R. C. Cuneo

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.

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)

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.

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.