CORTICOTROPIN-RELEASING HORMONE ADMINISTRATION INCREASES ALPHA-MELANOCYTE-STIMULATING HORMONE LEVELS IN THE INFERIOR PETROSAL SINUSES IN A SUBSET OF PATIENTS WITH CUSHINGS-DISEASE

The effect of corticotropin (ACTH)-releasing hormone(CRH) administrati on on alpha-melanocyte-stimulating hormone (alpha-MSH), ACTH and beta- endorphin (beta-EPH) was evaluated in the inferior petrosal sinuses an d in the periphery of 30 patients affected with Gushing's disease subj ected to simultaneous and bilateral inferior petrosal sinus sampling f or diagnostic purposes. Baseline PRL levels, sensitivity to dexamethas one and surgery outcome were compared to alpha-MSH response, CRH bolus did not modify alpha-MSH concentrations either in the inferior petros al sinuses or in the periphery in the 30 patients considered as a whol e. In 7 of 30 patients, however, a greater than 50% increase over base line alpha-MSH levels (from 50 to 115.5%) was recorded in the inferior petrosal sinus ipsilateral to the adenoma (from 42.9+/-1.7 to 76.4+/- 4.6 ng/l; p <0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and beta-ELI significantly increased in all the patients after CR H both in the inferior petrosal sinuses and in the periphery (particul arly in the inferior petrosal sinus ipsilateral to the adenoma). No di fference in sensitivity to dexamethasone (urinary cortisol percent dec rease: 66.4+/-4.9 vs, 67.8+/-3.4) and surgery outcome (chi(2) test:p=0 .7) was found between patients with alpha-MSH response to CRH and pati ents without such a response. By contrast, baseline PRL levels, althou gh being normal in both groups, were significantly higher in patients with alpha-MSH response to CRH(18.1+/-1.6 vs. 10.1+/-0.7 mu g/l p <0.0 01). In conclusion, the results of the present study suggest that in a subset of patients with Gushing's disease (23.3% of our series) alpha -MSH may be released after the administration of CRH together with ACT H and beta-EPH by adenomatous corticotrophs. In this subset of patient s, PRL levels may be in the upper normal range.