ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 P51

A calcium sensing receptor mutation associated with hypercalcaemia and recurrent pancreatitis

Lesley Hall1, Dairena Gaffney2, Joanne Ramsay2, Andrew Gallagher1 & John Hinnie1

1Diabetes Centre, New Victoria Hospital, Glasgow, UK; 2Department of Biochemistry, Glasgow Royal Infiirmary, Glasgow, UK.

A 29-year-old man of South Asian descent presented with pancreatitis. Adjusted calcium was 3.10 mmol/l and PTH 9.8 μmol/l. Of note was that his parents were first cousins, and a cousin had undergone parathyroidectomy for hypercalcaemia.

Pituitary, adrenal and thyroid function, calcitonin, prolactin, phosphate, magnesium, alkaline phosphatase and urinary catecholamines were all normal. 25-Hydroxyvitamin D was 20 nmol/l (15–100) The patient was therefore commenced on ergocalciferol, 0.25 mg daily. Urinary calcium excretion was low at 0.5 mmol/24 h (2.50–7.50). Parathyroid imaging was normal.

Calcium sensing receptor (CASR) sequencing showed a C>T mutation 10 bps before the CASR start codon. This created an ATG sequence which could be a premature out-of-frame start codon. The patient was homozygous for this mutation while both parents and all 5 siblings were heterozygous and had normal serum calcium concentrations. The patient went on to have several further episodes of pancreatitis associated with hypercalcaemia, following which he was commenced on cinacalcet. Serum calcium gradually decreased and he remained well for 18 months. Unfortunately thereafter he had further episodes of pancreatitis and hypercalcaemia, suggesting non-compliance with cinacalcet or loss of drug effect.

Three years after initial presentation he underwent total parathyroidectomy. Parathyroid histology was normal. Postoperatively, he was commenced calcium carbonate and alfacalcidol. He went on to have a further episode of pancreatitis with hypercalcaemia, but with a PTH of only 0.8 μmol/l. Following this alfacalcidol dose was reduced and calcium carbonate discontinued. Since then he has not experienced further hypercalcaemia. However, he continues to have intermittent pancreatitis which is felt to be due to pancreatic duct stenosis.

We discuss the possibility that the mutation detected leads to a lack of functioning receptor and thus hypercalcaemia.

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