Plasma Thyroid Hormone Kinetics Are Altered in Iron-Deficient Rats

Abstract

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 (T3) and thyroxine (T4) 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 T3 and T4 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 microg/g Fe] or a control diet [control group (CN), 35 microg/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 T4, 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 approximately 40% lower (192 +/- 27 vs. 372 +/- 26 pmol/h, P < 0.01) in ID rats at 15 degrees C. Exogenous T4 replacement in a cohort of ID rats at 15 degrees C normalized the T4 concentration and the disposal rate. For T3, 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 T3 disposal rate (126 +/- 12 pmol/h). Neither liver nor brown fat thyroxine 5'-deiodinase activities were sufficiently different to explain the lower T3 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.

Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered?

“…It then could be speculated that the lower TPO activity causes the increased prevalence of TAI in order to try to preserve its function, but that cannot be proven with the current study design. TPO is a heme-dependent protein and when its activity is lower due to ID, the iodine incorporation into thyroglobulin (Tg) and the coupling of iodotyrosines to form thyroid hormones is impaired, leading to lower FT 4 production and higher serum TSH levels (17,18,19). In our analysis, we also showed that SCH is an independent and significant risk factor for the development of TAI.…”

“…Potential mechanisms have already been discussed above in relation to a lower TPO activity. Furthermore, it has been shown that in case of ID, the control of the CNS can be altered, the binding of T 3 to hepatic nuclear receptors changed, oxygen transport altered, and finally the conversion from T 4 to T 3 can be impaired (3,17,18,19).…”

Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial

“…Fe deficiency may influence iodine and thyroid metabolism in several ways. In animal studies, Fedeficiency anemia decreases circulating concentrations of T 3 and T 4 by 20 -40% (7,8). Fe-deficiency anemia also reduces activity of hepatic thyroxine-5-deiodinase, and thereby impairs peripheral conversion and activation of T 4 to T 3 (8).…”

“…Fe-deficiency anemia may also modify nuclear T 3 binding (9). The effects of Fe deficiency on the thyrotropin releasing hormone (TRH) -TSH axis are equivocal: although Fe-deficiency anemia appears to blunt the TSH response to TRH (8), some studies have found an increase in circulating TSH concentrations in Fe-deficiency anemia (10), while others have reported no change or a decrease in TSH (7,8). In human studies, compared with healthy controls, Fe-deficient adults have lower circulating T 4 and T 3 levels and may have higher TSH concentrations (10,32).…”

“…In rats, Fe-deficiency anemia sharply reduces TPO activity and decreases plasma thyroxine (T 4 ) and triiodothyronine (T 3 ) levels (7). Fe-deficiency anemia may also alter central nervous system control of thyroid metabolism (8), modify nuclear T 3 binding (9), reduce peripheral conversion of T 4 to T 3 (8) and increase circulating thyrotropin (TSH) (8,10). In goitrous children, the therapeutic response to oral iodized oil is impaired in children with Fe-deficiency anemia compared with Fe-sufficient children (11).…”