Endocrine Abstracts

Introduction: Paragangliomas belong to the neuroendocrine tumours arising from autonomic nervous system. Various localizations, symptoms that can mimic a wide range of diseases and often unpredictable ability to metastasize are the reasons why paragangliomas pose a significant diagnostic challenge. More than one third of paragangliomas is associated with germline mutations –succinate dehydrogenase (SDH) subunit genes are among the most common susceptibility genes. SDHD was the first among SDH genes identified as being involved in pheochromocytoma/paraganglioma pathogenesis. SDHD mutations are inherited as autosomal dominant trait with a paternal transmission, affected patients usually develop multiple cervical paragangliomas. However, mutations in the SDHD gene do not often predispose to a metastatic evolution.

Case Presentation: We report a case of a 48-year-old woman admitted to the Department of Endocrinology due to suspicion of bilateral cervical paraganglioma – two lesions were visualised on ultrasonography, performed because of concomitant Graves disease. Remarkably, the only sister of the patient died at the age of 47 due to metastatic paraganglioma, 14 years after the diagnosis (SDHD gene mutation was identified), patients’ father was diagnosed with bilateral cervical lesions, died suddenly at the age of 39. Laboratory tests revealed slightly elevated free plasma metanephrine concentration 72,1 pg/ml (reference range <62 pg/ml), free plasma normetanephrine, plasma 3-metoxytyramine and serum chromogranin A concentrations were within reference range. The result of head and neck CT scan confirmed the presence of two carotid lesions: on the right side measuring 21 x 20 x 32 mm, on the left side measuring 13 x 16 x 18 mm (grade I according to the Shamblin classification). Furthermore, the result of thorax CT scan revealed the suspected lesion below the aortic arch, adjoining the aorta, measuring 10 x 15 mm. All three described lesions showed the pathological tracer uptake in somatostatin receptor scintigraphy (99mTc HYNICTOC 720MBq). The molecular analysis revealed pathogenic SDHD gene nonsense variant: c.33C>A (p.(Cys11Ter)). The patient was referred to the Vascular Surgery Department, where two-stages cervical paraganglioma removal was performed. Other family members also underwent the screening for pheochromocytoma/paraganglioma.

Conclusions: Presented case highlights the importance of molecular testing of patients with pheochromocytoma/paraganglioma and the necessity for long-term follow-up. Furthermore, reported case may hint that the clinical course and risk of malignancy is not universal for all SDHD pathogenic mutation carriers, and should be stratified in relation to the carried variant, which may improve the accuracy of genetic counselling, clinical screening, and follow-up strategies.