SAT-353 Familial Hyperparathyroidism - Due to a Rare Genetic Mutation

Abstract

Introduction: Hyperparathyroidism occurs most commonly in middle age patients, predominantly in women. It can be caused by parathyroid adenoma, hyperplasia or parathyroid carcinoma. Genetic predisposition can be found in about 10% of primary hyperparathyroidism due to certain gene mutations. This case emphasizes the importance of taking a detailed family history when patients present with hyperparathyroidism at a young age, so that familial hyperparathyroidism, if present, can be detected and relatives screened.Clinical case: A 26 y.o. male presented with symptoms of fatigue and polydipsia for several years.He was noted to have a serum calcium of 12.4 mg/dL(8.5–10.5), with parathyroid hormone of213 pg/ml (15–65). He denied any history of kidney stones, fractures and no palpable neck masses. The patient’s family history was significant for his paternal half-sister who had parathyroidectomy for hyperparathyroidism at 20yrs old and paternal grandmother died of parathyroid cancer in her 50s. The patient’s father died of pancreatic cancer at 41yrs old. A neck ultrasound revealed a mass posterior to the left inferior thyroid. A Sestamibi parathyroid scan revealed a parathyroid adenoma at the posteroinferior aspect of the left hemithyroid. Labs for free metanephrines and normetanephrine, prolactin and gastrin levels were all normal.Due to his young age and the possibility of having familial hyperparathyroidism, he underwent bilateral neck exploration and parathyroidectomy, with removal of his left inferior, right superior, left superior parathyroid glands and left upper thymus. Surgical pathology revealed, hypercellular parathyroid tissue. Post operatively, his calcium and vitamin D remained within the normal range.Genetic studies revealed a mutation in the parafibromin gene - CDC73 (also called HRPT2), a tumor suppressor gene, which is on chromosome 1q25. The patient currently has 6 children ranging from age 5 months to 6 years. He was advised to have his children tested any time from age 7 years for the gene mutation.The patient has remained stable 4yrs post operatively, with normal calcium and PTH levels. He does not have any history of jaw tumor. He never had an ultrasound kidney done. He is being monitored with yearly lab tests. Conclusion: CDC73 gene mutation-associated disorders are inherited as an autosomal dominant fashion, with variable penetrance. This gene mutation can be found in conditions such as hyperparathyroidism jaw tumor, familial hyperparathyroidism and parathyroid cancer.Reference:1.CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4534–4540.