Franco Salomon

The Effects of Treatment with Recombinant Human Growth Hormone on Body Composition and Metabolism in Adults with Growth Hormone Deficiency

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.

The growth hormone deficiency syndrome in adults

The effects of growth hormone (GH) deficiency in childhood are well recognized. These include shortness of stature with normal proportions, slow linear growth rate, delayed bone age with reduced bone density, excess adiposity with a predominantly truncal distribution, reduced lean tissue mass, and fasting hypoglycaemia (Collip et al., 1973; Hopwood et al., 1975; Tanner et al., 1977; Milner et al., 1979; Parra et al., 1979, Shore et al., 1980). These effects reflect the known metabolic actions of GH (Davidson, 1987; Press, 1988); GH promotes anabolism and lipolysis, and has complex actions on carbohydrate metabolism which can be summarized as insulinotrophic and insulin antagonistic. The effects of GH deficiency in adults have been appreciated only recently. There may be several reasons for this. Firstly, adults who developed panhypopituitarism from mass effects of a pituitary tumour or the treatment of the tumour survived, often returning to reasonably functional lives with conventional pituitary hormone replacement therapy. Secondly, GH treatment of such patients was not possible due to limited supplies of human pituitary-derived GH. The introduction of recombinant DNA technology has resulted in the production of authentic sequence human GH (rhGH) in potentially unlimited supplies, allowing treatment of conditions other than short stature. The aims of this review are to summarize the recent studies of GH treatment in adults with GH deficiency, thereby defining the syndrome of GH deficiency in adults, and to highlight areas for future investigation.

Skeletal Muscle Performance in Adults with Growth Hormone Deficiency

Skeletal muscle mass and function were assessed in 24 adults (16 males, 8 females) with severe, long-standing GH deficiency. Compared to 41 untrained controls (26 males, 15 females), adults with GH deficiency had reduced cross-sectional area of thigh muscle/body weight (p = 0.01), reduced quadriceps force/weight (males: p = 0.002; females: p less than 0.0001), and reduced quadriceps force/muscle area (males: p = 0.005). This suggests (a) that adults with GH deficiency have reduced skeletal muscle mass due, in part, to the absence of the anabolic effects of GH, and (b) that skeletal muscle force may be reduced due to altered muscle mass, contractile elements/muscle fibre, anaerobic energy supply, neural recruitment of fibres, or a combination of these.

Histology of skeletal muscle in adults with GH deficiency : comparison with normal muscle and response to GH treatment

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic Effects of Hypopituitarism and Acromegaly1

Hypopituitarism is associated with reduced lean body mass and increased body fat, while in acromegaly the converse is true. Fasting plasma glucose is increased in acromegaly but fasting plasma insulin

Glucose and fat metabolism in adults with growth hormone deficiency.

OBJECTIVE Adults with long‐standing GH deficiency have a decreased lean body mass and an increased fat mass. We investigated the effects of the abnormal body composition on glucose turnover and fuel metabolism.

Symptomatic Hypoparathyroidism in Acquired Immunodeficiency Syndrome

Involvement of endocrine organs is frequent in patients with HIV infections. We report the first case of symptomatic hypoparathyroidism in a patient in the course of HIV infection. He presented with tetany and hypocalcemia in the presence of decreased levels of parathyroid hormone, which persisted after correction of hypomagnesemia. The family history was negative and none of the autoimmune diseases associated with hypoparathyroidism was present. No local destruction by tumor or infection could be demonstrated apart from HIV infection. We propose a causal role of HIV infection in the development of hypoparathyroidism and discuss the possible mechanisms of parathyroid involvement in AIDS.

Glucose metabolism in adults with growth hormone deficiency.

Adults with GHD have normal overnight fasting glucose levels and normal overall glucose turnover. In the absence of GH, insulin secretion is reduced and may be associated with impaired glucose tolerance. The lack of GH is associated with normal insulin sensitivity but reduced hypoglycaemic responsiveness, probably due to a reduced supply of gluconeogenic substrates. When GHD is associated with obesity, however, hyperinsulinaemia and insulin resistance ensue and hypoglycaemic responsiveness is restored. In adults with GHD, treatment with recombinant human GH for 6 months increased fasting plasma glucose to within the normal range, with no change in overall glucose turnover and carbohydrate tolerance, in the presence of elevated basal insulin levels.

Growth Hormone Treatment in Adults with Growth Hormone Deficiency

As a clinical entity, growth hormone (GH) deficiency in adulthood has previously received little attention. This has been due in part to a traditional view that GH is only of physiological importance during childhood and adolescence, when its effects are most visible and dramatic, despite the fact that GH secretion normally continues throughout adult life. More importantly, the limited availability of pituitary-derived human GH in the past meant there was no possibility of exploring its effects in GH-deficient adults. This problem has been overcome with the introduction of recombinant human GH, in potentially unlimited quantities.