A Case Report of Patient With Mysterious Hypercalcemia

Background: Non-parathyroid hormone related hypercalcemia has a broad differential diagnosis. One of the key diagnosis to exclude is malignancy. Case: A 41 yo male with paraplegia due to an accident at age 21, b/l BKA, stage 4 sacral pressure ulcer complicated by vesico-cutanous fistula status post ileal conduit and chronic osteomyelitis of the ischia, sacrum and pelvis was admitted with sepsis secondary to infected sacral pressure ulcer. He was noted to be hypercalcemic with corrected calcium of 13.4mg/dl. He had no previous history of hypercalcemia, kidney stones, head or neck radiation. Work up showed appropriately suppressed PTH with normal PTHrp, 1,25-dihydroxy vitamin D, 25-dihydroxy vitamin D, SPEP, UPEP and TSH. Drug induced hypercalcemia was ruled out. CT abdomen/pelvis was done and showed chronic osteomyelitis; destruction of the sacrum, ischia, pubic bones and femoral heads with enlarged inguinal lymph nodes. Review of records showed a NM bone scan done the year prior to admission to evaluate the chronic destruction of pelvic bones was negative for malignancy. Chest imaging was unremarkable. Patient underwent debridement and wash out of sacral and bilateral lower extremity wounds with bone biopsy. Pathology showed necrotic bone, chronic and acute inflammatory tissue. Calcium peaked at 17mg/dl prior to bisphosphonate, calcitonin and IVF becoming effective. Given the severity of hypercalcemia there was concern for malignancy despitethe negative work up thus Interventional Radiology was consulted for lymph node biopsy. Inguinal lymph node FNA was positive for metastatic squamous cell cancer prompting an exam under anesthesia which was negative for anal lesions. He underwent a cystoscopy which showed a large fungating mass involving the bulbar and membranous urethra with biopsies consistent with invasive and moderately differentiated keratinizing squamous cell carcinoma. Hypercalcemia resolved with treatment and he was discharged home to complete an antibiotic course prior to anticipated chemotherapy. Unfortunately, patient died prior to starting chemotherapy. Conclusion: Hypercalcemia has been found to be associated with 30% of late stage malignancies and is a marker of poor prognosis. It is most commonly associated with hematological malignancies, such as multiple myeloma and leukemias as well solid tumors like breast carcinomas. In Hypercalcemia of malignancy, PTHrp is the causal agent in over 80% of cases with 20% of cases attributed to osteolytic mechanisms mediated by inflammatory cytokines. Less than 1% of hypercalcemia of malignancy is attributed to excess 1,25-dihydroxy vitamin D. High level of suspicion for malignancy should be presentwhen patients present moderate/severe non-PTH mediated hypercalcemia. Workup for malignancy should be pursued even with normal PTHrp.