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

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Abstract
The aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 µg, as i.v. bolus) on tumor necrosis factor-α (TNFα) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing’s disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, β-endorphin (β-EPH) and TNFα were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNFα concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 µmol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and β-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNFα levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), β-EPH (p < 0.01) and TNFα (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, β-EPH and TNFα levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 µmol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNFα concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNFα release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNFα production can be detected in ACTH-secreting adenomas.

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