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The following is a summary of “A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism,” published in the March 2025 issue of Frontiers in Endocrinology by Phan et al. 

Some individuals with hypothyroidism on Levothyroxine (LT4) continue to experience symptoms despite normalized Thyrotropin (TSH), possibly due to reduced endogenous triiodothyronine (T3). 

Researchers conducted a retrospective study to evaluate the feasibility of LT4 and Liothyronine (LT3) combination therapy vs LT4 with placebo in individuals with post-surgical hypothyroidism. 

They performed a 24-week study at an academic medical center, including individuals requiring total thyroidectomy and replacement therapy. Participants received either LT4 with LT3 5 mcg twice daily or LT4 with placebo twice daily. The LT4 doses were adjusted at 6 and 12 weeks to maintain TSH within ±0.5 mcIU/ml of baseline. Outcomes included changes in body weight, cholesterol, TSH, total T3, and free Tetraiodothyronine (T4). Cardiovascular function, energy expenditure, and QoL (ThyPRO-39) were evaluated in those who completed at least 3 months, using the last recorded value if a visit was missed. 

The results showed that 12 individuals (10 women, 2 men) with a mean age of 51 ± 13.8 years were analyzed (7 in the LT4/placebo group, 5 in the LT4/LT3 group). No significant differences were found in TSH. After thyroidectomy, LT4/placebo led to increased free T4 (+0.26 ± 0.15, P <0.005) and decreased total T3 (-18 ± 9.6 ng/dl, P <0.003), which was not observed in the LT4/LT3 group. The LT4/placebo group had a non-significant rise in body weight (+1.7 ± 3.8 kg), total cholesterol (+43.1 ± 72.8 mg/dl), and low-density lipoprotein (LDL) cholesterol (+32.0 ± 64.4 mg/dl). In contrast, the LT4/LT3 group showed non-significant decreases in body weight (-0.6 ± 1.9 kg), total cholesterol (-28.8 ± 49.0 mg/dl), and LDL cholesterol (-19.0 ± 28.3 mg/dl). Non-significant improvements were noted in ThyPRO-39 scores in both groups, while energy expenditure and diastolic function increased in the LT4/LT3 group. 

Investigators concluded that in post-surgical hypothyroidism, LT4 monotherapy failed to normalize thyroid hormone levels and was associated with weight and cholesterol increases, while LT4/LT3 combination therapy mitigated these effects. 

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1522753/full