TUMOR-NECROSIS-FACTOR-ALPHA INCREASES AFTER CORTICOTROPIN-RELEASING HORMONE ADMINISTRATION IN CUSHINGS-DISEASE - IN-VIVO AND IN-VITRO STUDIES

The aim of this study was to evaluate the effect of acute human cortic otropin (ACTH)-releasing hormone (CRH) administration (100 mu g, as i. v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inf erior petrosal sinuses and in the peripheral blood of 7 patients with Gushing's disease subjected to diagnostic inferior petrosal sinus samp ling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneo usly. In addition, TNF alpha concentrations were measured after CRH ad ministration (10 nmol/l, 100 nmol/l and 1 mu mol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior pe trosal sinus ipsilateral to the ACTH-secreting adenoma than in the con tralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ip silateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alph a levels in the culture medium of three ACTH-secreting tumors at the d oses of 100 nmol/l and 1 mu mol/l (greater than 300, 200 and 110% of b aseline pretreatment incubation levels, respectively). These data sugg est that CRH may increase TNF alpha concentrations in the inferior pet rosal sinus ipsilateral to the ACTH-secreting adenoma and in the perip heral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH -secreting adenomas.