Metabolic Contributions to Subclinical Hypothyroidism: Does Dysregulation of Thyroid Hormone Receptor Affinity Play a Role?

Abstract

Symptoms consistent with a syndrome of subclinical hypothyroidism are often reported by patients undergoing weight related assessment for a variety of metabolic conditions and disorders including obesity and metabolic syndrome. To determine the potential for subclinical thyroidal actions as a contributing factor for hormonal regulation of energy balance  and the development of obesity and metabolic syndrome, studies of resting and catecholamine stimulated metabolism, thyroid hormone half-life, hormone bind characteristics and weight gain, groups of lean and obese congenic LA/Ntul//-cp rats were offered stock or high energy diets and parameters of thyroid hormone action determined. The obese phenotype demonstrated impaired thermic responses to diet and environment and cold induced thermoregulation, in association with decreases in plasma T3 but not T4 concentrations. The plasma half-life of T4 was 50% longer in obese than in lean littemates, while the half-life of T3 was similar in both phenotypes. Measures of nuclear thyroid hormone receptor density were similar in both phenotypes, but receptor affinity for T3 was diminished in the obese phenotype, consistent with dysregulation of parameters of thyroidal actions as contributing factors for subclinical hypothyroidism in the obese phenotype of this strain.