title: 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 (T(4)), triiodothyronine (T(3)), reverse-T(3) (rT(3)) and stable isotope-labeled T(4) ([(13)C(9)]T(4)), using online solid-phase extraction liquid chromatography-mass spectrometry/mass spectrometry (online SPE LC-MS/MS). We measured supply and turnover rates of T(4) in thyroidectomized (Tx) rats using [(13)C(9)]T(4) as a tracer. In rats, serum T(4), T(3) and rT(3) were decreased but not completely ablated after surgical Tx. Endogenous T(4) and T(3) levels in Tx rats were maintained at a constant low level throughout the experimental period. [(13)C(9)]T(4) levels declined with a half-life of ∼1.2 days after it was administered to Tx rats intravenously. These findings strongly suggest that serum T(4) levels in Tx rats are maintained by T(4) 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 T(4) in Tx rats was approximately twofold lower than in controls. This finding suggests that degradation of serum T(4) is repressed by Tx. In conclusion, serum T(4) is maintained at a constant low level by T(4) supply from extra-thyroidal tissues and repression of T(4) 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.
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd, 5-36-1, Shimosakunobe, Kawasaki 213-8522, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nagao
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imazu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kenjo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Minato
mesh_terms: D000818:Animals; D057205:Automation, Laboratory; D002247:Carbon Isotopes; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D052617:Solid Phase Microextraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013961:Thyroid Gland / Q000502:physiology / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
chemical_list: D002247:Carbon Isotopes; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013974:Thyroxine