A CASE OF SQUAMOUS-CELL LUNG-CARCINOMA WITH HIGH-CONCENTRATION OF PARATHYROID HORMONE-RELATED PEPTIDE IN SERUM AND PLEURAL EFFUSION PRESENTING HYPERCALCEMIA

A 57-year-old man with lung squamous cell carcinoma revealed hypercalc emia, hypophosphoremia, elevation of nephrogenous cAMP and metabolic a lkalosis. Serum parathyroid hormone (PTH) and 1,25(OH)2D3 concentratio ns were not elevated. These findings were consistent with those in hum oral hypercalcemia of malignancy (HHM). PTH-related peptide (PTHrP) co ncentrations were determined using N- and C-terminal specific radioimm unoassays (PTHrP-N, PTHrP-C), and elevation of both PTHrP-N and PTHrP- C concentrations in the serum was noted (PTHrP-N, 27 pmol/liter (norma l<5); PTHrP-C, 1408 pmol/liter (normal<50)). High concentration of PTH rP (946 pmol/liter for PTHrP-N and 5983 pmol/liter for PTHrP-C) was al so found in the pleural fluid obtained at autopsy. Immunohistochemical study, using paraffin-embedded sections of the tumor tissue obtained at autopsy, revealed numerous PTHrP-positive cells and expression of P THrP gene was confirmed by Northern blot analysis. These findings indi cate that PTHrP, produced in the tumor tissue, was secreted into the b lood stream, which caused HHM in the patient. Gel permeation chromatog raphy of the serum and pleural fluid revealed several peaks of both PT HrP-N and PTHrP-C. Molecular forms of PTHrP-N were larger than those o f PTHrP-C in the serum as well as pleural fluid. These findings indica te that multiple forms of PTHrP molecules are present in the serum and pleural fluid. Granulocytosis was also noted in the patient. However, granulocyte- and granulocyte macrophage-colony stimulating factor wer e not detected in the serum, and the mechanism of the granulocytosis i n the patient was unclear.