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Abnormalities of the Hypothalamic-Pituitary-Adrenal Axis in Nondepressed Women with Abdominal Obesity and Relations with Insulin Resistance: Evidence for a Central and a Peripheral Alteration

Endocrinology Unit, Department of Internal Medicine and Gastroenterology, St. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy

Address all correspondence and requests for reprints to: Prof. Renato Pasquali, Unita di Endocrinologia, Dipartimento di Medicina Interna and Gastroenterologia, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. E-mail: rpasqual{at}almadns.unibo.it

We have previously shown that women with abdominal body fat distribution (A-BFD) have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis. However, we did not consider the presence of anxiety and/or depression, common manifestations in obese subjects. Anxiety and depression may be associated with oversecretion of cortisol and could represent a confounding factor in the evaluation of the HPA axis in different obesity phenotypes. In this study nondepressed obese women with abdominal and peripheral (P-BFD) body fat distribution and a control lean group underwent a CRH/AVP stimulation test for ACTH and cortisol determinations. Moreover, all women underwent metabolic evaluation and had their urinary free cortisol (UFC) excretion measured. After the stimuli, ACTH and cortisol responded more in the A-BFD than in the P-BFD and control groups. A positive correlation was found between either ACTH area under the curve (r² = 0.366; P = 0.003) or cortisol area under the curve (r² = 0.378; P = 0.043) and the homeostasis insulin resistance index in all obese patients. Unexpectedly, A-BFD had significantly lower UFC per m² values than P-BFD (P < 0.05). Lowered UFC excretion in the A-BFD group is in keeping with an increased cortisol clearance, which, in turn, may lead to HPA axis hyperactivity as an appropriate compensatory mechanism. On the other hand, other mechanisms, possibly central in origin, such as overdriving of the CRH-ACTH system to chronic environmental stress factors, may be involved in determining HPA overresponsiveness in abdominal obesity. In conclusion, this study suggests that women with the abdominal obesity phenotype are characterized by both central and peripheral alterations of the HPA axis activity.

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