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

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 clini...

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Main Authors: Hui Zhang, Wenting Tong, Weiyong Zeng, Hongyan Luo, Licai Zhang, Jiasheng Feng, Yang Xiao, Gankun Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1627787/full
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author Hui Zhang
Hui Zhang
Wenting Tong
Weiyong Zeng
Hongyan Luo
Licai Zhang
Jiasheng Feng
Yang Xiao
Gankun Wang
author_facet Hui Zhang
Hui Zhang
Wenting Tong
Weiyong Zeng
Hongyan Luo
Licai Zhang
Jiasheng Feng
Yang Xiao
Gankun Wang
author_sort Hui Zhang
collection DOAJ
description 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
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spelling doaj-art-0b252541424948cab98ff08803c57f752025-08-20T03:51:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.16277871627787Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategiesHui Zhang0Hui Zhang1Wenting Tong2Weiyong Zeng3Hongyan Luo4Licai Zhang5Jiasheng Feng6Yang Xiao7Gankun Wang8Department of Urology, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaEndocrinology and Medical Sexology (ENDOSEX), Department of Experimental Medicine, University of Rome Tor Vergata, Rome, ItalyDepartment of Pharmacy, Gannan Healthcare Vocational College, Ganzhou, Jiangxi, ChinaDepartment of Urology, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaThe Ninth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Nephrology, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaDepartment of Urology, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaDepartment of Urology, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaDepartment of Thyroid Surgery, Dongguan Hospital affiliated to Guangzhou University of Chinese Medicine, Dongguan, ChinaA 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 managementhttps://www.frontiersin.org/articles/10.3389/fendo.2025.1627787/fullHashimoto’s thyreoiditisbiochemical euthroidismtherapyautoimmunity modulationsymptoms
spellingShingle Hui Zhang
Hui Zhang
Wenting Tong
Weiyong Zeng
Hongyan Luo
Licai Zhang
Jiasheng Feng
Yang Xiao
Gankun Wang
Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
Frontiers in Endocrinology
Hashimoto’s thyreoiditis
biochemical euthroidism
therapy
autoimmunity modulation
symptoms
title Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
title_full Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
title_fullStr Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
title_full_unstemmed Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
title_short Persistent symptoms in euthyroid Hashimoto’s thyroiditis: current hypotheses and emerging management strategies
title_sort persistent symptoms in euthyroid hashimoto s thyroiditis current hypotheses and emerging management strategies
topic Hashimoto’s thyreoiditis
biochemical euthroidism
therapy
autoimmunity modulation
symptoms
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1627787/full
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