Combination Therapy of LT4+LT3 Not Superior to Monotherapy Among Patients of Primary Hypothyroidism

Several clinical trials addressed the question of whether residual symptoms could be resolved through the use of combination therapy with LT4 and liothyronine (LT3), but evidence of consistent superiority of combination therapy was not obtained. Therefore, Dr Thanh D Hoang and his team conducted a study comparing 3 different forms of thyroid hormone replacement therapy, while also exploring the most symptomatic patients.

In a prospective, randomized, double-blind, crossover study, the researchers included 75 hypothyroid patients and randomized them to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The major outcomes were post-treatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), and the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). They further assessed treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. They performed the analysis with a linear mixed model using the subject as a random factor and the group as a fixed effect.

Key findings of the study:

• Upon analysis, the researchers noted that the serum TSH remained within the reference range across all treatment arms.
• They found no differences in primary and secondary outcomes, except for a minor increase in heart rate caused by DTE.
• They noted that the treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes.
• Upon subgroup analyses of the 1/3 most symptomatic patients on LT4, they found a strong preference for a treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).

The authors concluded, "As a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE."

For further information:

DOI: https://doi.org/10.1210/clinem/dgab478

Keywods:

Levothyroxine, liothyronine, desiccated thyroid extract, Hypothyroidism, Quality of life, LT4+LT3, LT4, LT3, DTE, Thyroid disorder, Journal of Clinical Endocrinology.