Endocrine Abstracts

Introduction: The extracellular calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that is expressed in the parathyroids and kidneys, where it allows regulation of parathyroid hormone (PTH) secretion and extracellular calcium concentrations. Inactivating heterozyogous CaSR mutations result in familial benign hypocalciuric hypercalcaemia. However, the role of CaSR polymorphisms in controlling serum calcium, PTH and bone mineral density (BMD) remains controversial.

Case report: 35 years old patient presented with abdominal pain and vomiting. Standard investigations showed a moderate chronic hypercalcemia (2.80 mmol/l). Further analysis showed a mild hypophosphatemia (0.58 mmol/l), mild hypocalciuria (2.4 mmol/24 h), normophosphaturia (15.8 mmol/l) and a normal parathyroid hormone (PTH) level (32 ng/ml). Imaging studies did not show any parathyroid nodule or radio isotope fixation. BMD was normal. Family history showed a sister with persistent hypercalcemia even after parathyroidectomy of 2 parathyroid glands, her grandmother underwent parathyroidectomy of the 4 glands. Genetic screening for CaSR mutations did not show any deleterious mutation, indeed, a heterozygous variation (c3031 C>G P.Gln1011Glu) on the exon 7 of CaSR gene was determined.

Discussion: The CaSR coding region polymorphisms involve evolutionary conserved residues with amino acid substitutions. In our patient, the polymorphysm involves non conservative changes at codon 1011. In the literature, polymorphisms of CaSR are known to be benign without an impact on serum calcium and PTH. We demonstrate an association between a polymorphism in the coding region of CaSR gene and serum calcium, PTH, 25-hydroxyvitamin D, urinary calcium excretion. Indeed, this polymorphism does not affect the BMD. This polymorphism associated with alterations in the dose-response functional modification of the receptor to Ca+2 concentrations explaining this moderate hypercalcemia.

Conclusion: Although studies showed that polymorphisms did not produce significant alterations in calcium homeostasis, it is clear that phenotypes of these polymorphisms could be variable and hypocalciuric hypercalcemia is not unexpected.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.