IL-6-Producing Pheochromocytoma Associated With Von Hippel Lindau Disease: A Case Report With Literature Review

We present a first case report of an IL -6 -producing pheochromocytoma associated with von Hippel Lindau (vHL) disease. Pheochromocytomas are rare tumors that produce catecholamines, leading to various symptoms. In this case, a 28 -year -old woman with a family history of vHL disease presented with a prolonged fever. Laboratory examinations revealed elevated C -reactive protein levels, and notably, a significantly increased serum IL -6 level. Imaging studies confirmed bilateral adrenal tumors with increased uptake on fluorodeoxyglucose-positron emission tomography and 123I-metaiodobenzylguanidine scintigraphy in the right adrenal gland. Despite partial relief with nonsteroidal anti-inflammatory drugs and alpha-blockers, her fever persisted until prednisolone administration, which promoted a complete resolution. A histopathological analysis following a right laparoscopic adrenalectomy revealed a typical pheochromocytoma. We conducted further analyses, including an enzyme -linked immunosorbent assay (ELISA), a quantitative real-time polymerase chain reaction (PCR) test, and immunoblot assays from the resected tumor tissues. We compared the current case with other cases of pheochromocytoma that presented neither elevated serum IL -6 nor high fever. Using ELISA, we found that this patient exhibited more IL -6 secretion than that seen in other cases. Additionally, quantitative real-time PCR and immunoblot found that both the phosphorylated signal transducer and activator of transcription 3 (STAT3) messenger RNA (mRNA) and protein expression levels exceeded those of the other cases. Thus, we surmised that IL -6 was produced directly from the tumor tissue and IL -6 expression was potentiated through the IL-6/STAT3 signaling pathway. Our findings contribute to the understanding of IL -6 -producing pheochromocytomas and their distinct clinical characteristics.