An Unusual Case of Hypercalcemia

By Laurence (Ned) Kennedy, MD, and Karla Arce, MD

History and presentation

A 28-year-old woman who had recently given birth was referred to our Endocrine Calcium Clinic for newly noted hypercalcemia. She had been diagnosed with DiGeorge syndrome when she was 6 weeks old, after presenting with seizures. Hypoparathyroidism was confirmed at that time, and she had been treated with calcium and calcitriol at various doses over the years.

During the pregnancy, her medication dosages had required frequent adjustments. Prior to evaluation at our clinic, she was taking 0.25 mcg of calcitriol daily, 12.5 mg of hydrochlorothiazide (HCTZ) daily, 250 mg of magnesium three times a day (TID) and 750 mg of calcium carbonate TID.

The pregnancy was uncomplicated. She delivered a baby girl at term and began breast-feeding immediately. At that time, her serum calcium was 8.6 mg/dL (8.5-10.1 mg/dL), phosphorus was 3.4 mg/dL (2.5-2.9 mg/dL) and magnesium was 1.6 mg/dL (1.7-2.4 mg/dL). Two weeks postpartum, the patient’s serum calcium had increased to 12.7 mg/dL, at which time she was referred to our clinic.

Evaluation and treatment

We decreased the calcitriol to 0.25 mcg every other day. Six weeks later, she remained hypercalcemic (13.1 mg/dL), so calcium carbonate was stopped and the 0.25 mcg of calcitriol was decreased to every three days. She continued to breastfeed for 12 months and her calcitriol requirements gradually increased, reaching pre-pregnancy levels within days of weaning at 13 months post-partum.

Discussion

DiGeorge syndrome is a rare condition caused by an embryologic defect in the development of the third, fourth and fifth branchial pouches. One of its major manifestations is hypoparathyroidism.

Maternal hypoparathyroidism may change during pregnancy due to increased intestinal absorption of calcium; this may be mediated by 5-dihydroxyvitamin D due to parathyroid hormone-related peptide (PTHrP) secretion from the placenta and the myometrium. High concentrations of PTHrP have been found in human breast milk, and this may be the principal factor involved in the transfer of calcium from the mammary glands to milk. There is evidence that PTHrP secretion depends strongly on the action of prolactin.

This case illustrates the importance of monitoring serum calcium closely in patients with hypoparathyroidism during pregnancy and, particularly, lactation. Calcitriol requirements of hypoparathyroid women fall early in the postpartum period, especially if the woman breast-feeds, and hypercalcemia may occur if the calcitriol dosage is not reduced.

Dr. Arce is a former fellow in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic.