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 (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 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, 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 TSH=1.50-0.059 x 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 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, 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.