Abstract: PO1472
CYP24A1-Hypercalcemia in Pregnancy
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Shaikh, Sana J., Barnes-Jewish Hospital, Saint Louis, Missouri, United States
- Vijayan, Anitha, Washington University in Saint Louis, Saint Louis, Missouri, United States
Introduction
Hypercalcemia due to primary hyperparathyroidism and malignancy is common. However, rare genetic mutations in VitD metabolism (CYP24A1 & SLC34A1) are often culprits.
Case Description
33-year-old woman with chronic hypercalcemia, nephrocalcinosis, CKD 3, HTN was admitted at 34-weeks of gestation for symptomatic hypercalcemia (13.2 mg/dL). Labs showed ↓PTH (9 pg/mL), ↓/↔25-VitD (35 ng/mL) & ↑/↔1,25-VitD (65 pg/mL). Defect in VitD pathway was suspected. 25-VitD:24,25-VitD ratio returned raised (178). Genetic testing confirmed compound heterozygous CYP24A1 mutation.
Discussion
CYP24A1 gene encodes 24-hydroxylase which inactivates 25-VitD and 1,25-VitD to 24,25-VitD and 1,24,25-Vit D. Biochemical profile includes ↑ serum & urinary calcium, ↓PTH, ↑25-VitD:24,25-VitD ratio +/- ↑ 1,25-VitD & 25-VitD. 25-VitD:24,25-VitD > 80 warrants genetic analysis.
Azoles inhibit 1-hydroxylase and ↓1,25-VitD, and can be utilized. Steroids ↓1,25-VitD production by activated macrophages, inhibit intestinal calcium absorption and induce CYP24A1, but this cohort is often resistant.
Pregnancy upregulates 1-hydroxylase, rendering patients with CYP24A1 mutations sensitive to hypercalcemia. Antepartum therapy options are limited. To limit adverse impact on maternal and fetal health, delivery may be required.
Maternal hypercalcemia with CYP24A1 mutations
| Reference | CYP24A1 Mutation | Comments | Pharmacological Treatment |
| Shah AD et al | Compound heterozygous | Gestational hypercalcemia x4 | - |
| Dinour D et al | Homozygous | Gestational hypercalcemia x3 c/b exogenous VitD + Ca during third pregnancy | D/c VitD + fluids, pamidronate, steroids |
| Kwong WT et al | Homozygous | Gestational hypercalcemia x2 | Fluids, calcitonin |
| Woods GN et al | Homozygous | Gestational hypercalcemia x2 c/b exogenous VitD + Ca | D/c VitD + fluids, calcitonin |
| Hedberg F et al | Compound heterozygous | Sister I: gestational hypercalcemia x4 and postpartum hypercalcemia x1; sister II: gestational hypercalcemia x2 | Sister I: fluids, furosemide, calcitonin, pamidronate; Sister II: fluids |
| McBride L et al | Homozygous | Gestational hypercalcemia x2 | Fluids, calcitonin, steroids |
| Arnold N et al | Compound heterozygous | Gestational hypercalcemia c/b exogenous VitD | Fluids, furosemide, steroids during pregnancy + postpartum denosumab |
| Arnold N et al | Homozygous | Postpartum hypercalcemia in the third pregnancy c/b exogenous VitD + Ca | Fluids, steroids, pamidronate, zoledronic acid, denosumab |
| Macdonald C et al | Compound heterozygous | Gestational hypercalcemia in 1 of 2 pregnancies c/b exogenous VitD | D/c VitD + short trial of steroids without response |