Lack of Responsiveness to l -Dopa in Cushing's Disease1

l-dopa was administered to 8 patients with Cushing's disease and the resultant response of plasma growth hormone (GH) and cortisol levels was evaluated. Cushing's disease in all patients was secondary to ACTH dependent bilateral adrenal hyperplasia. Four patients had clinically active disease, the four others were in clinical remission. Seven of these subjects failed to demonstrate any elevation in plasma growth hormone levels following l-dopa administration, which is a potent stimulus to growth hormone release in normal subjects. None of the patients showed any change in plasma cortisol levels following administration of l-dopa. These patients also manifested absent growth hormone responsiveness to insulin hypoglycemia, pitressin, and Piromen™ administration. Two of these patients received therapeutic doses of l-dopa for a 5- or 10-week period, in view of reported animal findings postulating a lack of central adrenergic inhibition in Cushing's disease. Neither patient showed any amelioration of the clinical or laboratory parameters of their disease.