Endocrine Abstracts

Hypercalcaemia in pregnancy is a rare but important finding, given the associated potential risks to mother and baby. These include hypertension, pancreatitis, nephrolithiasis and renal failure in the mother and intrauterine growth restriction, neonatal hypoparathyroidism/hypocalcaemia and stillbirth in the baby (1). We present the case of a 26-year-old female with a background of PTH-independent hypercalcaemia of unknown aetiology. This was initially detected at age 6 months when she was investigated for frontal bossing in Poland. Relevant family history includes that of her two siblings who have chronic kidney disease with renal cysts. Following confirmation of pregnancy, her biochemistry revealed an adjusted calcium of 3.55 mmol/l (her pre-pregnancy levels were 2.62 mmol/l-2.65 mmol/l) (reference range 2.20–2.60 mmol/l) and a PTH of < 0.3 pmol/l (reference range 1.6–7.2 pmol/l). She was initially treated with intravenous fluids, encouraged to establish a low calcium diet and subsequently maintain oral hydration. In view of a creatinine of 122 umol/l (reference range 55–110 umol/l), renal obstetric input was sought, and an ultrasound demonstrated medullary nephrocalcinosis. Further investigations demonstrated the following: 25-OH Vitamin D 250 nmol/l (reference range 70–150 nmol/l), 1.25-OH Vitamin D 267 pmol/l (reference range 55–139 pmol/l) and Fibroblast-Growth-Factor-23 240 H RU/ml (reference range < 100 H RU/ml). PTH-Related-Peptide results are pending. Subsequent targeted genetic testing demonstrated a compound heterozygous mutation in CYP24A1, resulting in hypercalcaemia due to excess active vitamin D metabolites (2). To address persistent maternal hypercalcaemia ( > 3.00 mmol/l with conservative measures) and reduce the risk of perinatal hypoparathyroidism, she was commenced on subcutaneous calcitonin from 20 weeks gestation (intermittent dosing of 50–100 units repeated when calcium > 2.80 mmol/l). She is now 32 weeks gestation and undergoing close monitoring with regular biochemistry and growth scans, given the risk of growth restriction associated with hypercalcaemia. Here we describe a rare but important cause of hypercalcaemia and its exacerbation and management in pregnancy. Maternal hypercalcaemia was worsened by pregnancy-induced physiological changes, including increased vitamin D-driven calcium gut absorption as well as 1-alpha hydroxylase placental expression (1). An excellent response to calcitonin therapy has resulted in calcium levels safely maintained between 2.55–2.67 mmol/l during pregnancy.

References

1. Arnold N. et al. (2019). Intractable hypercalcaemia during pregnancy and the postpartum secondary to pathogenic variants in CYP24A1. Endocrinology, Diabetes & Metabolism Case Reports, 2019. doi: 10.1530/EDM-19-0114.

2. Schlingmann KP. et al. (2011). Mutations in CYP24A1 and Idiopathic Infantile Hypercalcemia. New England Journal of Medicine, 365(5), pp. 410–421. doi: 10.1056/NEJMoa1103864.