Trial Information

Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone

In human adults thyroid hormone action plays a critical role in the modulation of metabolism
and the function of virtually all organ/systems. The specificity of the hormonal action is
ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with
the receptors' isoforms and the co-activators and co-repressors specific for the various
cells target of the hormonal action. Circulating and tissue levels of T3 are the result of
the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the
peripheral conversion of T4 into T3, and the degradation of these hormones. This complex
system has only been partially studied in humans and very little is known regarding the
kinetics of T3, and in particular on the correlation between circulating levels of T3 and
end-organ target tissue thyroid hormone action. The aim of this protocol is to characterize
the pharmacokinetics of T3 and its biological effects at various concentrations in a cohort
of thyroidectomized patients undergoing thyroid hormone replacement therapy withdrawal for
the management of thyroid cancer.

Fifteen patients with a clinical indication for thyroid hormone withdrawal in preparation
for 131I therapy or 123I diagnostic scan for follow-up and management of differentiated
thyroid cancer will be recruited for this study. After enrollment in the study, the
patients' baseline characteristics will be determined during an outpatient visit while
receiving levothyroxine (L-T4) therapy. The L-T4 therapy then will be suspended and
substituted with an equivalent thrice daily liothyronine (L-T3) therapy for one month.
Patients will be admitted to the NIH Clinical Center on the day prior to withdrawal of the
T3 therapy until the diagnostic scan or the administration of radioactive iodine. During the
hospitalization for this research protocol, which is expected to last eleven days, the
following studies will be performed: serial blood sampling for circulating thyroid hormones
to obtain pharmacokinetic parameters of L-T3, lipids, glucose and insulin, resting energy
expenditure, echocardiogram, skeletal muscle strength measurement, cardiac, hepatic and
skeletal muscles MRI, and quality of life and well-being questionnaires. The pharmacokinetic
parameters of L-T3 will also be assessed with the first dose after the diagnostic scan or
the administration of radioactive iodine. The results obtained from this study will help in
understanding the effects of thyroid hormone on metabolism, and may lead to important
information on how to optimize the duration of the thyroid hormone therapy withdrawal for
the treatment of thyroid cancer.