title: Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters.
abstract: Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters.
  
  
  
  Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed.
  
  
  
  Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period.
  
  
  
  Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum TSH to the values seen during levothyroxine therapy. There were significant excursions in serum total and free T3 concentrations with once-daily therapy. Trials of combination therapy are likely to be associated with similar excursions, albeit of a lesser magnitude. Only the physical component score of the SF36 questionnaire and hyperthyroid symptoms changed significantly with conversion to liothyronine monotherapy. Sustained release preparations with stable serum T3 profiles may have entirely different outcomes.
authors.affiliation: 1 Division of Endocrinology, Georgetown University Medical Center , Washington, DC.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Jonklaas
authors.affiliation: 2 Endocrine Section, MedStar Washington Hospital Center , Washington, DC.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Burman
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D050031:Hashimoto Disease / Q000097:blood / Q000188:drug therapy*; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine