases in nitrogen retention of 1.6 (114.2) and 1.4 g/day (100 mmol/day), respectively, occurred compared with that in the control periods. No difference was found between the two GH dosages, but the nitrogen-retaining effect of the higher dose appeared to last for several days after its administration was stopped. Plasma insulin-like growth factor I levels rose during both treatment periods. No important disturbances in carbohydrate metabolism occurred. Body weight increased 2.3 kg during each treatment period, probably due to water retention. We conclude that even during more than adequate nutritional intake, low GH doses cause considerable nitrogen retention in underweight adults.

Regulation of hemoglobin AIc formation in human erythrocytes in vitro. Effects of physiologic factors other than glucose.

The formation of hemoglobin AIc was studied in intact human erythrocytes in vitro. Satisfactory methods were developed for maintaining erythrocytes under physiologic conditions for greater than 8 d with less than 10% hemolysis. Hemoglobin AIc levels were determined chromatographically on erythrocyte hemolysates after removal of reversible components by incubation for 6 h at 37 degree C. Hemoglobin AIc concentration was found to increase linearly with time during 8 d of incubation. The rate of formation of hemoglobin AIc increased linearly as glucose concentration was increased from 40 to 1,000 mg/dl. Deoxyhemoglobin was glycosylated twice as rapidly as oxyhemoglobin. The rate of hemoglobin AIc formation was further increased by elevated 2,3-diphosphoglycerate levels, an effect that was most marked with deoxyhemoglobin. We conclude that the nonenzymatic glycosylation of hemoglobin is influenced by factors other than glucose, including oxygen tension and 2,3-diphosphoglycerate levels.