Food-dependent Gushing's syndrome: Possible involvement of leptin in cortisol hypersecretion

Stimulation of cortisol secretion by food intake has been implicated in the pathogenesis of some cases of ACTH-independent Gushing's syndrome, via an aberrant response of the adrenal glands to gastric inhibitory polypeptide ( GIP). We report here a novel case of food-dependent Gushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia. In this patient w e were able to confirm a paradoxical stimulation of cortisol secretion by G IP in vivo as well as in vitro on dispersed tumor adrenal cells obtained at surgery. In addition to GIP, in vitro stimulation of these cultured tumor adrenal cells with leptin, the secreted product of the adipocyte, induced c ortisol secretion. By comparison, no such stimulation was observed in vitro in adrenal cells obtained from another patient with bilateral macronodular adrenal hyperplasia and Gushing's syndrome that did not depend on food int ake, in tumor cells obtained from a solitary cortisol-secreting adrenal ade noma, and in normal human adrenocortical cells. These results demonstrate that as in previously described cases of food-dep endent Gushing's syndrome, GIP stimulated cortisol secretion from the adren als of the patient reported here. Therefore, they indicate that such a para doxical response probably represents the hallmark; of this rare condition. In addition, they suggest that leptin, which normally inhibits stimulated c ortisol secretion in humans, participated in cortisol hypersecretion in thi s case. Further studies in other cases of food-dependent Gushing's syndrome , however, will be necessary to better ascertain the pathophysiological sig nificance of this finding.