Humoral hypercalcemia of pregnancy treated with bisphosphonates

Abstract

Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.

Non-parathyroid hypercalcemia during lactation: a case report

“…Although breastfeeding osteoporosis may be related to an increase in PTHrP, the specific mechanism of PTHrP leading to breastfeeding osteoporosis is still unclear (18). However, according to the correlation between PTHrP, breastfeeding osteoporosis, and hypercalcemia, we speculated that the treatment of lactation in this patient could reduce lactation and inhibit the secretion of PTHrP in the breast, which might improve hypercalcemia and its related symptoms.…”

A Scoping Review of the Apparent Phenomenon of the Improvement in Hypoparathyroidism in Pregnant and Postpartum Females

“…Authors, such as Sato [ 55 ], suggested that the PTHrP hypersecretion leading to hypercalcemia during pregnancy was of placental origin. Koren et al [ 57 ] presented a 38-year-old female without hypoparathyroidism developing hypercalcemia during pregnancy (12.7 mg/dL), alongside suppressed PTH; the authors suggested that this is likely due to PTHrP hypersecretion from the placenta (not measured) and noted significant resistance to conventional treatment (loop diuretics, isotonic saline, and calcitonin), requiring management with pamidronate (levels normalized postpartum). Of note, the authors do not mention whether the patient breastfed following delivery.…”

Bisphosphonates, Old Friends of Bones and New Trends in Clinics

“…86 Case studies have reported the utility of BPs in pediatric hypercalcaemia secondary to Williams Syndrome 87 and in humor hypercalcaemia of pregnancy. 88 The antihypercalcaemic use of BPs is only discouraged in patients with renal failure, because the kidney is the main organ of BP elimination from the body (see the Pharmacology of Biphosphonates section), and it is already fragile in these patients due to the effort of calcium elimination. 85 Bone Scintigraphy.…”

“…Some of the patients that required repetition of treatment with BPs showed signs of drug resistance, with only partial reduction of calcium levels, but nonetheless they had significant improvements in symptomatology and increased lifespan . Case studies have reported the utility of BPs in pediatric hypercalcaemia secondary to Williams Syndrome and in humor hypercalcaemia of pregnancy . The antihypercalcaemic use of BPs is only discouraged in patients with renal failure, because the kidney is the main organ of BP elimination from the body (see the Pharmacology of Biphosphonates section), and it is already fragile in these patients due to the effort of calcium elimination…”