Liothyronine use in a 17 year observational population-based study - the tears study

Clin Endocrinol (Oxf). 2016 Dec;85(6):918-925. doi: 10.1111/cen.13052. Epub 2016 Mar 21.


Objective: To look at adverse outcomes for patients on liothyronine compared to l-thyroxine. Some trials have examined the relative merits of liothyronine but none have looked at adverse outcomes in large numbers.

Study design: An observational study of all patients prescribed thyroid hormone replacement in Tayside Scotland (population 400 000) from 1997 to 2014.

Patients: A study group of patients having ever used liothyronine (n = 400) was compared to those who had only used l-thyroxine (n = 33 955). All patients were followed up until end-point, death or leaving Tayside.

Measurements: Mortality rates and admissions with cardiovascular disease, atrial fibrillation, fractures, breast cancer and mental diseases were compared. Incident use of bisphosphonates, statins, antidepressants and antipsychotics was compared.

Results: Compared to patients only taking l-thyroxine, those using liothyronine had no increased risk of cardiovascular disease [hazard ratio (HR) 1·04; 95% CI 0·70-1·54], atrial fibrillation (HR 0·91: 0·47-1·75), or fractures (HR 0·79: 0·49-1·27) after adjusting for age. There was no difference in the number of prescriptions for bisphosphonates or statins. There was an increased risk of new prescriptions for antipsychotic medication (HR 2·26: 1·64-3·11 P < 0·0001) which was proportional to the number of liothyronine prescriptions. There was a non-significant trend towards an increase in breast cancer and new use of antidepressant medications. During follow-up, median TSH was higher for patients on l-thyroxine alone (2·08 vs 1·07 mU/L; P < 0·001).

Conclusion: For patients taking long-term liothyronine we did not identify any additional risk of atrial fibrillation, cardiovascular disease or fractures. There was an increased incident use of antipsychotic medication during follow-up.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Antipsychotic Agents / therapeutic use
  • Atrial Fibrillation / chemically induced
  • Cardiovascular Diseases / chemically induced
  • Cohort Studies
  • Fractures, Bone / chemically induced
  • Hormone Replacement Therapy
  • Humans
  • Middle Aged
  • Retrospective Studies
  • Thyroxine / therapeutic use
  • Triiodothyronine / adverse effects
  • Triiodothyronine / therapeutic use*


  • Antipsychotic Agents
  • Triiodothyronine
  • Thyroxine