Serum Basal Thyroglobulin Measured by a Second-Generation Assay Correlates with the Recombinant Human Thyrotropin–Stimulated Thyroglobulin Response in Patients Treated for Differentiated Thyroid Cancer

Abstract

Recombinant human thyrotropin (rhTSH) stimulation is frequently used to assess the disease status of patients treated for differentiated thyroid cancer (DTC) when basal (unstimulated) thyroglobulin (b-Tg) is below the assay sensitivity limit. The objective of this study was to determine relationships between the b-Tg and the 72-hour rhTSH-stimulated Tg (rhTSH-Tg) using a second-generation immunochemiluminometric assay with a functional sensitivity of 0.05 ng/mL (microg/L). Serum Tg was measured in paired b-Tg and rhTSH-Tg specimens from 1029 rhTSH tests performed on 849 TgAb-negative patients during long-term monitoring for DTC. Basal Tg correlated with rhTSH-Tg across b-Tg concentrations ranging from 0.05 to 1000 ng/mL (microg/L) (r = 0.85, p < 0.0001). The b-Tg concentration was unrelated to age, sex, basal TSH, 72-hour TSH, or the Tg fold response (rhTSH-Tg/b-Tg). Further, only 2/655 (0.3%) tests with b-Tg below 0.1 ng/mL (microg/L) had rhTSH-Tg above 2.0 ng/mL (microg/L) (2.9 and 3.8 ng/mL [microg/L], respectively). Thirty-three patients with three or more rhTSH tests performed over a 2- to 5-year period displayed high indexes of individuality for both the 72-hour TSH and the Tg fold response (indexes of individuality = 0.30 and 0.38, respectively). Basal Tg measured using a first-generation assay with a functional sensitivity of 0.9 ng/mL (microg/L) failed to reliably detect an rhTSH-Tg response above 2.0 ng/mL (microg/L). An rhTSH-Tg response above 2.0 ng/mL (microg/L) was highly unlikely when b-Tg was below 0.1 ng/mL (microg/L). Second-generation b-Tg measurements correlated with the degree of rhTSH-Tg stimulation and thus the likelihood of having rhTSH-Tg above the customary cut-off of 2.0 ng/mL (microg/L), whereas b-Tg measured by a first-generation assay did not. Correlations between four different assays showed that the use of a fixed Tg cut-off was influenced by assay selection. Patients receiving repetitive rhTSH tests had highly reproducible rhTSH-Tg/b-Tg fold responses, suggesting that repetitive testing is unnecessary and that second-generation measurement of b-Tg trends without rhTSH stimulation would be satisfactory for the long-term monitoring of most patients with DTC.