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Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica.