The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Jan 1998
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialThe Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults.
GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of < 5 mU/liter in response to insulin-induced hypoglycemia. ⋯ Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-density lipoprotein cholesterol, together with substantial reductions in total-body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggests that lower doses of GH may be a required for prolonged GH treatment in adults with severe GH deficiency.
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J. Clin. Endocrinol. Metab. · Jan 1998
Randomized Controlled Trial Clinical TrialEffects of therapy with recombinant human growth hormone on insulin-like growth factor system components and serum levels of biochemical markers of bone formation in children after severe burn injury.
Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone fomation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg.day) or an equal volume of saline. ⋯ Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.
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J. Clin. Endocrinol. Metab. · Jan 1998
Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion.
Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. ⋯ In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.
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J. Clin. Endocrinol. Metab. · Jan 1998
Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals.
In the present study, we investigated whether the negative feedback action of glucocorticoids (GCs) on the hypothalamo-pituitary-adrenal (HPA) axis changes with age. We performed a 1-mg dexamethasone (DEX) suppression test in 216 healthy elderly individuals. To investigate individual variability of feedback sensitivity in more detail, 2.5 yr later a 0.25-mg DEX suppression test was carried out in 164 of the same individuals. ⋯ Aging does not seem to lead to a change in HPA activity as measured by early morning total cortisol levels. Also, no changes in the sensitivity of the feedback system to DEX were observed with age. DEX metabolism is influenced by liver function (in males) and by body mass index (in females).