Abstract

Human calcitonin (hCT) levels were measured in serum and urine samples from normal subjects and patients with medullary thyroid calcinoma (MCT) and non-thyroidal cancer (NTC). The immunological size-heterogeneity of calcitonin was examined in some of these samples.The hCT level in serum was measured directly by RIA and that in urine was measured after purification; that is, 2 ml of urine sample were boiled for 2 min, mixed with blue dextran and passed through a Bio Gel P-2 0.8 × 20 cm column, and the blue void volume was used for measurement of hCT.The hCT levels in the serum of 66 normal subjects ranged from less than 25 to 140 pg/ml, and those in the urine of 56 normal subjects ranged from 66 to 270 pg/mg creatinine (Cr). The hCT levels in the serum of 24 patients with MTC ranged from 0.24 to 215 ng/ml, and those in the urine of 11 of the 24 ranged from 1.7 to 520 ng/mgCr. In the 11 patients with MTC, the hCT levels in the urine (in ng/mgCr) were 3.4 to 20.8 times higher than those in the serum (in ng/ml), and these two levels were positively correlated with each other (r=0.93, p<0.001). The hCT levels in the serum of 277 patients with NTC ranged from less than 25 to 2013 pg/ml, and those of 44 patients (16%) with various kinds of non-thyroidal cancer were abnormally high (>150 pg/ml). The urine hCT levels of 82 of the 277 patients ranged from 60 to 83,000 pg/mgCr, and the levels of 16 patients (20%) were abnormally high (>300 pg/mgCr). In one patient with lung cancer, the serum and urine hCT levels were both abnormally high (1.8 ng/ml and 80 ng/mgCr, respectively), and an oat cell carcinoma of the lung was found at autopsy.On gel filtration on a Bio Gel P-30 1.5 × 80 cm column, four distinct forms of immunoreactive calcitonin were observed in serum samples from three patients with MTC; one was eluted in the same position as synthetic hCT and the other three in positions corresponding to higher molecular weights. The main form in urine samples from these three patients was eluted in a position corresponding to one form with higher molecular weight in the serum, not in the position of synthetic hCT. The serum sample from the patient with oat cell carcinoma of the lung contained three bigger forms of immunoreactive calcitonin, and no form eluted with synthetic hCT. A urine sample from this patient also contained one main form which was eluted as a bigger form similar to that of MTC patients.It was concluded that the measurement of urine hCT levels is useful not only for detecting cases of MTC but also of ectopic calcitonin secreting tumors, and that the urine of these patients contains a specific form that is bigger than synthetic hCT.

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