Patients with hypothyroidism treated with the three most common pharmacological strategies of levothyroxine (LT4) alone, LT4 in combination with triiodothyronine (T3), or desiccated thyroid extract showed no differences in thyroid symptoms or secondary outcomes in a double-blind randomized 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,” first author Thanh Duc Hoang, DO, an endocrinologist at the Walter Reed National Military Medical Center, in Bethesda, Maryland, said in a press statement.
The findings were presented as part of the virtual ENDO 2021, the Endocrine Society’s annual meeting.
Commenting on the study, Alan P. Farwell, MD, said these new results are a valuable contribution to the understanding of treatment effects. “I think this is an interesting and important study and further studies are needed to clarify the optimal way to treat hypothyroidism,” said Farwell, who is director of Endocrine Clinics at Boston University School of Medicine, Massachusetts.
Importantly, “the findings are different than studies where the patients are aware of what medication they are receiving,” he stressed to Medscape Medical News, underscoring the importance of the double-blind design of the trial.
But Anne Cappola, MD, of the University of Pennsylvania School of Medicine, in Philadelphia, pointed out, “The study was small and unlikely to have the statistical power to detect differences that could have been clinically important.”
Nevertheless, she too agrees the double-blind study design is key: “My experience with patients is [the effects] are affected by patients’ perceptions about their thyroid medication. That is why studies designed so that patients do not know which treatment they are receiving are so important in this area.”
Randomized, Double-Blind Comparison
Prior to the widespread availability of the current gold standard hypothyroidism treatment of LT4, the condition was typically treated with desiccated (animal) thyroid extract. And with many patients continuing to have a preference for this therapeutic approach, it is still commonly used.
Additionally, some patients treated with LT4 alone report greater improvements in symptoms with the addition of T3 — despite studies showing no benefits from the two together — leading to many clinicians commonly trying the combination approach.
To compare the efficacy of the three approaches in a prospective, double-blind cross-over fashion, 75 patients received three therapeutic approaches each for 3 months: desiccated thyroid extract, an LT4/T3 combination, or LT4 alone.
After each 3-month treatment, patients completed a 36-point thyroid symptom questionnaire.
There was no significant differences in symptom relief, the primary outcome, between the three treatments (P = .32).
Overall, 45% of patients indicated they preferred desiccated thyroid as their first choice of treatment, 32% preferred LT4/T3 as their first choice, and 23% preferred LT4 alone.
For the secondary endpoints of weight, general health, depression (assessed using the Beck Depression Inventory), memory (Wechsler Memory Scale), lipids, and thyroid function, again, there were no significant differences between groups in any of the measures.
When Switched to Desiccated Thyroid, Many Felt ‘Much Better‘
A further exploratory analysis revealed that those who experienced symptoms while taking LT4 alone reported greater alleviation of symptoms with the other two treatments.
“As a whole group, there was no significant difference between the three treatment arms,” Hoang explained to Medscape Medical News.
“However, with the subgroup analysis based on the scores of symptom questionnaires, we found that symptomatic patients on LT4 improved while being treated with LT4/T3 or desiccated thyroid,” he said.
Reports of improvements in switching to desiccated thyroid were notable, Hoang added. “Many patients when switched from LT4 to desiccated thyroid extract said they felt much better, [with] more energy, less mental fogginess, a better outlook, less flair of lupus symptoms, easier to lose weight, etc.”
The study also showed more patients with Hashimoto’s disease preferred desiccated thyroid extract and LT4/T3 compared with LT4 alone, however, the differences were not significant.
Treatment Adjustments a Helpful First Step
Farwell noted that his approach when patients are still reporting symptoms despite LT4 treatment is to first try tweaking the dose.
“In my own practice, I prefer to adjust LT4 dosing first, and on occasion add T3, with a goal of getting both hormone levels in the upper half of the normal range,” he said.
“I find that to be a better approach than desiccated thyroid extract. T3 should be taken twice a day due to its half-life,” Farwell noted.
The approach is generally successful, he added.
“Even those that come in asking for desiccated thyroid extract whom I am able to convince to try LT4/T3 end up being happy with their treatment in the end.”
“The key is that you need to spend time discussing the options with patients and come to a consensus as to the therapy that will best resolve their symptoms and that they are most comfortable with,” he concluded.
In response to mounting evidence of different hypothyroidism treatment responses according to various subgroups of patients, experts recently called for the initiation of more thorough clinical trials on the issue of combination therapy, as recently reported by Medscape Medical News.
Hoang has reported being a speaker for Acella Pharmaceuticals. Farwell and Cappola have reported no relevant financial relationships.
ENDO 2021. Abstract P51-6. Presented March 20, 2021.