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.
Elaine M. Kaptein, William J. Robinson, Deborah A. Grieb, John T. Nicoloff