Peripheral Serum Thyroxine Triiodothyronine and Reverse Triiodothyronine Kinetics in the Low Thyroxine State of Acute Nonthyroidal Illnesses

摘要

The low thyroxine (T4) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T4 and triiodothyronine (T3) with elevated reverse T3 (rT3) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T4, T3, or rT3 were determined in 16 patients with the low T4 state and compared with 27 euthyroid controls and a single subject with near absence of thyroxine-binding globulin. Marked increases in the serum free fractions of T4 (0.070±0.007%, normal [nl] 0.0315±0.0014, P < 0.001), T3 (0.696±0.065%, nl 0.310±0.034, P < 0.001), and rT3 (0.404±0.051%, nl 0.133±0.007, P < 0.001) by equilibrium dialysis were observed indicating impaired serum binding. Noncompartmental analysis of the kinetic data revealed an increased metabolic clearance rate (MCR) of T4 (1.69±0.22 liter/d per m², nl 0.73±0.05, P < 0.001) and fractional catabolic rate (FCR) (32.8±2.6%, nl 12.0±0.8, P < 0.001), analogous to the euthyroid subject with low thyroxine-binding globulin. However, the reduced rate of T4 exit from the serum (Kii) (15.2±4.6 d⁻¹, nl 28.4±3.9, P < 0.001) indicated an impairment of extravascular T4 binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T4 to sites of disposal as reflected by the increased fractional disposal rate of T₄ (0.101±0.018 d⁻¹, nl 0.021±0.003, P < 0.001). The decreased serum T₃ binding was associated with the expected increases in MCR (18.80±2.22 liter/d per m², nl 13.74±1.30, P < 0.05) and total volume of distribution (26.55±4.80 liter/m², nl 13.10±2.54, P < 0.01). However, the unaltered Kii suggested an extravascular binding impairment comparable to that found in serum. The decreased T₃ production rate (6.34±0.53 μg/d per m², nl 23.47±2.12, P < 0.005) appeared to result from reduced peripheral T₄ to T₃ conversion because of decreased 5′-deiodination rather than from a decreased T₄ availability. This view was supported by the normality of the rT₃ production rate. The normal Kii values for rT₃ indicated a comparable defect in serum and extravascular rT₃ binding. The reduced MCR (25.05±6.03 liter/d per m², nl 59.96±8.56, P < 0.005) and FCR (191.0±41.19%, nl 628.0±199.0, P < 0.02) for rT₃ are compatible with an impairment of the rT₃ deiodination rate.These alterations in thyroid hormones indices and kinetic parameters for T₄, T₃, and rT₃ in the low T₄ state of acute nonthyroidal illnesses can be accounted for by: (a) decreased binding of T₄, T₃, and rT₃ to vascular and extravascular sites with a proportionately greater impairment of extravascular T₄ binding, and (b) impaired 5′-deiodination activity affecting both T₄ and rT₃ metabolism.