The calcium-sensing receptor (CaSR) is a G-protein coupled receptor expressed in the parathyroid gland and kidneys. Loss of function mutations of the CaSR result in familial hypocalciuric hypercalcaemia (FHH). Rarer, gain of function mutations of the CaSR result in hypercalciuric hypocalcaemia and are inherited in an autosomal dominant pattern. The phenotype varies from asymptomatic individuals, to profound hypocalcaemia. We present a severely affected individual whose case highlights the potential pitfalls in treatment of hypercalciuric hypocalcaemia and a novel therapeutic approach with a continuous parathyroid hormone (PTH) infusion. A 16 year old, Caucasian female was referred to our unit with severe hypocalcaemia and frequent fits. She was born at 31 weeks gestation and aged 2 days old was noted to be hypocalcaemic, hypomagnesaemic and hypoparathyroid. The patients mother had hypocalcaemia since childhood and an initial diagnosis of familial hypoparathyroidism was made. Genetic analysis aged 4 years identified a heterozygous missense CaSR mutation and she was diagnosed with hypercalciuric hypocalcaemia. Her medication included sandocal, magnesium, alfacalcidol and bendrofluazide. Biochemistry: Corr Ca++1.42.9 mmol/l, creatinine 101 μmol/l. Renal ultrasound:early nephrocalcinosis. A trial of subcutaneous PTH 134 20 μg bd and cessation of alfacalcidol/bendrofluazide, resulted in improved hypercalciuria, but persistent hypocalcaemic fits. She was thus trialled on a continuous PTH infusion, via an insulin pump (omnipod, unlicensed use) at 1.3 μg/h (concentration 125 μg/ml) resulting in a stable serum calcium, with no fits for 1 year. She was converted to a Medtronic pump due to supply issues and developed hypercalcaemia, requiring a reduction in PTH to 0.735 μg/h (concentration 35 μg/ml). This case demonstrates the potential severity of hypercalciuric hypocalcaemia and the very difficult balance between avoiding hypocalcaemic seizures and hypercalciuria-associated nephrocalcinosis. It highlights the importance of avoiding vitamin D in this condition, which worsens hypercalciuria and nephrocalcinosis. Our patient has impaired renal function and her mother has end stage renal failure. This case demonstrates the dramatic clinical improvement and smaller PTH doses that can be achieved with a continuous PTH infusion. It also shows the potential variability in PTH delivery between different insulin pumps.
01 Jan - 31 Dec 2017
Society for Endocrinology