(11.10) Hypercalcemia During Pregnancy: Unraveling Fractures and Stones

A 25-year-old woman was evaluated for multi-level vertebral compression fractures and kidney stones occurring in the post-partum period.

Case(s) Description :

A 25-year-old woman delivered a healthy child, and 2 months later began experiencing lower back pain which acutely worsened when she was lifting her baby's car seat. She had an MRI due to worsening pain, which revealed 9 non-traumatic compression fractures of her thoracic vertebra. DEXA scan revealed Z scores of L-spine, hips, and femoral neck within normal limits. The patient was referred for endocrine evaluation as the fragility fractures suggested a clinical picture of osteoporosis. The patient also reported that she had a history of 4 kidney stones during the latter half of her pregnancy. Lab testing was relevant for 25-hydroxy vitamin D 49.2 ng/mL, calcium 11.9 mg/dL, parathyroid hormone (PTH) 6 pg/mL, parathyroid hormone-related protein (PTHrP) 0.5 pmol/L, 24-hour urine calcium 378 mg/24 hr (expected range 100-300). Renal function, TSH, and T4 were within normal limits. Her clinical history and labs were most consistent with hypercalcemia and resultant fractures and nephrolithiasis related to PTHrP elevation in the setting of pregnancy.

Discussion :

This young patient experienced multi-level vertebral fractures with low trauma mechanism of injury as well as multiple kidney stones in the peripartum period, with labs revealing hypercalcemia and low PTH. PTHrP is a protein that shares structural homology with PTH. Aberrant elevations of PTHrP during pregnancy are rare and can lead to hypercalcemia. The exact mechanism underlying this condition may involve enhanced production of PTHrP by placental trophoblasts and mammary glands, resulting in increased renal calcium reabsorption and bone resorption. It is thought that the rapidity of bone loss in this process is associated with fractures, despite normal Bone Mineral Density (BMD) values. Even modest PTHrP elevation has been associated with symptoms and is exacerbated by breastfeeding. This patient’s normal PTHrP level may be explained by the fact that it was collected several months after cessation of her pregnancy and breastfeeding. After the patient discontinued lactation, she proceeded to have an improvement in back pain, no new fractures, and no further kidney stones, suggesting that conservative management to reduce the release of PTHrP by stopping breastfeeding was effective. This case is unique in its possible mechanism of hypercalcemia through excess PTHrP production in pregnancy and lactation. Interdisciplinary collaboration and further research is needed to elucidate further management strategies for this uncommon obstetric complication.