Endocrine Abstracts

Introduction: Paragangliomas (PGLs) are rare neuroendocrine tumors that arise from sympathetic or parasympathetic extra-adrenal paraganglia. PGLs have an extremely variable clinical presentation, depending on the localization, tumor size, catecholamine production, compressive symptoms, etc. Germline mutations in PGLs are associated in 30-35% of patients. Mutation in genes encoding the subunits of succinate dehydrogenase (SDH) leads to an increased risk of metastasis, specially SDHB mutation (35-75%). SDHB-related PGLs may be asymptomatic due to low tumoral catecholamine secretion or dopaminergic phenotype.

Case presentation: We report a case of 43-year-old man with no medical history or family history of interest, referred to our department for preoperative study. The patient presented a 4.1×5.2 cm retroperitoneal mass detected on CT scan for pain in the right groin. PGL was the first diagnosis suspicion. Laboratory tests showed 24-hour urinary excretion of normetanephrine, metanephrine and serum chromogranin A concentration within reference range. The patient underwent ¹²³I-MIBG scintigraphy with SPECT/CT that did not detect any functional lesion. Genetic testing was positive for heterozygous mutation in c.565Y>C p.(Cys189Arg) of the SDHB gen (there are 3 familial cases described). Laparotomy resection of the retroperitoneal mass was performed. Postoperative histopathological examination confirmed an extra-adrenal PGL of 4.5 cm. Lymph nodes were negative for malignant cells. During the follow-up, the patient remained well for 4 years (laboratory analysis and control CT were normal). Due to persistent pain in the right groin, laboratory tests and full body scan were carried out before the scheduled date. Surprisingly, significant elevation in 24-h urinary fractionated metanephrines [634μg/24-h (reference range <76 μg/24-h)] and 24-h urinary fractionated normetanephrine [3064 μg/24-h (reference range <444 μg/24-h)] were observed; 3-metoxitiramine and chromogranin were within the normal range. Control CT scan revealed a recurrent retroperitoneal tumor of 3.2×4.7 cm and two new masses (3.3×3.5 cm aortocaval and 1.4×1.9 cm duodenal). SPECT/TC with somatostatin analogue showed pathological accumulation in the described lesions. After alpha blockage with doxazosin, resection of the masses was performed and histopathological examination confirmed to be metastatic PGL. ⁶⁸Ga-DO TATATE PET/CT was carried out in order to consider metabolic therapy, which revealed increased uptake on the residual tumor post operatively.

Conclusions: – The clinical evolution observed in our patient, from non-functional to functional PGL and from localized to metastatic disease, shows us the unpredictable evolution of Cys189Arg mutation of the SDHB gen-related PGL.

– Our case demonstrates the importance of a rigorous follow-up of patients with SDHB-related PGL due to high metastatic potential.