Levothyroxine is a synthetic form of the thyroid hormone T4. For an underactive thyroid, it is the standard of care. The strongest questions about it are not whether it treats overt hypothyroidism, but who needs treatment when only a blood test is abnormal.
The standard, and why
The 2014 American Thyroid Association guideline is the reference for hypothyroidism. Its panel reviewed levothyroxine, thyroid extracts, combinations with T3 and other agents. It found insufficient consistent data to recommend a change from levothyroxine as the only drug needed to treat hypothyroidism.
Older adults with only a raised TSH
The TRUST trial randomized 737 adults aged 65 or older with persistent subclinical hypothyroidism to levothyroxine or placebo for one year. Levothyroxine lowered the blood TSH, but the primary symptom scores (hypothyroid symptoms and tiredness) did not improve. No significant excess of serious adverse events was seen in the treated group.
The pooled evidence
A 2019 BMJ guideline evidence review combined 21 randomized trials with 2,192 adults with subclinical hypothyroidism. Its conclusion, summarized by the NIHR, was that thyroid hormone treatment did not help adults with mildly abnormal thyroid tests. The earlier Cochrane review of 12 trials (about 350 people) found no difference in quality of life or symptoms, and no trial with cardiovascular outcomes.
Dosing and monitoring
Dose is set by the TSH result and by symptoms, and it is adjusted over time. Overtreatment has its own risks, so monitoring is part of any treatment plan.
What this does not say
- TRUST and the pooled reviews are about subclinical disease. They do not question treatment of overt hypothyroidism, which is established.
- The trials used levothyroxine tablets. Compounded thyroxine capsules have not been tested in their own trials.
- Averages across trials are not predictions for one person.
How we use this
Our physicians treat overt hypothyroidism with levothyroxine on the standard pathway. For a raised TSH without symptoms, the trials above are part of the conversation about whether treatment is needed now.
We do not promise energy, weight or mood changes from thyroid treatment; we check blood levels and symptoms together.
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- 1.Jonklaas J et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force. Thyroid 2014;24:1670-1751. Thyroid (ATA)
- 2.Stott DJ et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism (TRUST). N Engl J Med 2017;376:2534-2544. NEJM
- 3.Villar HC et al. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev 2007 (CD003419). Cochrane Library
- 4.Bekkering GE et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ 2019 (summary: NIHR Evidence). BMJ / NIHR Evidence