Pilot study on the assessment of the setpoint of the hypothalamus–pituitary–thyroid axis in healthy volunteers

Abstract

Objective: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT 4 ) combination in each individual. Subjects and methods: Twenty-one healthy volunteers (nine males and 12 females; mean age 60 years, range 51-74) were randomized to receive at 2300 h with 2-week intervals a single dose of placebo, 125 mg T 4 and 250 mg T 4 (arm 1, nZ10), or placebo, 25 mg triiodothyronine (T 3 ) and 50 mg T 3 (arm 2, nZ11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT 4 and T 3 . Results: Intra-and inter-individual variation and the individuality index of the four baseline serum samples were respectively 21.6%, 41.9% and 0.52 for TSH; 9.9%, 16.5% and 0.60 for FT 4 ; and 9.3%, 16.0% and 0.58 for T 3 . Substantial differences existed in the location of individual working points within the reference range. T 4 administration increased FT 4 (but not T 3 ) and decreased TSH, resulting in a log-linear relationship (log TSHZ1.50-0.059!FT 4 , P!0.05) for the whole group. T 3 administration increased T 3 and decreased TSH (but not FT 4 ), resulting in a log-linear relationship (log TSHZ0.790-0.245!T 3 , P!0.001) for the whole group. Log-linear relationships were not always significant when assessed for each subject separately. Conclusion: Individuality indices of TSH, FT 4 and T 3 are all %0.6, thereby limiting the usefulness of the population-based reference values. Accurate assessment of individual setpoints of the HPT axis was not possible with the applied single doses of T 4 or T 3 , and will require either prolonged administration or higher single doses of thyroid hormone.

Ghrelin affects the hypothalamus–pituitary–thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma

“…It can be argued that the TSH suppression observed in our study might be caused by a feedback inhibition by fT 4 . Both the plasma half-life of TSH of roughly 1 h and our finding that the relative increase of fT 4 was about four times weaker than the relative decrease of TSH seem to be in line with this assumption since TSH and fT 4 have been shown to have an inverse log-linear relationship (41,42). However, it is questionable whether the small increase of fT 4 can entirely explain the distinct and sustained suppression of TSH as several times stronger increases of fT 4 after administration of 125 or 250 mg T 4 in healthy volunteers failed to be associated with a significant decrease of TSH (41).…”

“…While regular administration of T 4 causes an increase of T 3 since more T 4 will be deiodinized to T 3 (56, 57), short-term administration of T 4 is not necessarily associated with changes in T 3 (41). Comparably, the small T 4 increase observed in our study was not followed by higher T 3 plasma levels.…”

Thyrotropin Isoforms: Implications for Thyrotropin Analysis and Clinical Practice

“…The usefulness of population-based TSH reference intervals to detect thyroid dysfunction in individuals may be somewhat limited (43,44). This is because it has been demonstrated that for TSH the between-person variability is more variable than within-person variability (45)(46)(47).…”

The log TSH–free T4 relationship in a community‐based cohort is nonlinear and is influenced by age, smoking and thyroid peroxidase antibody status

“…4 An inverse, log-linear relationship between TSH and T4 became a central tenet of thyroid physiology and has served as a basic assumption in a diverse range of studies. [5][6][7][8][9][10] Three recent cross-sectional studies suggested that the log-linear relationship between TSH and T4 is incorrect, or at best an over-simplification. In an analysis of thyroid function tests from two laboratory data sets of 3223 and 6605 individuals, Hoermann et al reported that the log TSH-free T4 relationship was more accurately described by a nonlinear model based on the error function (ERF) than by a linear relationship.…”