Leuprolide acetate therapy in LH-dependent Cushing's syndrome: in vivo and in vitro observations.

In Cushing’s syndrome, there is an excess of cortisol secretion due to hyperfunction of the adrenal cortex. Hypersecretion of cortisol may be ACTH dependent or independent. The latter is present in an adrenal adenoma/carcinoma or bilateral macronodular adrenal hyperplasia. In some of these patients cortisol secretion is driven by stimuli other than ACTH, such as gastric inhibitory polypeptide (GIP), vasopressin, catecholamines or luteinising hormone (LH). LH-responsive Cushing’s syndrome was first described by Lacroix et al. In their patient in vivo investigations demonstrated that cortisol secretion was LH driven, but in vitro investigations were not performed. Recently, in vitro studies in two patients with LH-responsive Cushing’s syndrome demonstrated LH receptor mRNA in hyperplastic adrenal cells. Definitive proof that cortisol secretion was LH dependent could not be provided, because both patients refused LH-suppressive therapy. We now report another patient with LH-responsive Cushing’s syndrome. Our patient responded to GnRH agonist therapy with a profound decrease in 24-hour urinary cortisol excretion, which proves that in this patient cortisol secretion was indeed LH driven. In vitro studies demonstrated LH receptor mRNA expression in the adrenal cells.