LYSINE VASOPRESSIN STIMULATION OF CORTISOL SECRETION IN PATIENTS WITHADRENOCORTICOTROPIN-INDEPENDENT MACRONODULAR ADRENAL-HYPERPLASIA

We present two patients with Gushing's syndrome due to ACTH-independen t macronodular adrenal hyperplasia who showed marked plasma cortisol r esponse to lysine-8-vasopressin (LVP) injection (from 930 and 731 pmol /L to 2177 and 1920 pmol/L, respectively), while plasma ACTH levels re mained undetectable. The ACTH independence of cortisol secretion in th e two patients was determined from the following endocrinological find ings. Plasma cortisol levels were not increased by corticotropin-relea sing hormone injections and were not suppressed by high dose (16 mg) d examethasone administrations. The plasma ACTH levels, measured by two independent sensitive immunoassays, were persistently undetectable eve n after corticotropin-releasing hormone injection, metyrapone administ ration, and bilateral adrenalectomy. The particular pathological findi ng of the two cases, atrophic lesions in nonnodular parts of the adren al cortexes, also Indicated ACTH independence of the macronodular hype rplasia. In vitro examination revealed a direct effect of LVP on corti sol secretion from the adrenal cells of the macronodules. We also exam ined seven patients with Cushing's syndrome caused by adrenal adenoma and found a statistically significant plasma cortisol response to LVP injection. The direct effect of LVP was also demonstrated in cultured adenoma cells. In conclusion, we discover ed a direct adrenal effect o f LVP on cortisol secretion in patients with ACTH-independent macronod ular hyperplasia and, to a lesser extent, in patients with cortisol-pr oducing adrenal adenoma. The cortisol response to LVP may serve to fac ilitate their diagnosis and choice of therapy.