A004 and OC4

A rare case of hypercalcemia in pregnancy- a diagnostic conundrum

T Ladha1, S. Khan, Z Hilal1, D Hirani1, M Moriarty1, M Tan2, V Bravis1, T Vakilgilani1, L Sykes2, C Yu2, J Cox1, S Robinson2, R. Agha-Jaffar1

St Mary’s Hospital 1Endocrinology 2Obstetrics Department, Imperial Healthcare NHS Trust,

Abstract: Hypercalcaemia in pregnancy is a rare but important phenomenon, given the potential associated risks to mother and baby. These include hypertension, pancreatitis, nephrolithiasis and renal failure in the mother and intrauterine growth restriction of the foetus, neonatal hypoparathyroidism/hypocalcaemia together with stillbirth (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 the age of 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 a pregnancy, her biochemistry was repeated, and her calcium was incidentally found to measure 3.55mmol/L (reference range 2.20- 2.60mmol/L, pre- pregnancy levels in the community 2.62mmol/-2.65mmol/L, PTH <0.2pmol/L). The patient was initially treated with intravenous fluids, encouraged to establish a low calcium diet and maintain hydration. In view of a creatinine of 122umol/L, renal obstetric input was sought, and an ultrasound demonstrated evidence of medullary nephrocalcinosis. Further investigations demonstrated the following: 25-OH Vitamin D 250 nmol/L, 1,25-OH Vitamin D 267pmol/L. PTH-Related Peptide and Fibroblast Growth Factor 23 are pending.

Subsequent targeted genetic testing demonstrated a compound heterozygous mutation in CYP24A1, confirming the diagnosis of idiopathic infantile hypercalcaemia (2).

This case is consistent with infantile idiopathic hypercalcaemia, a cause of PTH-independent hypercalcaemia. Hypercalcaemia in this individual was exacerbated by pregnancy-induced physiological changes, including increased vitamin D driven calcium absorption in the gut and 1-alpha hydroxylase expression by the placenta (1). With her diagnosis, maternal calcium of 3.55mmol/L and the possibility of fetal/neonatal hypoparathyroidism, she has been commenced on subcutaneous calcitonin with excellent response. She will require close monitoring and regular growth scans throughout pregnancy and the postpartum period.

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