The Production and Metabolism of 3,5,3′-Triiodothyronine and 3,3′,5′-Triiodothyronine in Normal and Fasting Subjects*

Abstract

The deiodinative pathways of T₄ and the production of T₃ and rT₃ were compared in two groups of normal volunteers on physiological T₄ replacement. One group was given a normal diet and the second group was fasted up to 15 days. After 1 week of fasting, the mean serum T₃ level fell from 140 to 93 ng/dl, and the mean serum rT₃ level rose from 51 to 106 ng/dl. No significant change occurred in the group mean serum concentration of TSH or total or free T₄. These changes were most marked during the fifth to seventh day of fasting, but recovered partly toward the baseline values during the second week of fasting. The ratio of mean serum T₃ to mean serum rT₃ was 2.8 before fasting. It diminished to 0.9 after 1 week of fasting and increased to 1.5 after 2 weeks of fasting. In seven control subjects, the MCRs of T₄, T₃, and rT₃ were 1.27 ± 0.24, 24.0 ± 3.6, and 105 ± 13 liters/day · 70 kg, respectively (mean ± sd). The disposal rates of T₄, T₃, and rT₃ were 140 ± 16, 41 ± 5, and 49 ± 12 μg/day·70 kg, respectively. In seven fasting subjects, the MCRs of T₄, T₃, and rT₃ were 0.95 ± 0.17 (P < 0.01), 19.3 ± 3.9 (P < 0.05), and 55 ± 15 liters/day ·70 kg (P < 0.001), whereas the disposal rates of T₄, T₃( and rT₃ were 113 ± 14 (P < 0.005), 17 ± 4 (P < 0.001), and 58 ± 9 μg/day·70 kg (P < 0.2), respectively. The clearance of rT₃ was reduced 52%, and the T₃ disposal rate was reduced to 41% in the fasting subjects. The mean rT₃ disposal rate remained unchanged, but the rT₃ disposal to T₄ disposal ratio rose from 0.35 to 0.51 during fasting. The T₄ to T₃ conversion rate was reduced to 50%, and the T₄ to rT₃ conversion rate was increased to 146% in the fasting group as compared to the control group. The proportion of T₄ metabolized by deiodination remained unchanged (77% in the control group and 76% in the fasting group). The results suggest that in subjects of good health, severe caloric deprivation impaired iodothyronine deiodiation in general, and in particular the deiodination at 5′ position, thereby reducing both T₃ production and rT₃ clearance. Significant shunting of T₄ metabolism away from T₃ production into rT₃ production was noted. Fasting did not alter the proportion of T₄ undergoing metabolism via the deiodinative pathways compared to the nondeiodinative pathways.