Plasma thyroid hormone kinetics are altered in iron-deficient rats

Iron deficiency anemia is associated with lower plasma thyroid hormone concentrations in rodents and, in some studies, in humans. The objective of this project was to determine if plasma triiodothyronine (T-3) and thyroxine (T-4) kinetics were affected by iron deficiency. Studies were done at a near-thermoneutral temperature (30 degrees C), and a cool environmental temperature (15 degrees C), to determine plasma T-3 and T-4 kinetics as a function of dietary iron intake and environmental need for the hormones. Weanling male Sprague-Dawley rats were fed either a low Fe diet [iron-deficient group (ID), <5 mu g/g Fe] or a control diet [control group (CN), 35 mu g/g Fe] at each temperature for 7 wk before the tracer kinetic studies. An additional ID group receiving exogenous thyroid hormone replacement was also used at the cooler temperature, For T-4, the disposal rate was >60% lower (89 +/- 6 vs, 256 +/- 53 pmol/h, P < 0.001) in ID rats than in controls at 30 degrees C, and similar to 40% lower (192 +/- 27 vs. 372 +/- 26 pmol/h, P < 0.01) in ID rats at 15 degrees C. Exogenous T-4 replacement in a cohort of ID rats at 15 degrees C normalized the T-4 concentration and the disposal rate. For T-3, the disposal rate was significantly lower in ID rats in a cool environment (92 +/- 11 vs, 129 +/- 11 pmol/h, P < 0.01); thyroxine replacement again normalized the T-3 disposal rate (126 +/- 12 pmol/h). Neither liver nor brown fat thyroxine 5'-deiodinase activities were sufficiently different to explain the lower T-3 disposal rates in iron deficiency. Thus, plasma thyroid hormone kinetics in iron deficiency anemia are corrected by simply providing more thyroxine, This suggests a central regulatory defect as the primary lesion and not peripheral alterations.