Clinical usefulness of a new chemiluminescent two-site immunoassay for human calcitonin

The introduction of two-site immunoassays has greatly improved the measurement of human calcitonin (CT). But even within the two-site assays differences in sensitivity and ease of performance are noted. We evaluated the clinical usefulness of a new sensitive chemiluminescence two-site immunoassay for CT (Nichols) in comparison to an established two-site elisa (Medgenix). The range of measurement spans from 0.7 to 2500 pg/ml after 4h incubation for the chemiluminescent assay, compared to 2.0 to 1000 pg/ml after overnight incubation for the elisa. We investigated 179 healthy subjects (55 males, 124 females) to assess the upper limit of normal for CT values obtained by the chemiluminescence assay, which was defined as the 95th percentile of the distribution. The values obtained were 6.55 pg/ml for males and 4.13 pg/ml for females (p < 0.0005, Mann Whitney test). After pentagastrin-stimulation of 19 healthy volunteers (9 male, 10 fe male), the upper limit of normal for pentagastrin-stimulated CT was found at 43.0 pg/ml for males and 36.8 pg/ml for females (p < 0.05, Mann Whitney test). CT values obtained in patients with proven medullary thyroid carcinoma (MTC) or in subjects with suspected familial disease were positively correlated between both two-site assays (rho 0.961, p < 0.0001, Spearman rank correlation). More importantly the results led to the same clinical decision (normal vs, elevated) in 92.5% (37 of 40) patients. In all three patients with discordant results, clinical follow up supported the decision based on the chemiluminescence assay. Pentagastrin stimulation tests in MTC patients and localization studies of occult MTC tissue by selective venous catheterization led to concordant results in both assays. The new Nichols chemiluminescence assay demonstrated advantages in handling, a lower detection limit and a slightly higher sensitivity than the Medgenix elisa. CT values obtained by the chemiluminescence assay were on average 1.4-fold lower, which may be due to a slightly superior specificity of the assay although this problem was not specifically addressed in this study. The clinical usefulness of both assays is highly satisfactory. In all cases, however, where clinically meaningful differences occurred, follow up proved the results obtained with the chemiluminescence assay to be correct.