Little is known about the effects of intentional
weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2) before and after a 21.0 +/- 7.9-kg
weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before
caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated
ACTH and
cortisol values were compared to those of a control group of 12 normal weight women. Before
caloric restriction, both
ACTH and
cortisol responses to oCRH were similar in obese women and normal weight controls.
Weight loss did not significantly alter the
ACTH response to oCRH; however, the total plasma
cortisol response to oCRH decreased significantly with
weight loss (area under the curve, 96,320 +/- 21,040 nmol/L x min before
weight loss; 82,450 +/- 22,460 nmol/L x min after
weight loss; P < 0.001).
Cortisol-binding globulin also decreased significantly after
weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before
weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free
cortisol, either before or 180 min after oCRH treatment, showed no significant changes in
cortisol responses resulting from
weight loss. As plasma free
cortisol was not altered by
weight reduction, the decrease in the total
cortisol response to oCRH after
weight loss appears to be secondary to significant decreases in
cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such
weight reduction does not significantly affect the HPA axis.