Endocrine Abstracts

A 29 year-old nursing student, was incidentally detected to have high serum calcium 3.43 mmol/l (2.2-2.6) whilst being treated for community acquired pneumonia. She had no symptoms of hypercalcaemia. Her uncle had been operated for primary hyperparathyroidism (PHPT) although only limited details were available. PTH of 28 pmol/l (1.6-7.2) confirmed the diagnosis of PHPT. She had vitamin D deficiency, normal liver and renal function. She was offered parathyroidectomy and preoperative neck ultrasound and radio-nuclide scan (MIBI with SPECT) were concordant for right lower parathyroid adenoma. In view of the young age, genetic tests were arranged. Analysis of all the coding regions and exon/intron boundaries of the MEN1 gene by Sanger sequencing did not reveal any pathogenic mutation. Further dosage analysis of the AIP, CDKN1B and MEN1 genes by multiplex ligation dependent probe amplification did not detect partial or whole gene deletion. During elective parathyroidectomy intraoperative PTH dropped to < 50% and histology confirmed parathyroid adenoma. Over the next 4 years, she maintained normocalcaemia and normal PTH. 5 years later and 12 months after the last normal serum calcium value she presented with hypercalcaemia (3.15 mmol/l) and PTH 31.16 pmol/l confirming recurrence of PHPT. Localisation scans were concordant for left lower parathyroid adenoma. Extended genetic testing confirmed partial gene deletion of CDC73 gene which is linked to autosomal dominantly inherited PHPT, hyperparathyroidism-jaw tumour syndrome and renal lesions (cysts, renal hamartomas and rarely Wilm’s tumour). After local and regional discussion, left unilateral neck exploration is planned after providing the patient with a full explanation of the decision and possibility of further neck surgery. This patient raises several interesting features about genetic testing in a patient with PHPT, complex decision making about surgical approach, CDC73 related manifestations and implications for family and off-springs.