Patterns of 3,3′,5′-Triiodothyronine Monodeiodination in Hypothyroidism and Nonthyroid Illnesses*

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Abstract
Available evidence suggests that outer ring monodeiodination of T4 is reduced in nonthyroidal illnesses (NTI), whereas it is normal or increased in hypothyroid patients. To determine whether a similar abnormality also occurs in rT3 metabolism, we have studied serum concentration of 3,3′-diiodothyronine (T2) after oral administration of 300 µg rT3 to 13 normal, 7 hypothyroid, and 12 NTI individuals. Also, we studied serum concentrations of 3′,5′-T2 after rT3 administration in order to examine the effect of hypothyroidism and NTI on inner ring monodeiodination of rT3. The mean increments above baseline serum concentrations of rT3 and 3′,5′-T2 did not differ significantly in normal, NTI, and hypothyroid groups at anytime during 4 h after rT3 administration. However, increments above baseline serum 3,3′-T2 concentrations 1 and 2 h after rT3 administration were significantly lower (P < 0.05) in the NTI group (mean ± SE, 0.7 and 0.9 ± 0.7 ng/dl, respectively) than in the normal group (2.7 ± 0.7 and 3.8 ± 0.9 ng/dl, respectively) or the hypothyroid patients (6.7 ± 2.7 and 8.5 ± 2.9 ng/dl, respectively); the values in hypothyroid patients did not differ significantly from those in normal subjects. The changes above baseline in serum rT3, 3,3′- T2, and 3′,5′-T2 levels after rT3 administration also were examined by comparison of the areas under the serum concentration curves (AUSCC) or their ratios. The AUSCC for rT3 and 3′,5′-T2 or the 3′,5′-T2 to rT3 ratios were not significantly different in the three groups. However, the mean AUSCC for 3,3′-T2 and the 3,3′-T2 to rT3 ratio (xlOOO) for NTI patients (2.8 ± 5.9 and 2.3 ±1.0 ng/dl-hr, respectively) were significantly lower than those in normal subjects (10 ± 2.3 and 8.9 ±1.8 ng/dl-hr, respectively) and hypothyroid patients (21 ± 7.5 and 21 ± 6.2 ng/dl-hr, respectively; P < 0.01). The mean AUSCC of 3,3′-T2 in hypothyroid patients did not differ significantly from that in normal subjects, but their mean 3,3′-T2 to rT3 AUSCC ratio was significantly (P < 0.05) higher than normal. Our data suggest that monodeiodination of rT3 in the outer ring (to 3,3′-T2) is reduced in NTI and normal subjects or increased in hypothyroid patients, while that in the inner ring (to 3′,5′-T2) is normal in both conditions.

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