Endocrine Abstracts

Introduction: Approximately 5-10% of PHPT cases are hereditary. One such hereditary cause of PHPT is Hyperparathyroidism-jaw Tumour Syndrome (HPT-JT) caused by an autosomal dominant mutation in cell division cycle 73 (CDC73) that impairs parafibromin, a protein with antiproliferative activity. HPT-JT is characterised by parathyroid tumours, ossifying jaw fibromas, renal tumours and uterine tumours. We report a familial case of HPT-JT caused by a novel CDC73 mutation.

Case presentation: A 52-year-old female with a biochemistry consistent with PHPT (aCa 2.65 mmol/l, PTH 21.2 pmol/l, Vit D 88.5 nmol/l) was referred to our Endocrine Bone Unit. Of note, she previously had a 2-gland parathyroidectomy at the age of 30 at a different institution, hysterectomy for fibroids/polyps in her 40’s and previous renal calculi. Ultrasound and nuclear medicine imaging of the neck suggested a left-sided parathyroid adenoma. Her bone mineral density was normal and there was no evidence of nephrolithiasis/nephrocalcinosis on imaging. A detailed family history revealed that her 37-year-old daughter underwent parathyroidectomy at the age of 24 for PHPT and consequently developed hypoparathyroidism as a complication. An x-ray orthopantomogram showed a cemento-fibro-osseous lesion in the daughter only. Genetic testing was carried out in both mother and daughter and revealed a novel heterozygous CDC73 missense variant in GRCh37 (hg19) (Chr1: g.193091353T>G). This variant has not been reported in the gnomAD database (~125,000 individuals) and may represent a de novo mutation. Additional family members have been diagnosed with PHPT and therefore family segregation analysis is underway. Our patient was managed conservatively, with close monitoring of her biochemistry and for potential dental and renal complications.

Conclusions: Screening for CDC73 germline mutations is important in patients with early-age onset PHPT and a family history of PHPT as well as in patients uncured by surgery.