title: A Double-Blind Placebo-Controlled Trial of Liquid Thyroxine Ingested at Breakfast: Results of the TICO Study.
abstract: BACKGROUND
  Levothyroxine (LT4) is the recommended treatment for millions of hypothyroid patients. Current guidelines recommend that LT4 tablets be taken in a fasting state, but inability to adhere to this often leads to poor therapy compliance.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, crossover trial was conducted in previously untreated hypothyroid patients randomly assigned to receive an oral solution of LT4 either at least 30 minutes before breakfast or directly at breakfast time. Each patient completed two six-week treatment periods, with different timing of active LT4 administration: placebo before breakfast and active LT4 at breakfast, or vice versa. At the end of each period, thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were measured. The primary endpoint was to verify any difference in serum TSH levels whether consuming liquid LT4 at breakfast or 30 minutes prior to breakfast.
  
  
  RESULTS
  A total of 77 patients (64 females; median age 45.4 ± 3.7 years) completed the study. No statistically significant differences in serum TSH, fT4, or fT3 levels were observed whether LT4 was taken at breakfast or 30 minutes before, in a fasting state. No significant effect from the sequence of regimens, breakfast composition, and/or concomitantly administered drugs was observed on the dose of LT4 administered, or on the post-treatment serum TSH values.
  
  
  CONCLUSIONS
  The TICO study suggests that a liquid LT4 formulation can be ingested directly at breakfast, thus potentially improving therapeutic compliance. This observation is of considerable clinical relevance, since non-adherence to LT4 therapy requirements is more likely to cause variability in serum TSH concentrations.
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Carlo
authors.initials: C
authors.lastname: Cappelli
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pirola
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Linda
authors.initials: L
authors.lastname: Daffini
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Annamaria
authors.initials: A
authors.lastname: Formenti
authors.affiliation: 2 Department of Molecular and Translational Medicine, University of Brescia , Brescia, Italy .
authors.forename: Carmelo
authors.initials: C
authors.lastname: Iacobello
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cristiano
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Elena
authors.initials: E
authors.lastname: Gandossi
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Enrico
authors.initials: E
authors.lastname: Agabiti Rosei
authors.affiliation: 1 Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia , Brescia, Italy .
authors.forename: Maurizio
authors.initials: M
authors.lastname: Castellano
mesh_terms: D000328:Adult; D062408:Breakfast; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005215:Fasting; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000097:blood
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine