Endocrine Abstracts

JOINT947

Background: Pheochromocytoma/Paraganglioma (PHEO/PGL) and primary hyperparathyroidism (PHPT) are rare endocrine disorders with distinct etiologies. While PHEO commonly arises from neural crest-derived adrenal chromaffin cells, PHPT typically results from hyperactive parathyroid adenomas. Germline mutations in succinate dehydrogenase (SDH) genes, particularly SDHA, SDHB, SDHC, and SDHD, are implicated in the pathogenesis of PHEO/PGL. SDHA gene mutations are rare and not well characterized, with limited evidence linking them to primary hyperparathyroidism. We present the case of a young woman with concurrent PHEO and PHPT, harboring a novel heterozygous germline SDHA gene mutation.

Case Presentation: A woman in her early 40s presented with recurrent abdominal pain, profound anemia (hemoglobin: 5.6 g/dl), hypercalcemia (ionized calcium: 1.41 mmol/l), and significantly elevated parathyroid hormone (iPTH: 317.5 pg/mL). A large left sided renal mass was identified on an abdominal CT scan. Surgical pathology confirmed a 16.3 cm PHEO, displaying typical zellballen architecture and positive immunohistochemical staining for synaptophysin, chromogranin, and vimentin. Persistent hypercalcemia and elevated iPTH levels led to a neck ultrasound, which revealed a 1.9 x 0.8 x 1.2 cm hypoechoic, hypervascular nodule adjacent to the left thyroid lobe, suggestive of a parathyroid adenoma. Subsequent surgical removal of two hyperplastic parathyroid adenomas normalized serum calcium levels. Genetic testing identified a novel heterozygous germline SDHA gene mutation (p.E640G, c.1919 A>G), classified as a variant of unknown significance (VUS), contributing to the expanding spectrum of SDHA-related disorders. Over a seven-year follow-up period, the patient demonstrated an indolent clinical course, with no evidence of metastasis despite the large size of the initial PHEO. Serial PET-CT imaging (F-FDG and Ga-DOTATATE) and normal plasma metanephrines consistently showed no signs of disease progression. To date, the coexistence of PHEO and PHPT associated with SDHA gene mutations has not been previously documented. Additionally, the indolent course during an extended follow-up period is particularly significant, as it contrasts with the typically aggressive course often observed in SDHA-related PHEO/PGL.

Conclusion: This unique case highlights the importance of genetic testing in atypical presentations of endocrine neoplasms to understand risk of disease progression and guide surveillance. Further research is warranted to clarify the role of novel SDHA gene variants in coexisting endocrine disorders.