A-050 Understanding the Complex Relationship Between TSH and Free Thyroxine

Abstract

Abstract Background Guidelines suggest screening for thyroid disease using thyroid stimulating hormone (TSH) first before free thyroxine (fT4) since there is an inverse log-linear relationship between them; the signal favors TSH over fT4 in a ratio of >100:2. We reassessed this fT4 to TSH relationship following the improved 3rd generation TSH assay from Roche (since 09/2019). Methods Consecutive paired TSH/fT4 (n = 7484) from distinct ambulatory non-hospitalized subjects that were assayed on cobas e801 were retrieved from our laboratory information system and combined with similar data from Kuala Lumpur Hospital (n = 11 369) that were assayed on cobas e601. Reference intervals and measuring limits for the Roche assays were 0.4–4.0 μIU/L and 0.005–100 μIU/L for TSH, and fT4 10–20 pmol/L and 0.3–100 pmol/L for fT4, respectively. Values outside the reportable limits (n = 618) were excluded. Descriptive statistics, linear and nonparametric (kernel) regression were performed using the statistical software packages in R 4.2.0. Results Linear regression of logTSH against fT4 (n = 18 235) gave an r = −0.35. Nonparametric regression revealed two negative sigmoid curves merging into the euthyroxinemic region (see Graph). Three different segments can be discerned; hypothyroxinemic (fT4 < 10): logTSH = 1.91–0.136fT4 (n = 422; r = −0.39, P < 0.001), euthyroxinemic (fT4 10–20): logTSH = 0.672–0.028fT4 (n = 15 754, r = −0.13, P < 0.001), and hyperthyroxinemic (fT4>20): logTSH = 1.106–0.055fT4 (n = 2059, r = −0.33, P < 0.001). Conclusion The relationship between fT4 and TSH is complex. The widely accepted view of a constant gradient of logTSH against fT4 over the whole range of thyroid test values is inaccurate. Three distinct relationships correspond to each biochemical thyroid status. In the hypothyroxinemic and hyperthyroxinemic range, TSH increases almost 5-fold and 13-fold with a doubling of fT4, respectively. In the euthyroxinemic range, there is no relationship between logTSH and fT4. While a TSH first strategy is applicable in hypo/hyperthyroxinemia, both TSH/fT4 are still required to confirm diagnoses and for baseline assessment prior to commencing therapy.