Parathyroid hormone-related peptide induced hypercalcemia of pregnancy due to mammary hyperplasia

Maternal Parathyroid Hormone-related Protein (PTHrP) is involved in the placental transport of calcium. Autonomous overproduction of PTHrP is a rare cause of hypercalcemia in pregnancy. Prior cases of PTHrP-induced hypercalcemia in pregnancy have been managed with either dopamine agonists, fetal delivery, termination of pregnancy, or mastectomy. However, PTHrP level normalization following mastectomy has not previously been documented. Herein, we present a 39-year-old female hospitalized at 19 weeks of gestation for acute encephalopathy due to PTHrP induced hypercalcemic crisis (calcium 15.8 mg/dL, PTHrp 46.5 pmol/L [normal 0-3.4]). Mammary hyperplasia resulting in gigantomastia significantly impaired her ability to ambulate and perform activities of daily living. She remained hypercalcemic during hospitalization despite aggressive hydration, calcitonin, and 2 weeks of dopamine agonist treatment. Bisphosphonate therapy was not administered due to pregnancy and potential effects on the fetus. Our patient underwent bilateral mastectomy along with excision of a large axillary mass. The pathology of all three specimens revealed mammary stromal hyperplasia. PTHrP was undetectable on post-op day 2 and calcium normalized by post-op day 3. At discharge, she was able to ambulate independently. To our knowledge, this is the first reported case of PTHrP induced hypercalcemia related to gigantomastia, documenting resolution of hypercalcemia, and PTHrP levels following mastectomy. Mastectomy is a potential option in the second trimester for pregnant patients with PTHrP induced severe hypercalcemia due to gigantomastia, refractory to treatment with dopamine agonist therapy. Parathyroid Hormone-related Protein (PTHrP) is important for transportation of calcium during pregnancy, facilitating fetal skeleton formation. Rarely, excess production of PTHrP can cause critically elevated calcium levels in pregnancy. We present a 39-yr-old female hospitalized at 19 wk of gestation for altered mental status, due to PTHrP-induced hypercalcemic crisis. She demonstrated profound breast enlargement and a left axillary mass, impairing her ability to walk and work. Despite aggressive hydration, and medical treatment targeted to lower calcium, her calcium remained significantly elevated. She underwent surgical removal of both breasts and excision of the axillary mass which each demonstrated mammary stromal hyperplasia. PTHrP levels became undetectable, and calcium quickly normalized. To our knowledge, this is the first reported documentation of resolution of hypercalcemia and PTHrP levels following surgical resection of the excess breast enlargement during pregnancy. Graphical Abstract