Pilot study on the assessment of the setpoint of the hypothalamus- pituitary-thyroid axis in healthy volunteers
Objective: To determine the log-linear relationship between TSH and free thyroxine in healthy subjects, and the variation in baseline TSH/free thyroxine (FT4) 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 μg T4and 250 mg T4(arm 1, n = 10), or placebo, 25 μg triiodothyronine (T3) and 50 μg T3(arm 2, n = 11). Blood samples were taken in the morning (0800-1100 h) before and following the administration of the drug for the assessment of TSH, FT4and T3. 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 FT4; and 9.3%, 16.0% and 0.58 for T3. Substantial differences existed in the location of individual working points within the reference range. T4administration increased FT4(but not T3) and decreased TSH, resulting in a log-linear relationship (log TSH = 1.50-0.059xFT4, P<0.05) for the whole group. T3administration increased T3and decreased TSH (but not FT4), resulting in a log-linear relationship (log TSH = 0.790-0.245xT3, 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, FT4and T3are 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 T4or T3, and will require either prolonged administration or higher single doses of thyroid hormone.