MON-249 SDHD Mutation: Nonfunctional Paragangliomas Presenting as Bilateral Carotid Body Tumors with Syncope

SDHD Mutation: Nonfunctional paragangliomas presenting as bilateral carotid body tumors with syncope Background: A mutation of the SDHD gene is associated with hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes which most commonly originate in the head and neck region, and usually form in the carotid body. Paragangliomas (PGL) can be secretory or non-secretory with about 95% of head and neck PGL being non-secretory. They can rarely present with symptoms due to compression, however, as in this case of a 29 year-old female presenting with syncope. Clinical Case: A 29 year-old female presented for evaluation after syncope. She had a syncopal event and fell down while walking in her home. Syncope was preceded by about 15 minutes of flushing, nausea and palpitations. She reported similar episodes once weekly in the preceding months, which generally lasted an hour. Initial workup included normal vital signs at presentation, normal ECG and echocardiogram, normal TFT, CBC, complete metabolic panel. Subsequent head/neck CT revealed bilateral masses in the carotid bifurcations consistent with carotid body tumors. Further history revealed a family history of bilateral carotid body tumors in her father which had never been evaluated. Plasma and urine metanephrines were normal. She underwent carotid body tumor excision. The left carotid body tumor was successfully excised and pathology revealed a paraganglioma with positive synaptophysin and chromogranin stains. Genetic testing revealed an SDHD (succinate dehydrogenase complex subunit D) gene mutation. Repeat biochemical assessment 4 months later was again negative and patient remained asymptomatic postoperatively. Conclusion: Paragangliomas can be secretory or non-secretory with about 95% of head and neck paragangliomas being non-secretory, as in this case. Symptoms can arise from catecholamine hypersecretion, which generally presents as hypertension, headaches, diaphoresis, flushing, anxiety or palpitations, and can be episodic or sustained, or mass effect. Syncope as a presenting symptom is rare, however, and has not been quantified but only reported in case reports. The exact etiology of syncope in our patient is not clear. Hereditary PGL/PCC syndromes should be suspected in any individual with multiple, recurrent, early-onset (age less than 45 years) or family history of PGL/PCC, as these syndromes are inherited in an autosomal dominant manner.

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early.

Risk of metastatic pheochromocytoma and paraganglioma in SDHx mutation carriers: a systematic review and updated meta-analysis

BackgroundPheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.MethodsWe searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.ResultsThe highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%–41%) and the lowest risk by SDHD mutation (~4%).ConclusionThere was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.