Cyproheptadine may act at the pituitary in Cushing's disease: evidence from CRF stimulation

Cyproheptadine has been reported to effect remissions in up to 50% of patients with Cushing's disease presumably at a hypothalamic level. Endocrine studies including CRF testing were performed in a 37-year-old woman with Cushing's disease. Cyproheptadine therapy resulted in a clinical and chemical remission. During therapy, basal plasma and urinary steroid levels were normal as were responses to dexamethasone, metyrapone, and insulin induced hypoglycemia. CRF administration in the untreated patient resulted in a markedly exaggerated increase in plasma ACTH and cortisol levels, while with cyproheptadine therapy responses were considerably blunted but still greater than normal. These observations are the first to provide evidence supporting a pituitary effect of cyproheptadine in Cushing's disease in vivo and raise questions regarding the assumption of hypothalamic dysfunction in those patients with Cushing's disease responding to cyproheptadine.