Hypercalcemic crisis associated with anastrozole use in a patient with breast cancer and primary hyperparathyroidism

Excerpt

A 61-year-old woman was urgently referred to the endocrine clinic for hypercalcemic crisis. She had been diagnosed with mild primary hyperparathyroidism (PHPT) 16 months before (Fig. 1) with a 24-hour urine calcium level of 276 mg (normal <250 mg), and a 1.4 × 0.9 × 0.9-cm parathyroid nodule. A few months later, as she was contemplating on potential parathyroidectomy, mammogram screening detected lobular carcinoma in situ of the left breast; she deferred parathyroidectomy and underwent left breast lumpectomy. Her breast cancer was positive for estrogen receptor, progesterone receptor, and HER-2. After surgery, she received radiation without chemotherapy. Twelve and half months after she was diagnosed with PHPT, she started adjuvant hormonal therapy with anastrozole 1 mg daily. At that point, her serum calcium levels had ranged between 11.0 and 11.4 mg/dL (normal 8.4–10.2). One month after starting anastrozole, she complained of progressive fatigue. Two and a half months later (16 months from the original diagnosis of PHPT), she developed lethargy, polyuria, and polydipsia. Her workup revealed calcium level 16.5 mg/dL, creatinine 1.5 mg/dL (normal 0.4–1.2) (baseline 0.9), albumin 4.3 g/dL (3.4–5.0), and globulin 2.7 g/dL (2.4–3.5) (Fig. 1). Her past medical history also included multinodular goiter, hypothyroidism, and hypertension. There had been no changes in her regular medications including levothyroxine, ergocalciferol, amlodipine, atorvastatin, omega-3 fatty acids, and ramipril. The patient was admitted for hypercalcemic crisis. Further testing showed free calcium level 2.10 mmol/L (1.12–1.23), PTH 714.4 pg/mL, PTH-related protein (PTHrp) 0.2 pmol/L (normal <2), 25-hydroxyvitamin D 40 ng/mL (normal 30–100), 1,25-dihydroxyvitamin D 129 pg/mL (normal 18–72), and 24-h urine calcium 384 mg. Repeat thyroid ultrasound examination showed no change in the parathyroid nodule. Anastrozole was discontinued. She was treated with intravenous fluid, zoledronate 4 mg once, and calcitonin 350 units twice a day for 2 days. Her serum calcium and PTH levels decreased (Fig. 1). She underwent fine-needle aspiration of the parathyroid nodule and was discharged home. Cytological examination of the biopsy material confirmed the parathyroid origin. Seven weeks later, she underwent parathyroidectomy. Histological examination of the surgical specimen revealed hypercellular parathyroid gland with lesional cells within fibroconnective tissue and focal fibrous proliferation, which may be related to prior fine-needle aspiration. A year later, her calcium and PTH levels were both in the high-normal range.

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