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Jacqueline Jonklaas, MD, PhD; Bruce Davidson, MD; Supna Bhagat, MD; Steven J. Soldin, PhD

JAMA. 2008;299(7):769-777.

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 LT₄ 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.

Author Affiliations: Division of Endocrinology (Dr Jonklaas) and Departments of Medicine (Drs Jonklaas and Bhagat) and Otolaryngology-Head and Neck Surgery (Dr Davidson), and Bioanalytic Core Laboratory, General Clinical Research Center (Dr Soldin), Georgetown University Medical Center, Washington, DC; and Department of Laboratory Medicine, Children's National Medical Center, Washington, DC (Dr Soldin). Dr Bhagat is now with the Division of Endocrinology, Eastern Virginia Medical School, Hampton Roads, Virginia.

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