E-Poster Presentation ESA-SRB-ANZBMS 2021

Severe Hypercalcaemia in Pregnancy and Lactation – Like Mother, Like Baby? (#374)

Emma E Croker 1 , Yvette Mikaheal 1 , Kindelan Murray 2 , Helen MacCallum 3 , Hong Lin Evelyn Tan 1 2 , Ailsa Borbolla Foster 4 , Judy Luu 1 2 , Katie Wynne 1 2
  1. Department of Endocrinology, John Hunter Hospital, New Lambton, NSW, Australia
  2. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  3. Department of General Medicine, John Hunter Hospital, NEW LAMBTON,NSW, NSW, Australia
  4. Department of Maternal Fetal Medicine, John Hunter Hospital, NEW LAMBTON,NSW, NSW, Australia

This case contributes to the limited literature on severe PTH-independent hypercalcaemia during pregnancy and lactation. A 38-year-old primiparous woman presented in early pregnancy with a 6-year history of intermittent mild PTH-independent hypercalcaemia and elevated 1,25-hydroxyvitamin D (1,25VitD) level without identified cause (Figure 1a) or suspicion of calcitriol use.

In early second trimester she developed severe PTH-independent hypercalcaemia (corrected calcium 3.38mmol/L (range 2.1-2.6)) that persisted during her pregnancy (Figure 1b). Her third trimester PTHrp was elevated 42.27pmol/L (non-pregnant range <1.0) with a 1,25VitD (835pmol/L) twice the expected pregnancy range. She had minimal response to intravenous fluids and did not respond to 10-day high-dose glucocorticoid. A modest response to strict low calcium diet (<150g per day) was observed. There was no evidence of end-organ damage until development of pre-eclampsia at 36-weeks.  A healthy infant was delivered via emergency caesarean-section at 37-weeks gestation. Maternal hypercalcaemia persisted post-partum and worsened with establishment of lactation. Fluconazole (1-alpha reductase inhibitor) was commenced in attempt to reduce 1,25VitD but ultimately severe hypercalcaemia (3.53mmol/L) necessitated cessation of lactation with subsequent rapid improvement of calcium levels. Initial neonatal hypercalcaemia (day 8 corrected calcium 3.08mmol/L (range 1.85-2.8)) resolved by day 14 post-partum.

Pregnancy and lactation-induced significant elevation of 1,25VitD and PTHrp postulated to be driving the PTH-independent hypercalcaemia although underlying aetiology remained under investigation; a post-partum FDG-PET was non-diagnostic. Similar biochemical and clinical pattern are well-reported in rare cases of 24-hydroxylase loss-of-function mutations. Genetic testing for CYP24A1 mutations are pending.

Key points:

  • Differential diagnosis, investigation and management of severe PTH-independent hypercalcaemia in pregnancy and lactation
  • Counselling women of child-bearing age regarding the potential course of pre-existing hypercalcaemic disorders during pregnancy
  • Consideration of genetic testing for CYP24A1 mutation in long-standing undifferentiated PTH-independent hypercalcaemia with elevated 1,25VitD
  • Clinical features and management of CYP24A1 mutation

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