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

Abstract

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 o250 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 o 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.The patient was earlier diagnosed with mild PHPT, and her calcium levels had been only mildly elevated 3.5 months before the hypercalcemic crisis. Mild PHPT invariably progresses very slowly; a sudden and significant increase in calcium levels is highly unusual. The concurrent elevation of PTH and calcium levels after anastrozole use suggests that the worsening PHPT is likely caused by anastrozole. As PTH levels in patients with PHPT typ...

Effects of honey supplementation on safety profiles among postmenopausal breast cancer patients

“…Postmenopausal breast cancer women had increased creatinine levels with acute kidney failure after administration of anastrozole for 3 months in one report 38 . Similarly, increased creatinine levels in breast cancer patients were observed after administration of anastrozole for 1 month, indicating the adverse effects of anastrozole 39 . Hence, it is plausible that the increased creatinine levels in both the control and honey groups observed in our study might be due to progressive adverse effects of anastrozole.…”

Challenges of Differential Diagnosis Between Primary Hyperparathyroidism and Bone Metastases of Breast Cancer

“…Although the mechanisms for tamoxifen flare hypercalcemia remain unclear, studies suggest it as a frequent complication of anti-estrogen therapy. 7 , 25 On the other hand, osteolytic hypercalcemia is usually associated with decreasing PTH due to overproduction of PTHrP, resulting in calcium renal retention. 2 , 3 …”

“…Although the mechanisms for tamoxifen flare hypercalcemia remain unclear, studies suggest it as a frequent complication of anti-estrogen therapy. 7,25 On the other hand, osteolytic hypercalcemia is usually associated with decreasing PTH due to overproduction of PTHrP, resulting in calcium renal retention. 2,3 Vitamin D deficiency might be considered as a risk for breast cancer and PHPT since this steroid hormone is associated with induction of apoptosis and negative impact on cancer cell proliferation.…”

“… 5 , 6 PHPT might be asymptomatic, normocalcemic, or with an unusual presentation, causing no specific symptoms; and therefore, it might escape from the early diagnosis and subsequently cause severe complications. 4 , 5 , 7 , 8 Bone loss should always be considered in patients with breast cancer due to hormone-ablative therapy. 9 , 10 On the other hand, the bone is a frequent site of breast cancer distant metastases, accompanied by hypercalcemia, but not with the elevated PTH.…”