Triiodothyronine levels in athyreotic individuals during levothyroxine therapy

JAMA. 2008 Feb 20;299(7):769-77. doi: 10.1001/jama.299.7.769.


Context: Thyroidal production of triiodothyronine (T3) is absent in athyreotic patients, leading to the suggestion that T3 deficiency may be unavoidable during levothyroxine (LT4) therapy. However, trials evaluating therapy with combined LT4 and T3 have failed to demonstrate any consistent advantage of combination therapy.

Objective: To determine whether T3 levels in patients treated with LT4 therapy were truly lower than in the same patients with native thyroid function.

Design, setting, and patients: A prospective study conducted in the General Clinical Research Center, Georgetown University Medical Center, Washington, DC, between January 30, 2004, and June 20, 2007, of 50 euthyroid study participants aged 18 to 65 years who were scheduled for total thyroidectomy for goiter, benign nodular disease, suspected thyroid cancer, or known thyroid cancer. Following thyroidectomy, patients were prescribed LT4. Patients with benign thyroid disease and thyroid cancer were treated to achieve a normal and suppressed serum thyroid-stimulating hormone (TSH) level, respectively. The LT4 dose was adjusted as necessary postoperatively to achieve the desired TSH goal.

Main outcome measure: Thyroxine (tetraiodothyronine [T4]), T3, and TSH levels were measured twice preoperatively and twice postoperatively.

Results: By the end of the study, there were no significant decreases in T3 concentrations in patients receiving LT4 therapy compared with their prethyroidectomy T3 levels (mean, 127.2 ng/dL; 95% confidence interval [CI], 119.5-134.9 ng/dL vs 129.3 ng/dL; 95% CI, 121.9-136.7 ng/dL; P = .64). However, free T4 concentrations were significantly higher in patients treated with LT(4) therapy (mean, 1.41 ng/dL; 95% CI, 1.33-1.49 ng/dL) compared with their native free T4 levels (1.05 ng/dL; 95% CI, 1.00-1.10 ng/dL; P < .001). Serum TSH values of 4.5 mIU/L or less were achieved in 94% of patients by the end of the study. The T3 concentrations were lower in the subgroup of patients whose therapy had not resulted in a TSH level of 4.5 mIU/L or less (P < .001).

Conclusion: In our study, normal T3 levels were achieved with traditional LT4 therapy alone in patients who had undergone near-total or total thyroidectomy, which suggests that T3 administration is not necessary to maintain serum T3 values at their endogenous prethyroidectomy levels.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Hormone Replacement Therapy*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Thyroid Diseases / surgery
  • Thyroid Hormones / blood
  • Thyroidectomy*
  • Thyrotropin / blood
  • Thyroxine / therapeutic use*
  • Triiodothyronine / blood*


  • Thyroid Hormones
  • Triiodothyronine
  • Thyrotropin
  • Thyroxine