Evidence for Dual Peripheral 5’Deiodinases (5’D) Regulating Circulating T₃ Levels in Man

Abstract

The majority of circulating T₃ in euthyroid man appears to be derived from conversion of T₄ to T₃ via 5’deiodinase (5’D) systems located in peripheral tissues. Recently, we have reported that a progressive reduction in the efficiency of T₄ to T₃ conversion occurs when circulating T₄ levels rise from subnormal to supraphysiological concentrations (1,2). As shown in Fig. 1 (left panel), the greatest change in conversion efficiency of T₄ to T₃ is seen over the span of T₄ values ranging between 0 and 5 µg/dl in eu-TBG-emic subjects. These data were obtained in 254 patients who had been placed on varying doses of chronic T₄ therapy. Some of the T₃ values in patients with identical serum T₄ levels have been averaged in order to obtain a better overview of the mean pattern of the T₃ response in the study population. In separate T₄ tracer kinetic studies, we have found that a 50% conversion efficiency of T₄ to T₃ occurs at low serum T₄ values which progressively drops to less than 15% at T₄ levels in excess of 20 µg/dl (3).It is of interest that no apparent alteration in the efficiency of T₄ to rT₃ was detected over this same range of serum T₄ values (2).

Supported in part by USPH Grant AM11727, USPH Training Grant AM07119, and DRR General Clinical Research Center Grant RR-43.