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 mu g T-4 and 250 mg T-4 (arm 1, n=10), or placebo, 25 mu g triiodothyronine (T-3) and 50 mu g T-3 (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, FT4 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 FT4; 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 FT4 (but not T-3) and decreased TSH, resulting in a log-linear relationship (log TSH=1.50-0.059 x FT4, P<0.05) for the whole group. T-3 administration increased T-3 and decreased TSH (but not FT4), resulting in a log-linear relationship (log TSH=0.790-0.245 x 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, FT4 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.