Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma

It has been demonstrated that adrenomedullin, a newly discovered peptide wi th structural similarity to calcitonin gene-related peptide (CGRP), is expr essed in pituitary gland and affects basal and corticotropin (ACTH)-releasi ng factor (CRF)-stimulated ACTH release in animals, thus suggesting its pot ential role in regulating the hypothalamus-pituitary-adrenal axis. To evalu ate whether ACTH and cortisol levels affect adrenomedullin production in hu mans, we studied 14 patients with Gushing's syndrome due to pituitary adeno ma and 8 patients with Gushing's syndrome due to adrenal tumor, with measur ement of circulating adrenomedullin by a specific radioimmunoassay (RIA). A drenomedullin concentrations were significantly higher in patients with pit uitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) a nd patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surg ical treatment, plasma adrenomedullin decreased significantly. In one patie nt with Gushing's syndrome due to pituitary adenoma who underwent simultane ous sampling of the inferior petrosal venous sinuses, the adrenomedullin co ncentration was significantly higher in plasma collected from the side with the adenoma and increased after GRF administration (Delta increase, 42.6%) , according to ACTH levels. Our findings indicate that circulating adrenome dullin is increased in Gushing's disease, and the pituitary gland may repre sent the site of the elevated production of adrenomedullin in this conditio n. Copyright (C) 2000 by W.B. Saunders Company.