Hypercalcemia with
adult T-cell leukemia (ATL) is chiefly caused by an excessive production by
tumor cells of
parathyroid hormone-related protein (
PTHrP). We have previously reported hypercalcemic patients with solid
tumors to excrete a large amount of the C-terminal fragments of
PTHrP (C-
PTHrP) into their urine. To elucidate whether
PTHrP production correlates with or predicts the development of
hypercalcemia, we studied the urinary excretion of C-
PTHrP in 36 ATL patients. The urinary excretion of C-
PTHrP was in the normal range (< 0.40 nmol equivalent to
PTHrP (109-141)/g
creatinine) in HTLV-1-positive carriers (n 3), ATL patients
in complete remission (n 2) and chronic type ATL patients (n 2). It was marginally increased in seven patients in partial remission, and gradually increased as the disease progressed. In 20 patients who died without or with
hypercalcemia, it was increased to 1.98 +/- 0.69 (n 9) and 7.6 +/- 2.1 nmol/g
creatinine (mean +/- SD, n 11, P < 0.01), respectively. Urinary C-
PTHrP excretion was significantly correlated with serum
calcium and LDH levels as well as with CD25-positive cells in the peripheral blood. In four patients whose urinary excretion had been serially determined, it increased prior to the development of
hypercalcemia. The findings suggest the urinary excretion of C-
PTHrP to be of use as a predictor of the development of
hypercalcemia in ATL patients. In ATL patients whose urinary excretion of C-
PTHrP is progressively increasing, the serum
calcium concentration should be carefully monitored to prevent hypercalcemic crisis.