Thyroid Combination Therapy Preferred Over Levothyroxine for Some Hypothyroidism Patients

Thanh D. Hoang, DO

Results of a new randomized, crossover trial from ENDO 2021 suggest a combination therapy was as effective as levothyroxine for treatment of hypothyroidism, without some of the negative effects sometimes associated with levothyroxine.

A 3-arm trial comparing levothyroxine (LT4) monotherapy, desiccated thyroid extract (DTE), and levothyroxine/liothyronine (LT4/T3) combination therapy in patients with hypothyroidism, results indicate there were no significant differences in thyroid function tests or secondary outcomes based on treatment received during the study.

"There are now proven good treatment options for the more than one in 10 patients with hypothyroidism who continue to experience symptoms of fatigue, mental fogginess, weight gain and other symptoms despite taking levothyroxine," said the study's principal investigator, Thanh D. Hoang, DO, a staff endocrinologist at Walter Reed National Military Medical Center, in a statement.

Despite being widely accepted as the standard of care for most patients with hypothyroidism, some patients still report increased incidence of fatigue, mental fogginess, and weight gain with use of levothyroxine. After performing a previous study that found nearly half of the patients examined preferred use of DTE over levothyroxine, investigators designed the current study to further evaluate use of levothyroxine in hypothyroid patients based on genotypic differences of deiodinase type 2.

Overall, 75 subjects completed the 3-arm study, which compared DTE, LT4/T3 combination therapy, and levothyroxine alone. The study used a prospective, randomized, double-blind, crossover design and patients included in the study underwent allocation to 1 of the 3 study arms for 12 weeks.

The primary outcome of interest for the study was a post-treatment score on a 36-point thyroid symptom questionnaire. Secondary outcomes of interest included weight, general health questionnaire, the Beck depression inventory, Wechsler Memory testing, lipid panels, and thyroid function tests.

Upon analysis, investigators found no significant differences between the study arms on the thyroid symptom questionnaire. Additionally, no significant between-group differences were observed among secondary outcomes.

In subgroup assessments, investigators found auditory memory index and visual working memory index were greater among patients in a group defined by presence Hashimoto’s disease than those without Hashimoto’s disease. Investigators pointed out no relationship between presence of Hashimoto's disease based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism.

Further analysis indicated there was no significant differences in primary or secondary outcomes based on various genotypes of deiodinase 2. Investigators also noted there was no relationship between presence of Hashimoto’s or non-Hashimoto’s based on genotypes or likelihood of carrying Thr92AlaD2 polymorphism.

Despite there being no statistically significant preference for any treatment, investigators also highlighted there were numerically more patients with Hashimoto’s preferred DTE and LT4/T3 combination therapy than levothyroxine monotherapy.

This study, “Desiccated Thyroid Extract Versus Synthetic LT4/T3 Combination Versus LT4 Monotherapy in the Treatment of Primary Hypothyroidism With Special Attention to the Thr92AlaD2 Polymorphism,” was presented virtually as part of ENDO 2021.