Endocrine Abstracts

JOINT3762

Jaw Tumor Syndrome (JTS) is a rare, autosomal dominant endocrine syndrome caused by pathogenic variants of the CDC73 gene. The most common manifestation is primary hyperparathyroidism (PHPT), due to adenoma or, more rarely, parathyroid carcinoma. Other manifestations include ossifying fibromas of the jaw, renal cysts and tumors, as well as uterine conditions. However, a concomitant diagnosis of pheochromocytoma has not been identified to date. The clinical case of a 56-year-old woman is presented. She was referred to the Endocrinology department in 2004 due to hypercalcemia and bilateral kidney stones. There were no other significant personal or family medical histories. After investigation, she was diagnosed with primary hyperparathyroidism and underwent a left inferior parathyroidectomy (pathological examination confirmed it was a parathyroid adenoma), along with a left lobectomy and isthmectomy (consistent with nodular thyroid hyperplasia). About two years after the parathyroidectomy, she presented with a progressively worsening expansive lesion of the right upper jaw, causing bone destruction. She underwent surgical intervention, and the diagnosis of a cemento-ossifying fibroma was made. There were no recurrent lesions throughout imaging follow-up. Additionally, the patient had a history of endometrial and endocervical polyps and uterine fibroids (she underwent partial endometrial ablation). In 2008, due to newly developed and difficult-to-control hypertension, further studies were performed, including the measurement of plasma, urinary metanephrines and an abdominal CT scan revealed a 3. 5 cm nodule in the right adrenal gland. She underwent a right adrenalectomy, which confirmed a benign norepinephrine-producing pheochromocytoma. She remained asymptomatic until 2016 when she was hospitalized with a suspected diagnosis of MEN or hereditary pheochromocytoma/paraganglioma. A genetic study was conducted to look for mutations in the SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127 and VHL genes, but no relevant mutations were found. Given her personal history, a diagnosis of JTS was suggested. A subsequent mutational analysis of the CDC73 gene revealed an 8-base deletion in exon 16, resulting in the substitution of lysine with proline at position 474, leading to the appearance of a premature stop codon. Following this result, genetic testing was performed on family members, including her sister(CDC73+ and diagnosed with a 6mm angiomyolipoma in the upper third of the left kidney)and her mother (negative genetic test result). Her father passed away at very young age. Currently, the patient continues to follow up with the Endocrinology consultation, monitoring potential complications related to the syndrome. This case describes the complexity of diagnosing this rare syndrome, which should be considered in the presence of hyperparathyroidism and ossifying jaw tumors. The concomitant presence of pheochromocytoma, not described in the syndrome, made the definitive diagnosis more challenging.