Introduction: Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign, inherited condition caused by inactivating mutations in the calcium-sensing receptor (CASR) gene. Both FHH and primary hyperparathyroidism (PHPT) are characterized by elevated P-calcium, normal or elevated plasma-parathyroid hormone (P-PTH), and typically normal renal function. In PHPT, vitamin D metabolism is typically characterized by low plasma levels of 25-hydroxyvitamin D (25OHD), and high plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D). In FHH, the vitamin D metabolism is not very well known.
Objective: To compare and evaluate plasma 25OHD, 1,25(OH)(2)D, and PTH in FHH and PHPT.
Design: Cross-sectional study.
Materials: About 66 FHH patients with mutations in the CASR gene, 147 patients with surgically verified PHPT, and 46 controls matched to FHH patients according to age (+/-5 years), sex, and season. All patients had a P-creatinine <140 micromol/l.
Methods: We measured P-calcium, P-Ca(2)(+), P-albumin, P-creatinine, P-phosphate, P-magnesium, and P-PTH by standard laboratory methods. P-25OHD and P-1,25(OH)(2)D were measured by RIA or enzyme immunoassay. In FHH, all protein-coding exons in the CASR gene were sequenced and aligned to GenBank reference sequence NM_000388.2.
Results: PHPT patients had higher body mass index (2p<0.01), together with higher P-PTH (2p<0.01) and P-1,25(OH)(2)D (2p<0.01) compared with FHH patients. The groups had similar levels of P-Ca(2)(+) and of P-25OHD. The phenotypic expression of the CASR mutations (as determined by the degree of hypercalcemia) did not influence the levels of P-1,25(OH)(2)D.
Conclusion: Even though P-calcium and P-25OHD were comparable, P-1,25(OH)(2)D and P-PTH differed between FHH and PHPT.