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This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/E848    most recent 00254.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Kok, P. Articles by Pijl, H. Search for Related Content PubMed PubMed Citation Articles by Kok, P. Articles by Pijl, H.

Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment

Departments of ¹General Internal Medicine, ²Radiology, ³Endocrinology and Metabolic Diseases, ⁴Clinical Chemistry, and ⁵Nuclear Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Submitted 14 June 2004 ; accepted in final form 20 July 2004

Several studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 ± 0.9 vs. lean 21.2 ± 0.6 kg/m², P < 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 ± 1,212 vs. 2,808 ± 329 ng/24 h, P = 0.002), whereas cortisol was not altered (obese 36,362 ± 5,639 vs. lean 37,187 ± 4,239 nmol/24 h, P = 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 ± 769 ng/24 h, P = 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 ± 3,436 nmol/24 h, P = 0.484 vs. placebo). In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly.

adrenocorticotropic hormone; spontaneous secretion; pituitary adrenal system; free fatty acids; obesity