Amiodarone alters thyroxine transfer and distribution in humans.

Previous studies indicate that increased serum total and free T4 levels may be secondary to a proportionally greater decrease in serum T4 clearance rates than in production rates after short-term amiodarone administration, to increased T4 production rates as well as reduced serum clearance rates in selective hyperthyroxinemia without overt hyperthyroidism following chronic amiodarone administration, and to a relatively greater increase in T4 production rates than in clearance rates in classical hyperthyroidism. To further evaluate amiodarone-induced alterations of T4 metabolism, serum T4 transfer and distribution were evaluated by compartmental analysis of T4 kinetic studies from eight normal subjects receiving short-term amiodarone or an equivalent amount of iodide, five patients with selective hyperthyroxinemia induced by chronic amiodarone therapy (n = 4) or ioxithalamic acid (n = 1), and five with classical hyperthyroidism. The model consisted of rapidly and slowly equilibrating pools exchanging with serum, with all losses occurring from the tissue pools. Short-term amiodarone administration reduced the fractional T4 transfer rates between serum and the rapidly equilibrating pool to 82% of baseline. In selective hyperthyroxinemia the fractional rates of T4 transfer between serum and both extravascular pools were increased sixfold, whereas minimal alterations were present in the hyperthyroid group. The serum equivalent volume of T4 distribution in the slow pool was significantly reduced following short-term amiodarone, whereas serum and rapid pool volumes were reduced in selective hyperthyroxinemia and slow pool volume was increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroxine transfer and distribution in critical nonthyroidal illnesses, chronic renal failure, and chronic ethanol abuse.

Serum T4 kinetic studies were performed in euthyroid patients with acute critical illnesses, chronic renal failure, or ethanol abuse without overt hepatocellular damage and in healthy euthyroid subjects with normal or altered serum T4 binding to determine the relative effects of altered serum T4 binding and extravascular disturbances on T4 transfer and distribution in nonthyroidal illnesses. A three-pool model with rapidly and slowly equilibrating pools exchanging with serum was used to evaluate the potential sites of alterations. Healthy euthyroid subjects with low serum T4-binding globulin levels had increased serum percent free fraction of T4 (%FFT4) and fractional T4 transfer rates (FTR) from serum to both extravascular pools, while those with high serum T4-binding capacity had decreased %FFT4 and FTR from serum to the rapid pool and increased T4 binding in the slow pool. Critically ill patients had significantly reduced serum total T4 (TT4) with increased %FFT4 but decreased FTR from serum to both extravascular pools and reduced T4 binding in the slow pool. Patients with ethanol abuse had normal serum TT4 and %FFT4 but significantly increased FTR from serum to the rapid pool and increased binding in both extravascular pools. Chronic renal failure patients had no alterations in any of these values. The T4 FTR from serum to both extravascular pools were directly related to the serum %FFT4 in healthy subjects and inversely related in the patients. Further, the FTR from the rapid pool to serum were inversely related to rapid pool binding in healthy subjects but not in the patients, while the FTR from the slow pool to serum were unrelated to slow pool binding in both groups. These findings indicate that in patients with nonthyroidal illnesses the transfer of T4 between serum and the extravascular pools is not primarily a reflection of T4 binding to serum binding proteins or extravascular sites. Further, alterations in slow pool binding may be affected by changes in T4 binding to serum binding proteins, which are known to be present in the interstitial fluid of these tissues. Finally, the type and magnitude of the alterations in T4 transfer and distribution in patients with nonthyroidal illnesses appear to differ for rapidly and slowly equilibrating tissues and may be related to the etiology and/or severity of the nonthyroidal disorder.

Acute hemodynamic effects of levothyroxine loading in critically ill hypothyroid patients.

To evaluate the acute cardiovascular effects of high-dose levothyroxine sodium therapy, the hemodynamic findings in eight critically ill hypothyroid patients treated with high-dose levothyroxine were compared with those in two critically ill hypothyroid and nine critically ill euthyroid patients not receiving this therapy. The initial cardiac index was significantly lower in the hypothyroid group; all other hemodynamic values were similar to those of the euthyroid patients. Following levothyroxine loading, the free thyroxine index increased to normal while the free triiodothyronine index was unchanged; all patients had a significant rise in cardiac index but no consistent changes in the other hemodynamic values. Cardiac index correlated positively with heart rate (three patients) and/or stroke volume index (six patients). Increases in stroke volume index correlated with decreases in systemic vascular resistance (five patients), but not with increases in pulmonary artery wedge pressure. No consistent patterns of hemodynamic changes were observed in the untreated hypothyroid or the euthyroid patients.