Alpha-Melanocyte-Stimulating Hormone Is Present in the Inferior Petrosal Sinuses in Patients with Cushing’s Disease

Abstract

Plasma ACTH, β-endorphin and α-melanocyte-stimulating hormone levels were evaluated in the inferior petrosal sinuses and in the periphery of 22 patients affected by Cushing’s disease, 11 patients with other pituitary diseases subjected to simultaneous and bilateral inferior petrosal sinus sampling and in the peripheral blood of 15 normal subjects. In patients with Cushing’s disease ACTH, β-endorphin and α-melanocyte-stimulating hormone levels in the inferior petrosal sinus ipsilateral to the adenoma were significantly higher than in the periphery and in the contralateral inferior petrosal sinus (p < 0.01, p < 0.01 and p < 0.05, respectively). In patients with other pituitary diseases only ACTH and β-endorphin, but not α-melanocyte-stimulating hormone levels in both inferior petrosal sinuses were significantly higher than in the periphery (p < 0.01). Furthermore, no difference was found in the peripheral blood among patients with Cushing’s disease, patients with other pituitary diseases and normal subjects for ACTH and β-endorphin level. By contrast, in patients with Cushing’s disease peripheral α-melanocyte-stimulating hormone levels were significantly higher than in patients with other pituitary diseases and in normal subjects (p < 0.05). In conclusion, the results of the present study suggest that only in patients with Cushing’s disease, but not in patients with other pituitary diseases, α-melanocyte-stimulating hormone is released by adenomatous pituitary corticotrophs together with ACTH and β-endorphin.

Inferior petrosal sinus ACTH and prolactin responses to CRH in ACTH-dependent Cushing’s syndrome: a single centre experience from the United Kingdom

“…It has long been recognised that in addition to ACTH, intersinus gradients for prolactin, growth hormone, thyrotrophin-secreting hormone, alpha-human chorionic gonadotrophin and beta-endorphin [14][15][16][17][18] can be detected in blood samples from inferior petrosal sinuses of patients with surgically and histologically confirmed Cushing's disease in the basal unstimulated state. Moreover, stimulation with CRH has been shown to induce further increases in the concentrations of prolactin, growth hormone, thyroid-stimulating hormone, alpha-subunit, tumour necrosis factor-alpha, alpha-melanocyte stimulating hormone and arginine vasopressin [14,[19][20][21][22][23][24][25][26] in blood from the dominant inferior petrosal sinus (the petrosal sinus with the maximal ACTH response), although these paradoxical responses of other hormones are not consistently seen [27]. It is also possible that corticotroph cells are capable of secreting prolactin but not able to store this hormone or that CRH used for stimulation during IPSS is contaminated with peptide fragments that can release pituitary hormones other than ACTH.…”

Tumor Necrosis Factor-Alpha Increases after Corticotropin-Releasing Hormone Administration in Cushing’s Disease

“…Before CRH bolus, samples for plasma ACTH, (3-EPH and serum TNFa assay were collected twice at 5-min intervals and the average value was considered. SBIPSS was obtained by the percuta neous femoral approach, as reported elsewhere [6][7][8][9][10][11][12], between 09.00 and 11.00 a.m. Peripheral venous samples were obtained simultaneously by a catheter needle previously inserted in an antecubital vein and kept patent by slow saline infusion.…”

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

“…Conversely, corticotrophs secrete preferentially ACTH, fi-lipotropin and P-EPH [1,7], although it has been shown that a subset of these cells contains a-MSH [8], Some of the peptides produced by mclanotrophs (a-MSH and CLIP), however, have been identified in adult human pituitary tissue despite the fact that the adult human pituitary lacks a dis tinct pars intermedia [9], Moreover, the regulation of POMC-derived peptides is different in corticotrophs and mclanotrophs, the former being regulated mainly by CRH and vasopressin [10][11][12] and the latter by direct neural connections, inhibitory (dopamine and y-amino butyric acid) and stimulatory (serotonin) [13][14][15], On this basis it was suggested that the presence of hyperprolactinemia, the response to dopamine agonists, the poor sensitivity to dexamethasonc and surgery outcome may distinguish be tween anterior pituitary and intermediate lobe corticotroph tumors [4], Pathophysiology of a-MSH secretion in humans is still unclear. In fact, data reported in literature on a-MSH con centrations in the peripheral plasma arc quite controver sial [16][17][18], In a previous study [ 19] we demonstrated the presence of a significant a-MSH concentration gradient between the inferior petrosal sinus ipsilateral to the pitu itary adenoma and the periphery in patients with Cush ing's disease but not in patients with acromegaly or hyper prolactinemia. Therefore, we suggested that in baseline conditions a-MSH release does exist, at least in Cushing's disease.…”

“…during the simultaneous and bilateral inferior petrosal sinus sampling. This technique has been widely shown as a very useful test to differentiate between ectopic and pituitary ACTH-dependent Cush ing's syndrome [27][28][29][30][31][32][33][34] and may offer the possibility to study the secretory pattern of pituitary hormones [ 19,23,[35][36][37][38][39], In fact, by this technique we were able to show a significant (greater than 50%) a-MSH release after CRH administration in a subset of patients with Cushing's dis ease (23.3%), only when blood samples were collected in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma but not in the contralateral one or in the peripheral blood. Therefore, we could speculate that a-MSH may be released together with ACTH and [3-ELI in certain patients with Cushing's disease, although in amounts too small to be detectable in the peripheral plas ma.…”