Context:Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute cortisol deficiency.Objective: The objective of the study was to test whether clinical symptoms of weight loss, fatigue, and hypoglycemia could be explained by altered energy expenditure, protein metabolism, and insulin sensitivity during cortisol withdrawal in adrenocortical failure.Design, Participants, and Intervention: We studied seven women after 24-h cortisol withdrawal and during replacement control during a 3-h basal period and a 3-h glucose clamp.Results: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in basal energy expenditure, increased TSH and T 3 levels, and increased glucose oxidation. Whole-body glucose and phenylalanine turnover were unaltered, but forearm phenylalanine turnover was increased. During the clamp glucose, infusion rates rose by 70%, glucose oxidation rates increased, and endogenous glucose production decreased. Urinary urea excretion decreased by 40% over the 6-h study period.
Conclusions:Cortisol withdrawal increased insulin sensitivity in terms of increased glucose oxidation and decreased endogenous glucose production; this may induce hypoglycemia in adrenocortical failure. Energy expenditure and urea loss decreased, indicating that weight and muscle loss in Addison's disease is caused by other mechanisms, such as decreased appetite. Increased muscle protein breakdown may amplify the loss of muscle protein.
Restoration of physiological androgen levels using 6 months of DHEA replacement in this pilot study did not affect cardiovascular parameters and endothelial function in female adrenal insufficiency.
Objective: In female adrenal insufficiency, dehydroepiandrosterone (DHEA) secretion is impaired and circulating androgen levels are severely reduced. We wanted to analyse the acute effects of physiological DHEA substitution on substrate metabolism. Design: We studied nine females with adrenal insufficiency after 9 days of oral DHEA replacement (50 mg/day) in a double-blind, placebo-controlled crossover study. Methods: Whole body and regional substrate metabolism was assayed in the basal state and during a euglycemic hyperinsulinemic glucose clamp by means of isotope dilution techniques (glucose, phenylalanine, tyrosine), indirect calorimetry and in situ lipolysis (microdialysis technique). Results: DHEA treatment normalized the levels of all androgens. Basal and insulin-stimulated total energy expenditure and rates of protein, lipid and glucose oxidation were unaffected by DHEA. Whole body turnover of glucose and protein were also unaffected by DHEA. Forearm breakdown of protein was reduced by insulin to the same extent after placebo and DHEA. Insulin sensitivity as expressed by the glucose infusion rate during the euglycemic clamp was similar after placebo and DHEA. Finally, the interstitial release of glycerol in adipose tissue was not significantly influenced by DHEA. Conclusions: Short-term oral DHEA replacement in women with adrenal insufficiency was not associated with measurable changes in total or regional substrate metabolism.European Journal of Endocrinology 152 77-85
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