Estimates of circulating monomeric calcitonin: physiological studies in normal and thyroidectomized man.

To avoid the limitations of present human calcitonin (hCT) assays, we have developed a silica extraction and concentration method for plasma hCT that lowers the detection limit of the assay 40-fold (to 0.5-1.0 pg/ml), and markedly improves specificity of the assay for the CT monomer (hCT-M). Extraction recoveries of radioiodinated and unlabeled synthetic hCT-M added to 20 ml plasma were, respectively, 90 +/- 1% and 99 +/- 4% (mean +/- SE). Gel filtration chromatography of plasma from patients with medullary thyroid carcinoma demonstrated that the extract was markedly enriched in hCT-M. Basal plasma immunoreactive hCT was measured before (iCT) and after extraction (exCT) in 60 normal individuals; basal exCT levels were higher in young men than in young women [8.0 +/- 0.8 (+/- SE) vs. 4.6 +/- 0.5 pg/ml; P less than 0.001] and higher in elderly men than in elderly women (9.4 +/- 0.8 vs. 4.7 +/- 0.6 pg/ml; P less than 0.05), but not different with age. Calcium infusions (2 mg Ca/kg over 5 min) in 36 subjects showed a significantly greater secretory capacity for exCT in men than in women, but showed no decline of exCT response with age. There was no correlation between basal iCT and exCT concentrations, but there was a good correlation between peak Ca-stimulated iCT and peak Ca-stimulated exCT levels (r = 0.94; P less than 0.001), suggesting that hCT-M was the main form released by acute stimulation. The mean extractable CT level in 6 totally thyroidectomized individuals was 2.7 +/- 0.3 pg/ml and did not increase after Ca challenge. We found no significant differences in basal or Ca-stimulated exCT levels measured in 5 women on 3 different occasions over the span of 1 menstrual cycle. After a meal, exCT levels did not change in women, but there was a consistent increase in the men (28 +/- 7% over baseline at 3 h; P less than 0.01). In summary, plasma concentrations of exCT and, most likely, hCT-M were very low (less than 10 pg/ml in most healthy adults) and always increased after calcium infusion. The measurement of plasma exCT is a useful technique that provides new sensitivity and specificity for the study of hCT physiology.