Open AccessA Multifocal Paraganglioma in an African Male Due to an Underlying SDHB Mutation
Author(s) -
Nida Siddiqui,
Faheem Seedat,
Saajidah Bulbulia,
Amanda Krause,
Reyna Daya,
Zaheer Bayat
Publication year - 2021
Publication title -
journal of the endocrine society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.046
H-Index - 20
ISSN - 2472-1972
DOI - 10.1210/jendso/bvab048.209
Subject(s) - sdhb , normetanephrine , medicine , metanephrine , pheochromocytoma , paraganglioma , palpitations , germline mutation , headaches , metanephrines , blood pressure , endocrinology , radiology , surgery , mutation , biology , biochemistry , gene
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from adrenal and extra-adrenal paraganglia. Up to forty percent are due to an underlying germline mutation. Mutations in the subunit B gene of the SDH complex (SDHB) are associated with PGL syndrome four. A 34-yr-old African man from Southern Africa presented with a two-year history of sustained hypertension associated with the classic triad of sweating, headaches and palpitations. Family history was contributory towards early unexpected deaths of his father (age 42) and two younger brothers (ages 13 and 14 respectively). On examination his blood pressure was persistently elevated measuring 146/87mmHg. In view of the classic presenting symptoms and hypertension onset at a young age, a PPGL was suspected. Biochemical investigations were positive with an elevated 24-hour urine normetanephrine level of 35807 (480-2424nmol/24hours), normal metanephrine level of 689 (264-1729nmol/24hours), an elevated normetanephrine:creatinine ratio of 3270 (28-158nmol/mmol creatinine) and an elevated methoxytyramine level 4941.69nmol/24 hours (<800nmol/24 hours). Computed tomography of the abdomen and neck revealed a homogenous soft tissue mass measuring 5.9cm x 3.6cm x 6.6cm anterior to the right kidney and separate from the right adrenal gland and a carotid body tumor measuring 3.6cm x 2.9cm x 4.1cm. Both were radio-avid on a [68Gallium]-DOTATATE-Positron Emission Tomography (PET)-CT. There were no features to suggest metastatic disease. Genetic testing is not available in South Africa; therefore, testing was done at an international laboratory. This revealed a pathological SDHB mutation variant, c.724C>A p.(Arg242Ser) and hence PGL4 syndrome. The patient underwent staged surgery with successful removal of the intra-abdominal tumor. Unfortunately, due to peri-operative complications associated with the second surgery, the patient demised. Histopathological examination of both tumors was consistent with a paraganglioma. Genetic counselling and testing were offered to all living first-degree relatives. His sister tested positive for the same pathological variant. His 6-week-old son will be offered counselling and testing at a later stage. To the best of our knowledge, we are the first to describe the missense SDHB mutation (pathogenic variant c.724C>A p.[Arg242Ser]) and the occurrence of an SDHB associated PGL in a family of African ethnicity. This case highlights the importance of genetic counselling and testing in patients with a confirmed PPGL. Due to resource limitation the African population remains under represented in genetic studies which limits the utility of precision medicine in this group. As such, our case is an important addition to the body of knowledge in this growing field and highlights the need for cost effective genetic screening tools in low resourced settings.