A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism.

LT4/placebo treatment resulted in significantly higher free T4 and lower total T3 levels following thyroidectomy, while these changes were not observed in the LT4/LT3 group.

• LT4/placebo resulted in higher free T4 of +0.26 ± 0.15 (p<0.005)
• LT4/placebo resulted in lower total T3 of -18 ± 9.6 ng/dl (p<0.003)
• These significant changes in free T4 and total T3 were not observed in the LT4/LT3 group
• TSH showed no significant differences between groups

The LT4/placebo group had a non-significant increase in body weight, total cholesterol, and LDL cholesterol, while the LT4/LT3 group showed opposite non-significant trends.

• LT4/placebo group: body weight change +1.7 ± 3.8 Kg, total cholesterol +43.1 ± 72.8 mg/dl, LDL cholesterol +32.0 ± 64.4 mg/dl (all non-significant)
• LT4/LT3 group: body weight change -0.6 ± 1.9 Kg, total cholesterol -28.8 ± 49.0 mg/dl, LDL cholesterol -19.0 ± 28.3 mg/dl (all non-significant)
• None of the between-group differences in weight or cholesterol reached statistical significance

Energy expenditure and diastolic function increased in the LT4/LT3 group.

• Energy expenditure increased in the LT4/LT3 group but not in the LT4/placebo group
• Diastolic function also increased in the LT4/LT3 group
• These cardiovascular and metabolic outcomes were assessed in patients who completed at least the 3-month visit, with last measure carried forward

Non-significant improvements in quality of life as measured by ThyPRO-39 were observed in both treatment groups.

• ThyPRO-39 was used as the quality of life measure
• Both the LT4/placebo and LT4/LT3 groups showed non-significant improvements in ThyPRO-39 measures
• No significant between-group differences in quality of life were reported

This was a small feasibility double-blind, placebo-controlled trial enrolling 12 patients with post-surgical hypothyroidism over 24 weeks.

• 12 patients total were analyzed: 10 women and 2 men, age 51 ± 13.8 years
• 7 patients were in the LT4/placebo group and 5 in the LT4/LT3 group
• Study duration was 24 weeks conducted at an academic medical center
• LT3 dose was 5 mcg twice daily; LT4 was adjusted at 6 and 12 weeks with goal of baseline TSH ± 0.5 mcIU/ml
• Registered at ClinicalTrials.gov as NCT05682482

Some patients with hypothyroidism treated with levothyroxine report residual symptoms despite TSH normalization, potentially attributable to loss of endogenous triiodothyronine (T3).

• The rationale for combination therapy is that surgical removal of the thyroid eliminates endogenous T3 production
• LT4 monotherapy may not fully replicate the normal thyroid hormone milieu
• This provides the clinical rationale for investigating LT4/LT3 combination therapy in post-surgical hypothyroidism