Hypocalcemia in Setting of Malignancy of Unknown Origin: A Case Report

Background: Hypercalcemia is a common finding well-recognized in up to 30% of cases of malignancy, associated with poor prognosis and advanced disease state. Hypocalcemia, while uncommon, can also be found in cases of malignancy facilitated by its own unique mechanism and etiologies. We present a case of severe hypocalcemia in the setting of malignancy of unknown origin. Clinical Case: 72-year-old female with a history of metastatic carcinoma of unknown origin, followed actively by Oncology, presented acutely with shortness of breath, chest pain, stiff hands and clenched fist. Patient had reported a 20 lbs weight loss over three months with a “knot” in the epigastric area affecting appetite and interfering with eating. Prior CT showed diffuse adenopathy with diffuse permeative bone destruction highly suspicious for malignancy. Follow up PET-CT showed mixed lytic lesion and sclerotic changes throughout the entire skeleton from the skull to mid thighs compatible with osseous metastatic. Initial tests show severe hypocalcemia with appropriately PTH elevation and normal vitamin D25 (calcium 5.5 mg/dL, albumin 3.9 g/dL, phosphorus (PO4) 2.3 mg/dL, magnesium (Mg) 1.5 mg/dL, PTH 243 pg/mL, vitamin D25 31.44 ng/mL). Further workup shows normal creatinine levels (0.88 mmol/L) and elevated alkaline phosphatase (1140 IU/L). Physical exam revealed bilaterally clenched fist and positive Chvostek sign. After two doses of 2 grams calcium gluconate, calcium had improved up to 7.2 mg/dL (corrected 7.76 mg/dL, albumin 3.3 g/dL) with plans to replete Mg and PO4. Patient was started on Calcium-Vitamin-D 500-200 mg-units (Oscal) two tabs trice daily. However, calcium continues to drop the next day with levels at 5.7 mg/dL (corrected 6.42 mg/dL, albumin 3.1 g/dL). A calcium infusion of 10 grams was then given over 16 hours. Calcitriol 0.25 mg twice daily was started. 24-hour urine study showed low calcium excretion (<0.8 mg/dL), normal Mg excretion (6.5 mg/dL) with an adequate creatinine collected (0.6 grams) showing no deficiencies in kidney resorption. Prior to discharge, patient’s calcium had stabilized (corrected 8.2 mg/dL, albumin 3.4 g/dL) and her associated symptoms had resolved. She was discharged on Oscal 2 tabs 4 times daily and Calcitriol 1 mcg twice daily. Conclusion: Given these biochemical results and imaging evidence of bone metastases, this case highlights the uncommon findings of hypocalcemia in the setting of malignancy. With the combination of low 24-hour urine calcium, elevated PTH, normal vitamin D25, low PO4, normal kidney function and increased alkaline phosphatase, these findings most likely indicate hypocalcemia secondary to osteoblastic bone metastasis, resulting from deposition of calcium in osteoblastic lesions. References: Schattner A, Dubin I, Huber R, Gelber M. Hypocalcaemia of malignancy. Neth J Med. 2016 Jul;74(6):231–9. PMID: 27571720