Corticotropin Releasing Hormone Administration Increases Alpha-Melanocyte-Stimulating Hormone Levels in the Inferior Petrosal Sinuses in a Subset of Patients with Cushing’s Disease

Abstract

The effect of corticotropin (ACTΗ-releasing hormone (CRH) administration on α-melanocyte-stimulating hormone (α-MSH), ACTH and β-endorphin (β-EPH) was evaluated in the inferior petrosal sinuses and in the periphery of 30 patients affected with Cushing’s disease subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Baseline PRL levels, sensitivity to dexamethasone and surgery outcome were compared to α-MSH response. CRH bolus did not modify α-MSH concentrations either in the inferior petrosal sinuses or in the periphery in the 30 patients considered as a whole. In 7 of 30 patients, however, a greater than 50% increase over baseline α-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 ± 4.6ng/l; p < 0.001), whereas no change was found in the contralateral inferior petrosal sinus or in the periphery. Conversely, as expected, ACTH and β-ELI significantly increased in all the patients after CRH both in the inferior petrosal sinuses and in the periphery (particularly in the inferior petrosal sinus ipsilateral to the adenoma). No difference in sensitivity to dexamethasone (urinary cortisol percent decrease: 66.4 ± 4.9 vs. 67.8 ± 3.4) and surgery outcome (χ² test: p = 0.7) was found between patients with α-MSH response to CRH and patients without such a response. By contrast, baseline PRL levels, although being normal in both groups, were significantly higher in patients with α-MSH response to CRH (18.1 ± 1.6 vs. 10.1 ± 0.7 μg/l; p < 0.001). In conclusion, the results of the present study suggest that in a subset of patients with Cushing’s disease (23.3% of our series) α-MSH may be released after the administration of CRH together with ACTH and β-EPH by adenomatous corticotrophs. In this subset of patients, PRL levels may be in the upper normal range.

Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin‐releasing hormone and comparison with patients without Cushing's disease

“…Tests were performed as above. The IPSS was performed by the percutaneous femoral approach as already reported (Lombardi et al, 1987;Merola et al, 1992;Colao et al, 1992;1993a,b;1996). Central venous samples (10-15 ml) were taken simultaneously from both inferior petrosal sinuses before performing venograms and 3-5 min after the catheter had reached the sinuses.…”