SUN-721 The 20-Year Comeback: Revisiting HPT-JT with a Novel Genetic Mutation

Abstract Disclosure: K. Bashir: None. P. Behary: None. M. Siddiqui: None. A. Comninos: None. J. Cox: None. Management of recurrent primary hyperparathyroidism (PHPT) poses a significant challenge in patients with Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), a rare autosomal dominant disorder linked to CDC73 mutations. While most cases of HPT-JT present with single-gland involvement at the initial surgery, metachronous multiglandular disease can lead to recurrence following selective parathyroidectomy in up to 17.6% of cases, with a mean disease-free interval of 13.7 years (range: 5-27 years). This case report details the clinical journey of a 57-year-old woman diagnosed with HPT-JT due to a novel heterozygous CDC73 missense variant (Chr1: g.193091353T>G, c.23T>G, p.(Leu8Arg)). This variant has not been identified in the gnomAD database (∼125,000 individuals) and may therefore represent a de novo mutation. Her medical history includes a hysterectomy in her 40s for fibroids, a history of renal calculi, and a cemento-fibro-osseous jaw lesion identified on orthopantomogram. She initially underwent bilateral neck exploration with the removal of two parathyroid glands in 1997 at the age of 30, achieving a disease-free interval of over 20 years.However, by late 2020, biochemical evidence of recurrent PHPT (adjusted calcium: 2.70 mmol/L [reference range: 2.2-2.6], PTH: 21.2 pmol/L [reference range: 2.2-14]) emerged. Given her increased cardiovascular risk due to coexisting type 2 diabetes, hypertension, and a history of nephrolithiasis, repeat parathyroidectomy was recommended following a multidisciplinary team (MDT) discussion. Imaging, including ultrasound, Sestamibi, and 4D-CT, demonstrated concordance in localizing a left superior parathyroid adenoma, which was successfully excised. Postoperative biochemistry confirmed normalization of calcium and PTH levels, and histopathology confirmed a parathyroid adenoma. Her family history revealed that her 37-year-old daughter had undergone parathyroidectomy at the age of 24 for PHPT, subsequently developing hypoparathyroidism. Genetic testing of both mother and daughter confirmed the novel CDC73 mutation, prompting ongoing family segregation analysis. This case underscores the need for lifelong surveillance in CDC73 mutation carriers due to the persistent risk of PHPT recurrence. It highlights the hereditary nature of HPT-JT and the crucial role of advanced imaging in surgical planning. Successful reoperation demonstrates that, despite the complexity of recurrent PHPT, precise preoperative localization and surgery in a high-volume centre can achieve excellent outcomes. The identification of this novel CDC73 mutation broadens the genetic landscape of HPT-JT, raising key questions about its pathogenicity. Given the rarity of such variants, further research is essential to refine management strategies. Comprehensive family screening remains vital for early detection and intervention. Presentation: Sunday, July 13, 2025