Integrity of the hypothalamo-pituitary-adrenal axis in morbid human obesity

In unselected groups of obese subjects, a normal response of their hypothalamo-pituitary-adrenal axis (HPAA) to different kinds of stimulation-and suppression-tests has been described. However, in accordance with animal experimentation, recent studies suggest that subtypes of obesity, such as abdominal obesity, may be associated with a lower threshold for stimulation as well as with an impaired suppressibility of the HPAA. The aim of the present study was to investigate whether such alterations in the HPAA may be particularly present in extreme forms of human obesity. Eight morbidly obese patients (141.6+/-31.2 kg; BMI 48.1+/-10.2 kg/m(2); 35.9+/-9.7 years; women/men = 6/2) and eight lean control subjects (66.3+/-5.2 kg; BMI 22.1+/-2.0 kg/m(2); 32.7+/-5.2 years; women/men=5/3) underwent a combined CRH/VP-stimulation test. In addition, a prolonged dexamethasone suppression test was performed in the obese group. There was no difference in the cortisol response after CRH/VP-stimulation between the morbidly obese and the lean control subjects. In addition, cortisol levels were completely suppressed by dexamethasone in all obese subjects without any detectable premature escape. However, the peak ACTH concentration following CRH/VP-stimulation was significantly higher in these patients. The results of this study do not suggest that the HPAA may be particularly altered in extreme degrees of human obesity. Whether the observed augmentation of the ACTH response to CRH/VP stimulation in these patients represents a consistent alteration of the HPAA needs to be clarified in further studies including larger sample sizes.