Different effects of amiodarone on transport of T4 and T3 into the perfused rat liver

Abstract

Uptake and metabolism of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were studied in isolated perfused livers of control and amiodarone-treated rats (40 mg.kg body wt-1.day-1, 22 days). With the use of this perfusion system and a two-pool model describing thyroid hormone kinetics, total uptake was evaluated by the half-time (t1/2) of the fast component of the biphasic thyroid hormone disappearance from the medium and by the fractional influx rate constant (k21). Metabolism was assessed by the t1/2 of the slow component, by determination of breakdown products in medium and bile, and by thyroid hormone disposal according to the two-pool model. Disposal was corrected for differences in mass transfer into the metabolizing pool. In amiodarone-treated rats, both uptake and metabolism of T4 were decreased. Furthermore, it was shown that only transport into the metabolizing liver compartment and not uptake into the nonmetabolizing liver compartment was decreased. Both uptake and total metabolism of T3 were unaffected by amiodarone. The results showed that the different transport systems for T4 and T3 described in isolated rat hepatocytes may also be operative in the intact rat liver. Furthermore, it can be concluded that the low-T3 syndrome, caused by treatment with amiodarone, may be due to both impaired transport and impaired 5'-deiodination.

Different Regulation of Thyroid Hormone Transport in Liver and Pituitary: Its Possible Role in the Maintenance of Low T3 Production during Nonthyroidal Illness and Fasting in Man

“…The latter is based on (i) the different kinetics of their mutual inhibition of transport in hepatocytes in vitro, as well as (ii) a different sensitivity of T3 and T4 transport in hepatocytes to a decrease in cellular ATP (34,35), (iii) a much larger effect of fasting on T4 transport than on T3 transport in vivo (7), and (iv) the absence of effects of amiodarone administration on T3 transport in perfused liver as compared to a significant reduction of T4 transport (58). The idea that the thyroid hormone carrier proteins in liver and pituitary are different is schematically depicted in Figure 4.…”

“…Amiodarone Prolonged administration of amiodarone for the treatment of cardiac arrhythmias may, among others, result in a low serum T3 concentration (2). In perfused livers from rats that had been treated with amiodarone for 22 days, uptake and metabolism of T4 were largely decreased, whereas T3 uptake and metabolism were unaffected (58).…”

Fatores Interferentes na Interpretação de Dosagens Laboratoriais no Diagnóstico de Hiper e Hipotireoidismo

“…Os níveis basais e estimulados do TSH podem estar aumentados. Além deste efeito, a amiodarona reduz a entrada do hormônio tireoideano nos tecidos (38), pode reduzir a ligação dos hormônios tireoideanos ao seu receptor (39) e antagonizar a ação hormonal a nível celular (40). A bradicardia observada no uso da droga pode sugerir hipotireoidismo (41).…”

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level

“…The subsequent decreased availability of the substrate T4 in the liver cells results in a diminished 5'-deiodination of T4, which results in a decreased production of triiodothyronine (T3). 2 Amiodarone thus appears to induce a hypothyroid-like condition in extrathyroidal tissues. The antiarrhythmic effect of amiodarone is related to a lengthening of the cardiac action potential, quite similar to what is observed in hypothyroid patients.…”