A Feasibility Double-Blind Trial of Levothyroxine vs. Levothyroxine-Liothyronine in Postsurgical Hypothyroidism

Giao Q Phan ¹ Sahzene Yavuz ² Angeliki Maria Stamatouli ³ Ritu Madan ³ Shanshan Chen ³ Amelia C Grover ³ Naris Nilubol ⁴ Pablo Bedoya ⁵ Cory Trankle ³ Roshanak Markley ³ Antonio Abbate ⁶ Francesco S Celi ^1*

• ¹ UCONN Health, Farmington, Maryland, United States
• ² Guthrie Robert Packer Hospital, Sayre, Pennsylvania, United States
• ³ Virginia Commonwealth University, Richmond, Virginia, United States
• ⁴ National Institutes of Health (NIH), Bethesda, Maryland, United States
• ⁵ Virginia Diabetes & Endocrinology, Richmond, United States
• ⁶ University of Virginia, Charlottesville, Virginia, United States

Context: Despite normalization of Thyrotropin (TSH), some patients with hypothyroidism treated with Levothyroxine (LT4) report residual symptoms which may be attributable to loss of endogenous triiodothyronine (T3).Objective: Feasibility trial LT4/liothyronine (LT3) combination vs. LT4/placebo in post-surgical hypothyroidism.Design: Double-blind, placebo-controlled, 24-week study.Patients: Individuals with indications for total thyroidectomy and replacement therapy.Interventions: LT4/LT3 5 mcg (twice daily) vs. LT4/placebo (twice daily). LT4 was adjusted at 6-and 12weeks with the goal of baseline TSH±0.5 mcIU/ml.Changes in body weight, cholesterol, TSH, total T3, free tetraiodothyronine (T4). Cardiovascular function, energy expenditure, and quality of life (ThyPRO-39) were assessed in patients who completed at least the 3-month visit, last measure carried-forward.Results: Twelve patients (10 women and 2 men), age 51±13.8 years (7 LT4/placebo, 5 LT4/LT3), were analyzed. No significant differences were observed in TSH. Following thyroidectomy, LT4/placebo resulted in higher free T4 +0.26±0.15 p<0.005 and lower total T3 -18±9.6 ng/dl p<0.003, respectively, not observed in the LT4/LT3 group. The LT4/placebo group had a non-significant increase in body weight, +1.7±3.8 Kg, total-and LDL-cholesterol +43.1±72.8 and +32.0±64.4 mg/dl. Conversely the LT4/LT3 group changes were -0.6±1.9 Kg, -28.8±49.0 and -19.0±28.3 mg/dl, respectively, all non-significant. Non-significant improvement were observed in ThyPRO-39 measures in both groups, while energy expenditure, and diastolic function increased in the LT4/LT3 group.In this group of patients with post-surgical hypothyroidism LT4 replacement alone does not normalize free T4 and total T3 levels and is associated with non-significant increase in weight and cholesterol. LT4/LT3 combination therapy appears to prevent these changes.