AUTHOR=Zhang Hui , Tong Wenting , Zeng Weiyong , Luo Hongyan , Zhang Licai , Feng Jiasheng , Xiao Yang , Wang Gankun 

TITLE=Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1627787

DOI=10.3389/fendo.2025.1627787

ISSN=1664-2392

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