the Dilemma of Aggressive Vitamin D Replacement in Refractory Hypercalcemia of Malignancy and Severe Vitamin D Deficiency
Presentation Number: MON 328
Date of Presentation: April 3rd, 2017
Hongxiu Luo*1, Nikki Duong2, Mari Suzuki3, Shirisha Avadhanula4, Jacqueline Jonklaas5 and Laura Cowen6
1NIH-NICHD, Bethesda, MD, 2George Washington University, Washington, 3National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD, 4Medstar Georgetown University/Washington Hospital Center, Washington, DC, 5Georgetown University, DC, 6MedStar Georgetown University Hospital, Washington, DC
Hypercalcemia of malignancy can occur as a result of multiple different mechanisms, including parathyroid related-peptide (PTHrP), osteolytic hypercalcemia, ectopic calcitriol, and ectopic PTH production. Vitamin D deficiency is known to induce secondary hyperparathyroidism due to decreased calcium and increased bone turnover. Thus, adequate vitamin D replacement is recommended for patients with both primary and secondary hyperparathyroidism. In the cases of refractory hypercalcemia of malignancy and concurrent severe vitamin D deficiency, the clinical dilemma arises regarding the role of Vitamin D replacement .
We present a case of a patient with hypercalcemia of malignancy and severe vitamin D deficiency who was given vitamin D replacement. The patient is a 54 year-old African American female with clear-cell ovarian cancer status post total abdominal hysterectomy and bilateral salpingo-oophorectomy without chemotherapy or radiation, with multiple metastases (bladder, vertebral body L3-L5 and peritoneal lymph nodes). She presented to the hospital with nausea, malaise and severe constipation, and was found to have acute pancreatitis. Her blood pressure was 86/45 mmHg with a heart rate of 130 beats/minute. Lab tests revealed a calcium level of 14.9 mg/dL(normal range 8.0-10.4 mg/dL), ionized calcium 1.66 mg/dL ((normal range 4.25-5.25 mg/dL)), albumin 2.3 g/dL (normal range 3.5-5.5 g/dL), corrected calcium 16.26 mg/dL. Her PTHrP was 8.8 pmol/L (normal is negative), with suppressed PTH 6.3 pg/mL (normal range 10-65 pg/mL). Her lipase peaked at 2724 u/L (normal range 4-25 U/L). She received aggressive intravenous hydration with 0.9% NaCl 250 ml/hr, 3 courses of subcutaneous calcitonin 200 units twice daily. She also received the second dose of Pamidronate 60 mg IV (first dose about 1 week ago). Her pancreatitis symptoms improved after one week. After three weeks, her lab work revealed persistent hypercalcemia (corrected calcium level 12.11 mg/gL) and severe vitamin D deficiency with 25-(OH) vitamin D level less than 6 ng/mL(normal 20-40 ng/mL) . At that time, she was treated with a dose of Denosumab 120 mg subcutaneous injection and vitamin D3 5000 IU by mouth every day. The repeated tests one week after she received Denosumab and vitamin D3 showed a serum calcium level improved to 7.4 mg/dL (albumin 1.8 g/dL, ionized ca 1.08 mg/dL, with corrected calcium 9.16 mg/dL).
In conclusion, this patient’s severe hypercalcemia was induced by elevated PTHrP, causing extra-renal production of 1,25-(OH)D and osteolytic metastasis in the vertebral bone. Vitamin D3 replacement did not worsen the hypercalcemia during a one-week observation. However, the concern about potential effect of long term vitamin D replacement on refractory hypercalcemia of malignancy and the lack of clinical guidelines regarding vitamin D replacement in such cases warrant more evidence-based studies.
Nothing to Disclose: HL, ND, MS, SA, JJ, LC