Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 18:16:1627787.
doi: 10.3389/fendo.2025.1627787. eCollection 2025.

Persistent symptoms in euthyroid Hashimoto's thyroiditis: current hypotheses and emerging management strategies

Hui Zhang #  1   2 , Wenting Tong #  3 , Weiyong Zeng  1 , Hongyan Luo  4 , Licai Zhang  5 , Jiasheng Feng  1 , Yang Xiao  1 , Gankun Wang  6
Affiliations
Review

Persistent symptoms in euthyroid Hashimoto's thyroiditis: current hypotheses and emerging management strategies

Hui Zhang et al. Front Endocrinol (Lausanne). .

Abstract

A substantial proportion of patients with Hashimoto's thyroiditis (HT) continue to experience persistent symptoms despite achieving biochemical euthyroidism, either with or without levothyroxine (LT4) replacement therapy. Several pathophysiological mechanisms have been proposed to explain this clinical phenomenon, including a reduced free triiodothyronine to free thyroxine (FT3/FT4) ratio and persistently elevated thyroid autoantibody titers. Escalation of LT4 monotherapy is generally discouraged due to an unfavourable risk-benefit profile. In contrast, combined LT4 and liothyronine (LT3) therapy may offer symptomatic improvement in selected patients, though robust criteria for selection remain undefined. More recently, total thyroidectomy has been explored as a therapeutic option in patients with refractory symptoms, demonstrating sustained improvements in health-related quality of life compared to medical therapy. However, this surgical approach must be balanced against potential perioperative risks and complications. Adjunctive therapies, including selenium and vitamin D supplementation, have shown modest benefit. In parallel, emerging evidence has highlighted the potential of traditional Chinese medicine (TCM)-notably, herbal medicine and acupuncture-as a complementary strategy for symptom relief, although further high-quality studies are warranted. This review synthesizes current insights into the mechanisms underlying residual symptoms in HT and critically evaluates contemporary and emerging therapeutic approaches aimed at improving patient-reported outcomes and long-term disease management.

Keywords: Hashimoto’s thyreoiditis; autoimmunity modulation; biochemical euthroidism; symptoms; therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Currently available strategies, and their mechanisms of action, for patients with Hashimoto thyroiditis (HT) with persisting symptoms despite normal thyroid hormone levels. Made with BioRender.com.
Figure 2
Figure 2
Most commonly employed acupoints for Hashimoto thyroiditis used in clinical trials. Made with BioRender.com.
See this image and copyright information in PMC

References

    1. Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. (2014) 99:923–31. doi: 10.1210/jc.2013-2409, PMID: - DOI - PubMed
    1. Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. (2018) 14:301–16. doi: 10.1038/nrendo.2018.18, PMID: - DOI - PubMed
    1. Hu X, Chen Y, Shen Y, Tian R, Sheng Y, Que H. Global prevalence and epidemiological trends of Hashimoto’s thyroiditis in adults: A systematic review and meta-analysis. Front Public Health. (2022) 10. doi: 10.3389/fpubh.2022.1020709, PMID: - DOI - PMC - PubMed
    1. Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. (2014) 13:391–7. doi: 10.1016/j.autrev.2014.01.007, PMID: - DOI - PubMed
    1. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Sawka AM, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. (2014) 24:1670–751. doi: 10.1089/thy.2014.0028, PMID: - DOI - PMC - PubMed

LinkOut - more resources