Hepatocellular carcinoma presenting as hypercalcemia
Viji Das LM, Honasoge M, and Sulanc E. Hepatocellular carcinoma presenting as hypercalcemia. Endocr Pract 2018; 24:139-140
Objective: Humoral hypercalcemia is commonly seen associated with squamous cell cancers and breast cancers, but is also reported in other cancers. This is usually mediated through parathyroid hormone-related peptide (PTH-rP). PTH-rP interacts with the PTH/PTH-rP receptor that activates renal calcium reabsorption and promotes resorption of calcium from the bone. Hepatocellular carcinoma (HCC) may present with paraneoplastic syndromes and hypercalcemia was reported in 4-7% of patients. HCC presenting with hypercalcemia without bone metastasis is uncommon. We present one such case along with the discussion of mechanism of hypercalcemia. Case Presentation: 67 year old woman with a history of intravenous drug abuse and alcohol abuse presented with confusion, epigastric pain and generalized weakness of 2 week duration. Her vital signs were normal. She appeared drowsy and was oriented to person only. A magnetic resonance imaging of the brain ruled out a cerebrovascular event. Her labs showed ionized calcium 1.50 (1.0 - 1.35 mmol/L), intact parathyroid hormone 14 (15 - 65 pg/ mL), PTH-rP 39 (14 - 27 pg/mL), 25 hydroxy vitamin D 10 (> 20 ng/mL), 1, 25 dihydroxy vitamin D 24 (20 - 74 pg/mL), alkaline phosphatase 153 (0 - 140 IU/L), creatinine 0.53 (< 1.16 mg/dL) and GFR 110 (> 60 ml/ min/1.73m2). Liver function tests were abnormal and hepatitis C antibody was positive. Computed tomography of the abdomen revealed nodular cirrhotic liver with a 10 x 10 cm right hepatic mass compatible with HCC. She had elevated alpha fetoprotein and cancer antigen 19-9 levels. Due to hepatic cirrhosis, initially she was treated with gentle intravenous hydration with no improvement in calcium levels. Ionized calcium worsened to 1.90 mmol/L. She received intravenous zoledronic acid without significant improvement in her calcium levels and mental status. She is planned for further cancer directed therapy. Conclusion: 80% of hypercalcemia in cancer patients is estimated to be PTH-rP mediated. However, additional mechanisms that cause bone resorption or decreased renal excretion may be responsible. Bisphosphonates inhibit osteoclast bone resorption, and are used for paraneoplastic hypercalcemia associated with malignancy because of their favorable efficacy and lower toxicity. Refractory hypercalcemia has been reported in patients with HCC as noted in our patient. The PTH-rP level in our case was not very high in contrast with the expected direct association between severity of hypercalcemia and degree of PTH-rP elevation suggesting other contributing factors. We believe immobilization and volume contraction were the other driving mechanisms for her refractory hypercalcemia.