Peripheral autoregulation of thyroxine to triiodothyronine conversion in man

This study describes the existence of a peripheral tissue mechanism for maintaining serum T3 concentrations in states of T4 deficiency or excess in man. Serum T3 and T4 levels were determined in 242 primary hypothyroid subjects who had been maintained on varying doses of oral T4 therapy. Subjects treated with sub-maintenance T4 doses were supplemented by additional oral T3 therapy to maintain eumetabolic status as assessed by suppression of serum TSH values. This T3 supplementation was withdrawn 4-5 days prior to study in order to obviate any influence on serum T3 indices. Serum total T3/T4 ratio values in this study population were observed to progressively decline fivefold in a curvilinear manner as serum T4 concentrations rose from less than 0.5 to 20 micrograms/dl (total serum T3/T4 ratio fell from approximately 50 to 10, ng T3/ng T4 X 10(3)). This phenomenon is presumably the result of an altered T4 to T3 conversion by peripheral tissue 5'-deiodinase systems. A similar alteration of T4 to rT3 conversion with changing serum T4 levels does not appear to occur since serum rT3/T4 ratios did not vary in a separate study population over a serum T4 concentration span from 4-16 micrograms/dl. The mechanism by which this autoregulatory control of T4 to T3 conversion occurs is unknown. However, it would appear physiologically to complement the pituitary-thyroid autoregulatory system by acting to defend and maintain serum T3 concentrations in states of T4 deficiency and excess.