Endocrine Abstracts

Parathyroid hormone-dependent hypercalcaemia is one of the commonest conditions seen in endocrinology clinics. Primary hyperparathyroidism (PHPT) is the usual cause although some cases are due to other conditions including familial hypocalciuric hypercalcaemia (FHH). Making the distinction between PHPT and FHH is important in order to avoid unnecessary parathyroid surgery. Urinary calcium quantification is an integral part of diagnostic investigations. We present the case of a 28 year lady who was suspected to have delayed growth as early as nine months of age. She was found to have significant hypercalcaemia (more than 3.0 mmol/l), hypophosphataemia and hyperparathyroidism but, apart from bothersome constipation, remained largely asymptomatic in childhood. She had no obvious family history of hypercalcemia. Further investigations showed normal vitamin D and urinary calcium with no evidence of renal calcification on imaging. Genetic testing for FHH revealed no mutation in CaSR gene. Further testing revealed a heterogeneous mutation of R15L in AP2S1 gene, confirming a diagnosis of FHH type 3. At 24 years of age, a DEXA revealed osteopenia. She is currently under close endocrine surveillance with regular clinical assessments, biochemical monitoring for hypercalcaemia and hypercalciuria, renal imaging for nephrocalcinosis/nephrolithiasis and monitoring of bone mineral density. FHH is an autosomal dominant condition. Genetic defects in FHH result in reduced calcium sensing by parathyroid receptors with compensatory hypercalcemia and inappropriately low to normal urinary calcium. Patients are usually asymptomatic and require no active treatment. Mutation of the AP2S1 gene is a recognised cause of FHH type 3 and patients may have significant hypercalcaemia with non-suppressed parathyroid hormone. Cinacalcet has been successfully used in some FHH type 3 patients with symptomatic hypercalcaemia but there is no evidence that it has long term beneficial effects on bones or kidneys.