Complications in the Management of Hypercalcemia in a Patient with Systemic Lupus Erythematous and Lupus Nephritis During Pregnancy

Introduction:
Hypercalcemia can present with a multitude of symptoms including anorexia, nausea and vomiting, constipation and neuropsychiatric disturbances. There is an overlap in these symptoms with those experienced during both pregnancy and in systemic lupus erythematosus. This case report highlights the difficulties in the diagnostic evaluation and management of hypercalcemia during pregnancy.

Case Description:
A 26-year-old female with history of Systemic lupus erythematosus (SLE) complicated by Class V lupus nephritis and antiphospholipid syndrome presented August 2022 with symptomatic hypercalcemia at 8 weeks gestation. The patient reported fatigue, nausea and vomiting and new onset severe constipation, polydipsia and polyuria. Lab work was notable for hypercalcemia with calcium 13.2 mg/dl (corrected 13.7 mg/dl for Albumin 3.4 g/dl) and parathyroid hormone (PTH) 153 pg/ml. No parathyroid nodules were seen on ultrasound and 1st trimester ultrasound demonstrated a single live intra-uterine pregnancy. The patient was diagnosed with primary hyperparathyroidism and started on 0.9% normal saline intravenous fluid at 200 cc/hr and Furosemide 20 mg/Q6H IV to promote diuresis. Despite this, calcium could not be lowered to less than 12.4 mg/dl (13.0 mg/dl albumin corrected). The patient was discharged with instructions to drink 3-4 L water per day and take Furosemide 20 mg daily. On follow up at 14 weeks, Calcium was still elevated at 11.9 mg/dl and reported intermittent vomiting and constipation. ENT was consulted to consider parathyroidectomy however opted for conservative management of hypercalcemia prior to delivery due to inability to localize an adenoma and exclude ectopic parathyroid on imaging. The patient was followed closely for the remainder of her pregnancy with improvement in her symptoms, however continued to have persistent hypercalcemia posing risk of materno-fetal complications.

Discussion:
Treatment for hypercalcemia is based upon the severity and symptoms, but it is important to consider gestational age. Exceeding the upper normal limit of calcium during pregnancy of 9.5 mg/dL increases the risk of fetal complications including spontaneous abortion, still birth and neonatal tetany. There is added difficulty in determining true symptomatic hypercalcemia given the overlap in symptomatology with pregnancy. In pregnant patients undergoing parathyroid surgery, localization can be done with ultrasound rather than Sestamibi but risks missing ectopic parathyroid glands. If surgery is not recommended, there are limited therapeutic options during pregnancy for hypercalcemia. Notably, IV fluids and diuretics provide modest temporary benefit. Total serum calcium is reported to decline across gestation, likely due to plasma volume expansion, and this may temporize the harmful effects of hypercalcemia to defer surgery until after birth. There is inadequate data on the safe use of Cinacalcet during pregnancy with no known risk of teratogenicity reported in case reports. There is however an increased risk of neonatal hypocalcemia due to gestational suppression of the fetal parathyroid glands.