SAT-334 A Genetic Cause of Primary Hyperparathyroidism

Abstract

Background: Primary hyperparathyroidism is a relatively common endocrine condition, affecting up to 7 out of every 1000 adults. Median age of onset is during the sixth decade of life. When present in younger patients primary hyperparathyroidism may indicate an underlying genetic cause. Case: A 23-year-old woman is referred for evaluation of hypercalcemia that was found on labs drawn after surgery for bilateral ovarian cyst removal. At the time of presentation she felt well and was without complaint. Her medical history is otherwise unremarkable. Her family history includes multiple family members with nephrolithiasis. Physical exam revealed a well appearing Caucasian woman without a palpable neck mass. Laboratory results showed: serum calcium 11.7 mg/dL (ref 8.4–10.2), ionized calcium 1.44 mmol/L (ref 1.12–1.32) and serum PTH 192 pg/mL (ref 11–65). Technetium-99 sestamibi scan revealed a low attenuating mass with focal and persistent uptake just inferior to the left thyroid lobe. She subsequently underwent left inferior parathyroidectomy, which confirmed parathyroid adenoma, with resultant normalization of serum calcium and PTH. Due to her young age of diagnosis genetic testing was performed which revealed a mutation if CDC 73. Discussion: CDC 73 mutation is known cause of inheritable neoplasia’s with a high prevalence of parathyroid dysfunction. Although penetrance and expression is variable, the mutation is associated primarily with Hyperparathyroidism Jaw Tumor Syndrome (HPT-JT), Familial Isolated Hyperparathyroidism and sporadic parathyroid carcinoma. Our patient had an allele mutation associated with HPT-JT. This syndrome classically presents with parathyroid adenoma, ossifying tumors of the mandible and renal or uterine neoplasms. The mutation is inherited in an autosomal dominant pattern and family history plays a key role in diagnosis of this rare condition. This patient had an early age of onset for hyperparathyroidism and a family history suggestive of an inherited calcium metabolism disorder. A single parathyroid adenoma is the most common presentation and surgical resection is often curative of hyperparathyroidism. In Hyperparathyroidism Jaw Tumor Syndrome patients classically develop ossifying tumors of the mandible and renal or uterine neoplasms in addition to parathyroid lesions. Rarely patients with CDC 73 mutation can develop parathyroid carcinoma. For this reason it is recommended that all first degree relatives undergo testing for CDC 73 mutation. This patient currently has no evidence of jaw, uterine or renal tumors on screening imaging. Ovarian tumors have been described separately to be associated with CDC 73 mutation, this patient may actually have an unrecognized phenotype of CDC 73 mutation. Given the potential impact of inheritable neoplasia, all young patients with unexplained hyperparathyroidism should be considered for genetic screening.