SAT-748 - Refractory Hypocalcemia Caused by Olaparib‑Induced Severe Hypomagnesemia in Metastatic Breast Cancer

Introduction:
Severe hypocalcemia is an uncommon but potentially life‑threatening electrolyte disorder, most often occurring secondary to impaired parathyroid hormone (PTH) secretion or action. Profound hypomagnesemia is a well‑recognized but frequently under-reported cause of refractory hypocalcemia. With increasing use of poly(ADP‑ribose) polymerase (PARP) inhibitors such as olaparib in BRCA‑mutated malignancies, rare metabolic complications are emerging. We report a case of olaparib‑associated severe hypomagnesemia resulting in refractory hypocalcemia requiring continuous intravenous calcium infusion, highlighting diagnostic and therapeutic challenges relevant to endocrinology practice.

Case:
A 67-year-old woman with BRCA1-positive, triple-negative metastatic breast cancer on olaparib presented with progressive weakness, muscle cramps, facial twitching, and inability to ambulate. Laboratory evaluation revealed severe hypocalcemia (total calcium 4.8 mg/dL; corrected ≈6 mg/dL), profound hypomagnesemia ( < 0.4 mg/dL), hypokalemia, and hypoalbuminemia. PTH was appropriately elevated (152 pg/mL), and vitamin D levels were 40 ng/mL, consistent with secondary hyperparathyroidism. Despite repeated intravenous calcium gluconate pushes of 1 g every 6 hours, totaling 9 g, hypocalcemia persisted with ongoing neuromuscular symptoms. Endocrinology was consulted for severe hypocalcemia and hypomagnesemia, and hypocalcemia was attributed to severe hypomagnesemia, likely induced by olaparib and compounded by chronic diarrhea and poor oral intake. The patient required a continuous calcium gluconate infusion (11 g in 1 liter of sodium chloride over 20 hours) with aggressive IV magnesium repletion, resulting in normalization of calcium and magnesium levels and resolution of symptoms. Olaparib was discontinued, and she was discharged on high-dose oral calcium and magnesium supplementation.

Discussion:
This case highlights the critical role of magnesium in calcium homeostasis and emphasizes that hypocalcemia refractory to bolus calcium therapy should prompt immediate evaluation for hypomagnesemia, as severe magnesium deficiency can impair parathyroid hormone secretion and induce peripheral PTH resistance PARP inhibitor–associated electrolyte disturbances may be severe, prolonged, and unrecognized, highlighting the need for heightened clinical awareness and routine monitoring in patients receiving these therapies. When hypocalcemia is driven by magnesium‑dependent PTH resistance, intermittent calcium pushes may be ineffective, and continuous intravenous calcium infusion may be required to achieve biochemical stability and symptom resolution. Well‑structured case reports remain essential for identifying novel drug‑related endocrine toxicities and helping clinicians apply these insights to real‑world practice.

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