title: Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients.
abstract: BACKGROUND
  Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.
  
  
  OBJECTIVE
  To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Academic hospital.
  
  
  METHODS
  1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.
  
  
  METHODS
  TSH, FT4 and FT3 concentrations by immunoassays.
  
  
  RESULTS
  FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.
  
  
  CONCLUSIONS
  Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.
authors.affiliation: Endocrine Unit, Department of Clinical and Molecular Biomedicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy. damiano.gullo@poste.it
authors.forename: Damiano
authors.initials: D
authors.lastname: Gullo
authors.forename: Adele
authors.initials: A
authors.lastname: Latina
authors.forename: Francesco
authors.initials: F
authors.lastname: Frasca
authors.forename: Rosario
authors.initials: R
authors.lastname: Le Moli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pellegriti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vigneri
mesh_terms: D016022:Case-Control Studies; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D012189:Retrospective Studies; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013963:Thyroid Hormones; D013972:Thyrotropin; D013974:Thyroxine