Endocrine Abstracts

Introduction: Hyperparathyroidism-Jaw Tumour syndrome is a rare autosomal dominant disorder involving parathyroid tumors, ossifying jaw fibromas, renal abnormalities, and uterine hyperplasia or neoplasia. This condition is linked to inactivating mutations in the CDC73 gene, which encodes Parafibromin, a protein with anti-proliferative functions. Patients often present with hyperparathyroidism symptoms like hypercalcemia, as well as jaw tumors.

Case History: A 38-year-old man was referred to his GP for depression. Routine blood tests showed hypercalcemia (corrected Ca 3.21 mmol/l), high parathyroid hormone (PTH) at 38.1 pmol/l, low phosphate (0.62 mmol/l), and low vitamin D (26.2 nmol/l). He had a history of parathyroidectomy age 13, of a 2 cm left parathyroid adenoma. Genetic testing at that time ruled out MEN1, His father had undergone parathyroidectomy at 27 for nodular hyperplasia. The patient was admitted, treated with IV fluids and cinacalcet. Ultrasound showed a 14x12x16mm hypoechoic nodule by the right thyroid gland, later confirmed on Parathyroid MIBI. Post-parathyroidectomy, PTH and calcium levels normalized. Histology confirmed an adenoma and residual scar tissue. Genetic testing diagnosed HPT-JT syndrome.

Discussion: In familial primary hyperparathyroidism (PHPT), it is essential to recognize the genetic variants implicated in its pathogenesis, including those in the CDC73, CDKN1B, GCM2, MEN1, RET, and CASR genes. Current guidelines recommend genetic testing for familial PHPT in individuals under 50, those with significant family history, or cases involving parathyroid carcinoma. Overlapping indications for testing include neonatal hyperparathyroidism and features of multiple endocrine neoplasia, emphasizing the need for a thorough evaluation in suspected cases. This case identified the need to retest those with likely familial PHPT diagnosis despite previously negative genetics given the evolution of genetic testing. This enables appropriate holistic follow-up to be established.