Thyroid abnormalities are common endocrine disorders in the United States, for which thyroid hormones are frequently prescribed. Levothyroxine (L-T4) is often considered the thyroid hormone of choice due to its long half-life, stability, uniform potency, lack of allergenic foreign protein, and relative low cost. Thyroid function tests (TFTs: free and total thyroxine, total triiodothyronine, and thyrotropin) are used to monitor efficacy of L-T4 therapy. Studies have suggested that L-T4 has a 9-hour distribution phase, resulting in a 9% - 55% increase in free and total thyroxine and a 23% to 40% decrease in thyrotropin serum concentrations following L-T4 administration. Although these studies have suggested monitoring therapy based on blood specimens collected prior to the usual daily L- T4 administration, state-of-the-art practice is to assess TFTs post L- T4 administration. Further, it is unclear whether the changes in TSH are due to drug administration or related to normal diurnal variation. This randomized, prospective, open-label, cross-over study, involving a total of 44 patients receiving L-T4 therapy, will evaluate the effects of L-T4 administration time on TFTs. Patients will be randomly assigned to either Group A (7 suppression, 7 replacement and 8 high- dose patients who will receive their usual L-T4 dose prior to serial TFTs) or Group B (7 suppression, 7 replacement and 8 high-dose patients who will receive their usual L-T4 dose after serial blood sampling for determination of TFTs). After a wash-out period of not less than one week, patients will be crossed over to the alternate group. Pharmacokinetic parameters (Cmax. Tmax, Kel, T1/2, AUC, Vd, F) will be compared statistically between groups. Results have not yet been formally analyzed, but suggest that thyrotropin concentrations follow a diurnal pattern in both treatment groups.
