Influence of thyroidectomy on thyroxine metabolism and turnover rate in rats

Abstract

Little is known about the kinetics and metabolism of thyroid hormones in the hypothyroid state. To investigate these factors, we developed a reliable method for measurement of serum thyroxine (T4), triiodothyronine (T3), reverse-T3 (rT3) and stable isotope-labeled T4 ([13C9]T4), using online solid-phase extraction liquid chromatography–mass spectrometry/mass spectrometry (online SPE LC–MS/MS). We measured supply and turnover rates of T4 in thyroidectomized (Tx) rats using [13C9]T4 as a tracer. In rats, serum T4, T3 and rT3 were decreased but not completely ablated after surgical Tx. Endogenous T4 and T3 levels in Tx rats were maintained at a constant low level throughout the experimental period. [13C9]T4 levels declined with a half-life of ∼1.2 days after it was administered to Tx rats intravenously. These findings strongly suggest that serum T4 levels in Tx rats are maintained by T4 supplied by extra-thyroidal tissues (e.g. secretion of extra-thyroidal storage, enhancement of enterohepatic recirculation, and production in extra-thyroidal tissues). Moreover, the turnover rate of T4 in Tx rats was approximately twofold lower than in controls. This finding suggests that degradation of serum T4 is repressed by Tx. In conclusion, serum T4 is maintained at a constant low level by T4 supply from extra-thyroidal tissues and repression of T4 degradation in Tx rats. The powerful online SPE LC–MS/MS tool can be used to investigate thyroid hormones kinetics and metabolism, and thus has the potential to be used as a diagnostic tool and to investigate the pathogenesis of thyroid disease.