Major Research Findings

The thyroid gland secretes both thyroxine (T4) and triiodothyronine (T3), but patients with hypothyroidism are usually treated with thyroxine alone. The physiological importance of thyroid secretion of T3 is unknown. 1 compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine in 33 patients with hypothyroidism. After treatment with thyroxine plus triiodothyronine, patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations than after thyroxine alone, while serum thyrotropin concentrations were similar after both treatments. Six out of 17 scores on tests of cognitive performance and assessments of mood were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, ten out of fifteen visual-analogue scales used to indicate mood and physical status showed significantly better results after treatment with thyroxine plus triiodothyronine. Pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. The study concluded that partial substitution of triiodothyronine for thyroxine in patients with hypothyroidism may improve mood and neuropsychological function, suggesting a specific effect of triiodothyronine normally secreted by the thyroid gland.

A nested sub-study of the TRUST trial, 6 , assessed the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with subclinical hypothyroidism (SHypo). The study found no effect of levothyroxine on bone health in older adults with SHypo over a one-year period.

A pilot study showed that levothyroxine intake at bedtime significantly decreased thyrotropin levels and increased free thyroxine and total triiodothyronine levels. 2 However, no large randomized trial investigating the best time of levothyroxine intake, including quality-of-life evaluation, has been performed.

A single-blind randomized controlled trial, 5 , evaluated the effect of short-term metformin therapy associated with levothyroxine dose decrement on TSH and thyroid hormone levels in non-diabetic patients with differentiated thyroid cancer (DTC). The study found that adding 500 mg of metformin to the drug regimen was not useful to compensate for a 33% reduction in levothyroxine dose in patients with DTC.

7 highlighted that hypothyroidism is a common endocrine disease associated with metabolic diseases, particularly in old age, and long-term treatment with levothyroxine causes many side effects for patients. Herbal medicine can regulate thyroid hormones and prevent side effects.

Previous combination L-T(4)/liothyronine (L-T(3)) therapy trials focused on quality-of-life endpoints, but limited information is available on the effects on other measures of thyroid hormone action. 3 This study investigated the metabolic effects of liothyronine therapy in hypothyroidism.

The use of L-T4 (levothyroxine) in the treatment of primary hypothyroidism causes oxidative stress (OS) and daily discomfort. 4 This study evaluated the activity of some physiological modulators in reducing the side effects of levothyroxine. Results showed that the use of a formula containing OPA with other PMs may limit the incidence of side effects that occur during the initial phase of L-T4 treatment in hypothyroidism.

Benefits and Risks

Benefits Summary

Partial substitution of triiodothyronine for thyroxine in patients with hypothyroidism may improve mood and neuropsychological function. 1

Risks Summary

Levothyroxine has no effect on bone health in older adults with subclinical hypothyroidism over a one-year period. 6

Comparison of Studies

Commonalities of Studies

All of these studies provide valuable information on hypothyroidism and its treatment. These studies are helpful in optimizing treatment methods for hypothyroidism and in understanding the various symptoms associated with this disease. These studies serve as a foundation for further research on hypothyroidism.

Differences in Studies

These studies differ in several aspects, including the patient population studied, study design, outcomes assessed, and results. For example, some studies focus on the effects of combining thyroxine and triiodothyronine, while others examine the impact of levothyroxine therapy on bone. Some studies include measures of quality of life in evaluating treatment effectiveness, while others assess biochemical and physiological parameters. These differences need to be considered when interpreting the results of these studies.

Consistency and Contradictions of Results

The results of these studies offer valuable insights into the role of thyroxine and triiodothyronine in the treatment of hypothyroidism. These studies suggest that partial substitution of triiodothyronine for thyroxine might improve mood and neuropsychological function. However, the results of these studies are not all consistent. For example, one study shows that levothyroxine therapy has no effect on bone health, while another suggests it might have an impact. These contradictions necessitate further research.

Practical Applications and Considerations

While the results of these studies are valuable in optimizing treatment strategies for hypothyroidism, it's crucial to be cautious when applying these findings to individual patients. Each patient's symptoms and condition are unique, and treatment approaches need to be tailored accordingly. Additionally, these studies acknowledge that various factors can affect treatment outcomes, so the results might not apply to all patients.

Limitations of Current Research

These studies have some limitations. For instance, some studies have small sample sizes, which might limit the generalizability of their findings. Some studies haven't evaluated long-term outcomes. Additionally, many of these studies focus on specific racial or ethnic groups, and it remains uncertain whether the results are applicable to other populations.

Future Research Directions

These studies offer valuable information on the role of thyroxine and triiodothyronine in treating hypothyroidism, but further research is necessary. Specifically, studies should focus on the optimal dosage and duration of triiodothyronine therapy, the effects of triiodothyronine on various symptoms, and the risks and benefits of triiodothyronine therapy. Research is also needed to examine the effects of triiodothyronine in various age groups and racial/ethnic populations.

Conclusion

These studies provide valuable information about the treatment of hypothyroidism. They suggest that partially replacing thyroxine with triiodothyronine may improve mood and neuropsychological function. However, the results are not entirely consistent, and further research is necessary. These studies suggest the need for personalized treatment approaches because each patient's symptoms and conditions vary. Further research is essential to optimize hypothyroidism treatment strategies and to deepen our understanding of this disease.