Simultaneous PTHrp- and calcitriol-mediated hypercalcemia associated with probable spontaneous transformation of lung adenocarcinoma to squamous cell carcinoma: A case report

Hypercalcemia is a common paraneoplastic syndrome. Malignancies cause hypercalcemia by various mechanisms. Usually a single mechanism underlies paraneoplastic hypercalcemia. Two simultaneous mechanisms associated with one malignancy, however, are occasionally encountered. Here a rare case is reported to describe simultaneous PTHrp- and calcitriol-mediated hypercalcemia associated with probable spontaneous transformation of lung adenocarcinoma to squamous cell carcinoma. This 81-year-old male with history of resected lung adenocarcinoma developed hypercalcemia. The peak albumin-corrected calcium was 13.4 mg/dL (normal 8.6-10.4) with ionized calcium 1.70 mmol/L (normal 1.09-1.29). Laboratory tests showed PTH 7 pg/ml (normal 11-51), PTHrP 43.7 pmol/L (normal <2.3), 25-hydroxyvitamin D 33 ng/ml (normal 20-50), 1,25-dihydroxyvitamin D 71.0 pg/ml (19.9-79.3), TSH 3.1 <mu>IU/mL (normal 0.3-4.7). CT showed new right lower lobe lung masses, paraesophageal and pericaval lymph nodes, and a cranial lesion. Biopsy of a lung mass revealed predominantly squamous cell carcinoma. He was treated with intravenous fluid and zoledronate with normalization of calcium levels. Vitamin D supplement was discontinued. The patient's clinical condition deteriorated before chemotherapy was started. He died shortly after comfort care was initiated. Pursuing multiple causes of paraneoplastic hypercalcemia is worthwhile as the treatment towards each mechanism is different.