Endocrine Abstracts

Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine disorder. However, a familial hyperparathyroid syndrome is diagnosed in less than 5% of cases. We present two related cases of CDC73-related familial hyperparathyroidism due to a rarely described germline Leu63Pro missense mutation in CDC73 exon 2.

Case report: The index patient, a 24-year-old female, presented acutely unwell with symptoms of hypercalcaemia. Her blood tests showed PTH 186.1 pmol/l (1.5–7.6) with calcium 4.20 mmol/l (2.2–2.6). Parathyroid imaging demonstrated bilateral parathyroid adenomas. Her life-threatening hypercalcaemia was treated with i.v. saline and bisphosphonates. However despite treatment with cinacalcet, persistent severe symptomatic hypercalcaemia necessitated an urgent parathyroidectomy. All four parathyroid glands were excised. Her recovery was complicated by severe hungry bone syndrome.

The patient’s parents are unaffected by hyperparathyroidism. However it transpired that her 35-year-old brother had a history of resected Wilms’ tumour aged 5. He also had PHPT with a left inferior parathyroid adenoma removed in 2008. Despite being initially lost to follow-up, he was subsequently re-referred with symptomatic recurrent PHPT (PTH 31.2 pmol/l, Ca 2.95 mmol/l). He underwent repeat parathyroid surgery and one normally functioning parathyroid gland was left in-situ. In both cases, parathyroid histology was benign. Genetic testing revealed germline Leu63Pro missense mutation in CDC73 exon 2.

Discussion: CDC73-related familial hyperparathyroidism encompasses a spectrum of parathyroid disorders including hyperparathyroidism-jaw tumour syndrome (HPT-JT). HPT-JT is an autosomal dominant condition with incomplete penetrance, characterised by atypical parathyroid tumours (~15% malignant) with tumours of one or more of the jaw, kidneys or uterus. Patients are at high risk of recurrent parathyroid and non-parathyroid tumours and require long-term surveillance. These particular cases demonstrate an unusual germline missense mutation of CDC73 in the same family but with variable phenotype.