Endocrine Abstracts

Background: Significant changes in calcium metabolism occur during normal pregnancy to meet the needs of the growing fetus. These include a rise in 1,25-dihydroxyvitamin D (1,25-(OH)D₂ and consequent suppression of parathyroid hormone (PTH). In spite of this, maternal hypercalcaemia is very uncommon and should prompt further investigation.

Clinical case: A 24-year-old primigravida woman was referred for assessment of maternal hypercalcaemia. She was well with no history of nephrolithiasis or nephrocalcinosis. Of note, monthly cholecalciferol supplementation had been commenced just prior to the pregnancy. At 13 weeks’ gestation corrected calcium was 2.9 mmol/L (2.2–2.6), PTH 0.7 pmol/L (1.6–7.0), and urine calcium:creatinine 2.09 mole ratio (0.06–0.45). 25-hydroxyvitamin D was 116 nmol/L (50–150) and 1,25-(OH)D₂ was significantly elevated at 380 pmol/L (65–175). Vitamin D supplementation was stopped. Hypercalcaemia persisted throughout the remainder of the pregnancy with minimal symptoms and a healthy, normocalcaemic infant was born at 38 weeks’ gestation. Breast feeding was not established and maternal plasma calcium returned to the normal range at 10 days post-partum. However, hypercalciuria persisted and renal tract ultrasound showed unilateral nephrolithiasis. Analysis of the CYP24A1 gene identified a compound heterozygote state with E143Del and K351Nfs*21 mutations. Family screening and genetic counselling is now underway.

Conclusion: Hypercalcaemia in pregnancy is rare and the differential diagnosis should include an underlying disorder of 1,25-(OH)D₂ metabolism. Compound heterozygote or homozygous mutations in CYP24A1 may result in hypercalcaemia and hypercalciuria, particularly in states such as pregnancy, and supplemental vitamin D should be avoided. At other times, with this condition calcium may be normal although hypercalcuria often persists. Monitoring these patients for complications including nephrocalcinosis and nephrolithiasis is recommended.