Traditional Chinese Medicine as an Adjunct in Hyperthyroidism Management: A Narrative Review of Pathophysiology, Proposed Mechanisms, and Clinical Evidence

Abstract

Hyperthyroidism, characterized by elevated serum thyroxine levels, can be classified into overt and subclinical forms. Untreated hyperthyroidism poses substantial health risks. Antithyroid drugs, radioactive iodine, and surgery are established conventional therapeutic options; however, their clinical application may be limited by relapse, adverse effects, contraindications, or patient preference. This narrative review examines the epidemiology of hyperthyroidism, particularly its association with iodine status, strong genetic predisposition, clinical manifestations predominantly seen in women of reproductive age, and diagnostic strategies. Pathophysiological mechanisms of different hyperthyroidism subtypes, including Graves’ disease and thyrotoxicosis caused by hyperfunctioning thyroid nodules, are discussed in detail. Furthermore, the perspective of Traditional Chinese Medicine (TCM) is explored, which attributes hyperthyroidism to Gan-Qi (liver-qi) disturbance and identifies exuberant liver fire as a core pathogenic factor. Multi-faceted mechanisms of TCM interventions, largely derived from network-pharmacology, pre-clinical findings and limited clinical data, represent proposed, hypothesis-generating pathways rather than firmly confirmed clinical effects. Available small-sized and heterogeneous randomized controlled trials suggest possible adjunctive benefits of TCM formulas and integrative therapies, such as Gardenia Qinggan Decoction combined with acupuncture, yet the overall certainty of evidence remains limited. Finally, this review highlights challenges in the standardization of TCM interventions, and underscores the necessity for unified quality-control metrics and standardized syndrome-differentiation criteria. Long-term comparative data evaluating sustained clinical outcomes of TCM-integrated management are still required.

Introduction

Hyperthyroidism is a clinical disorder characterized by elevated serum and tissue levels of thyroxine (T4), free triiodothyronine (T3), or both.¹ The term hyperthyroidism specifically denotes thyrotoxicosis resulting from excessive thyroid hormone production. Thyrotoxicosis is classified as “overt” when serum thyroid-stimulating hormone (TSH) concentrations are suppressed or undetectable, accompanied by elevated serum T4, total T3, or both levels exceeding the reference ranges. Conversely, “subclinical hyperthyroidism” is defined by low or undetectable TSH alongside normal serum T4 and total T3 concentrations.² Both overt and subclinical thyrotoxicosis are defined biochemically, regardless of clinical symptoms. Distinct etiologies contribute to thyrotoxicosis, including Graves’ disease, toxic nodular goiter, thyroiditis, and human chorionic gonadotropin-related thyrotoxicosis; these entities differ substantially in pathogenesis and conventional management, and therapeutic conclusions for one condition cannot be generalized to others. The prevalence of hyperthyroidism in the United States is estimated to be approximately 1.2%, with overt cases accounting for about 40% and subclinical cases for 60% of affected individuals.³

If left untreated, hyperthyroidism may cause severe multi-organ complications and, rarely, life-threatening outcomes. First-line conventional therapies are selected according to etiology and comprise antithyroid drugs, radioiodine ablation, and thyroidectomy. Nevertheless, these treatments may produce notable systemic adverse effects, and therapeutic response as well as tolerability are not always satisfactory. As an important part of complementary and alternative medicine, Traditional Chinese Medicine (TCM) has been applied for hyperthyroidism with multiple intervention modalities. It should be emphasized that TCM therapies including herbal formulas and acupuncture are not risk-free; herbal preparations may be associated with adverse events, herb-drug interactions, iodine exposure, hepatotoxicity, product contamination, and manufacturing quality-control concerns. Despite these safety caveats, accumulating clinical and mechanistic data suggest potential therapeutic value of TCM-related interventions for hyperthyroidism. This review examines TCM as an adjunctive approach in hyperthyroidism, focusing on proposed mechanisms, clinical evidence, safety, and research gaps.

Methods

This manuscript is a narrative review prepared in accordance with SANRA guidelines for narrative reviews.

Article type: Narrative review synthesizing pre‑clinical and clinical evidence for TCM as adjunctive therapy for hyperthyroidism.

Databases searched: PubMed, Embase, Web of Science, CNKI, WanFang.

Search dates: Inception to April 2026.

Languages: English and Chinese.

Search terms: Hyperthyroidism, Graves disease, Traditional Chinese Medicine, Chinese herbal medicine, acupuncture, syndrome differentiation, network pharmacology, molecular docking, metabolomics, animal experiment, randomized controlled trial.

Inclusion criteria: (1) Original human clinical studies (randomized controlled trials, observational studies) evaluating TCM‑related interventions for hyperthyroidism; (2) Pre‑clinical studies: animal experiments, cell experiments, network pharmacology, molecular docking, metabolomics investigating TCM for hyperthyroidism; (3) Reviews relevant to TCM and hyperthyroidism.

Exclusion criteria: Case reports, case series with fewer than 10 participants, conference abstracts without full‑text, non‑human studies without clear relevance to hyperthyroidism.

Study selection: Titles and abstracts were screened, followed by full‑text assessment for eligibility. Potentially relevant articles were retrieved and evaluated for inclusion.

**Data extraction**: We extracted study characteristics, intervention details, outcome data, and key findings. **Evidence was grouped by study type: human RCTs, human observational studies, animal studies, cell experiments, network pharmacology, molecular docking, and metabolomics.**

Critical appraisal: For included randomized controlled trials, study quality was assessed using the CASP RCT checklist, evaluating randomization, allocation concealment, blinding, baseline comparability, participant attrition, intention‑to‑treat analysis, adverse‑event reporting, and follow‑up completeness.

Evidence grading: The strength of evidence for each mechanistic and clinical claim was graded using CEBM (Oxford Centre for Evidence‑Based Medicine) levels of evidence, summarized in Table 1.

Table 1.

Summary of Evidence Strength (CEBM Levels)

Reference	Study Type	Main Claim	CEBM Evidence Level	Limitations
4	RCT	Danzhi Xiaoyao capsules combined with methimazole improves thyroid-related indices	2	Small sample, unclear blinding, short follow-up
5	Animal + metabolomics	Cold-nature herbs regulate metabolism in hyperthyroid rats	5	Pre-clinical, cannot confirm human clinical efficacy

Definition of Hard Clinical Outcomes and Surrogate Outcomes

Hard Clinical Outcomes

For hyperthyroidism were predefined as: sustained remission after stopping therapy, relapse rate with adequate follow‑up, time to biochemical euthyroidism, TRAb normalization, thyroid storm, atrial fibrillation, heart failure, fracture, hospitalization, mortality, patient‑reported quality of life, serious adverse events.

Surrogate or Mechanistic Outcomes

Thyroid‑hormone concentrations, inflammatory markers, oxidative‑stress markers, molecular targets, and pathway‑enrichment results. These surrogate markers are not equivalent to direct clinical patient benefit.

Important Caveat

Findings from animal‑model experiments, cell assays, metabolomics, network pharmacology, and molecular docking are hypothesis‑generating. Such mechanistic evidence cannot independently establish clinical effectiveness, relapse‑prevention capacity, clinical safety, or superiority compared with standard antithyroid pharmacotherapy.

Epidemiology

The global epidemiology of thyroid disorders is intricately linked to the iodine nutritional status of populations.^6,7 In regions with sufficient iodine intake, both overt and subclinical hyperthyroidism affect approximately 0.5% of the population, corresponding to an annual incidence rate of approximately 50 cases per 100,000 individuals.^8–10 Among these populations, Graves’ disease (GD) constitutes the predominant etiology.¹¹ Conversely, in iodine-deficient regions, the combined incidence of overt and subclinical hyperthyroidism rises substantially, reaching 10–15%, with toxic multinodular goiter occurring more frequently than GD.^12–14 Implementation of public health interventions aimed at correcting iodine deficiency may initially provoke a transient increase in hyperthyroidism incidence, which subsequently declines to levels observed in iodine-sufficient areas.^15,16

Specifically, the incidence of GD in iodine-replete regions is estimated at 20–30 cases per 100,000 individuals per year, with peak occurrence between the third and fifth decades of life and a female-to-male ratio of approximately 5–6:1.^11,12 The annual incidence of toxic nodular goiter ranges from 3 to 6 cases per 100,000 persons in iodine-sufficient areas and increases to 20 to 40 cases per 100,000 in iodine-deficient regions. This condition predominantly affects individuals over 50 years of age and exhibits a higher prevalence among women than among men¹⁴ (see Figure 1).

Figure 1.

Epidemiology and risk factors of hyperthyroidism. This figure summarizes the epidemiologic patterns and major determinants of hyperthyroidism. Left: global distribution related to iodine nutritional status—in iodine-sufficient regions, Graves’ disease (GD) usually predominates, whereas in iodine-deficient regions, toxic multinodular goiter (TNG) is more frequent. Center: principal risk factors, including genetic susceptibility (eg, HLA, CTLA4, PTPN22, SH2B3), environmental factors (smoking, infection, psychological stress, medications), and other contributors (TSH-secreting adenoma, pregnancy, neoplasms). Right: susceptible populations, characterized by female predominance (female:male ≈ 5–6:1) and peak incidence at 30–50 years of age. Original figure created by the authors.

Abbreviations: GD, Graves’ disease; TNG, toxic multinodular goiter; TSH, thyroid-stimulating hormone; HLA, human leukocyte antigen; CTLA4, cytotoxic T-lymphocyte–associated protein 4; PTPN22, protein tyrosine phosphatase non-receptor type 22; SH2B3, SH2B adaptor protein 3.

Genetics

Genetic investigations involving twin cohorts from Danish and Swedish populations have revealed pronounced genetic clustering, with concordance rates observed between 20% and 35% in monozygotic twins, contrasted with only 2% to 3% in dizygotic twins.^17,18 These findings align with a model positing that genetic factors contribute to approximately 60% to 80% of the risk for GD.^17,18 Heritability estimates can also be derived from sibling recurrence hazard ratios. For instance, a Hungarian study reported that 23 out of 435 individuals suspected of GD (5.3%) had siblings diagnosed with the disease, compared with a baseline population prevalence of 0.65%.¹⁹ Similarly, a study conducted in Newcastle, United Kingdom, found that 15 of 190 GD suspects (7.9%) had affected siblings, relative to a background prevalence of 0.8%.²⁰ From these data, a recurrence hazard ratio ranging from 8 to 10 for GD was calculated, which is comparable to ratios reported for rheumatoid arthritis (8), type 1 diabetes mellitus (15), and multiple sclerosis (20).²¹ These observations underscore that GD, akin to many autoimmune disorders, represents a complex genetic trait characterized by strong familial aggregation that lacks a classical Mendelian inheritance pattern.^17,18,20,21

Initial genetic studies concentrated on alleles within the major histocompatibility complex (MHC), primarily owing to the availability of reliable genotypic markers at this locus. Serological typing of human leukocyte antigen (HLA) first identified a robust association between MHC alleles located on the short arm of chromosome 6 and GD.²² Subsequent investigations in populations of European descent have refined this association, consistently implicating the haplotype HLA-DRB1*0301-DQB1*0201-DQA1*0501, with odds ratios ranging from 2 to 3 relative to unaffected controls.^23,24 In contrast, distinct HLA associations have been documented in Asian populations, including DRB1*0405 and DRB1*1403 in Japanese cohorts,^25,26 DRB1*0803 and DRB1*1602 in Korean populations,²⁷ and DRB1*1602 in Thai individuals.²⁸ Notably, the DRB1*0301 allele encodes an arginine residue at position 74 of the MHC-DRβ chain, which is hypothesized to modify the peptide-binding groove of the MHC molecule, thereby facilitating the enhanced binding of T lymphocyte peptide antigens.²⁹ However, given that only approximately 50% of European GD patients carry the DRB1*0301 haplotype, MHC restriction involving a single antigenic peptide may not account for all GD cases.

Following the identification of the MHC locus as relevant to GD susceptibility, candidate gene studies examined polymorphisms in the cytotoxic T lymphocyte antigen-4 (CTLA4) gene, which was newly characterized at the time. CTLA4 represents a compelling candidate gene for autoimmune diseases due to its role as a negative covalent regulatory molecule that functions as a “second signal” modulating T-cell receptor activation in response to MHC antigen presentation at immune synapses. Despite the modest sample size of the initial study, which included only 133 GD patients,³⁰ the findings were strongly supportive and have since been replicated in over 50 subsequent studies.^30,31

Although candidate gene approaches have successfully identified several GD susceptibility genes with substantial effect sizes, this methodology is inherently limited in its capacity to uncover novel biological mechanisms underlying the disease. To address this limitation, researchers from the United States and Europe employed a discovery-driven genome-wide association study (GWAS) approach focusing on autoimmune thyroid disease (AITD) pedigrees with multiple affected relatives.^32,33 A US-based study involving 56 multigenerational families confirmed the established MHC linkage³⁴ and identified novel linkage signals at three additional loci: GD-1 (D14S81 on chromosome 14q31), GD-2 (D20S195 on chromosome 20q11.2), and GD-3 (DXS8020 on chromosome Xq21).³² Subsequent replication efforts in a larger cohort of 102 families corroborated the linkages at 14q31 and 20q11 but failed to replicate the association on the X chromosome.³⁵

A comprehensive GWAS encompassing a mixed cohort of 30,234 individuals with AITD and 72,172 controls from Iceland and the UK Biobank identified 99 genome-wide significant associations across 93 loci.³⁶ Remarkably, 84 of these genes have not previously been implicated in AITD. Systematic annotation supported 37 candidate genes, with 24 encoded proteins participating directly or indirectly within a shared functional network. The study also uncovered two novel, albeit less frequent, variants exerting relatively large effects on AITD susceptibility: an intronic variant in FLT3 (rs76428106-C) and a missense variant in ADCY7 (rs78534766-A). Notably, FLT3 variants have not previously been associated with any disease, whereas ADCY7 variants have been linked to ulcerative colitis. The FLT3 variant introduces a cryptic splice site and premature stop codon, which is predicted to yield a truncated protein. This association was further replicated in patients with systemic lupus erythematosus, rheumatoid arthritis, or celiac disease.³⁶

Overall, only 15 of the 99 identified variants exhibited an effect size exceeding an odds ratio of 1.10. These included previously established common alleles (eg, HLA, CTLA4, PTPN22, and SH2B3) as well as rare variants detectable only through sufficiently powered cohorts. Many genetic variants (eg, CTLA4, PTPN22, and RNASET2) demonstrated similar effects on both GD and Hashimoto’s thyroiditis, whereas a subset, including FLT3 variants, appeared to predispose to Hashimoto’s thyroiditis while conferring some protection against GD. Despite representing the largest genetic study of AITD to date, it is important to note that only approximately 2,400 GD patients were included, compared to 27,000 individuals with hypothyroidism or Hashimoto’s thyroiditis. This design choice, which treats GD as a sub-phenotype within a broader analysis, may limit the power to detect GD-specific genetic loci. In conclusion, these findings suggest that considerable knowledge remains to be gained regarding the genetic susceptibility to GD.

Clinical Manifestations

Hyperthyroidism predominantly affects women of reproductive ages. Clinical manifestations commonly include psychological stress, heat intolerance, palpitations, and weight loss despite an increased appetite. Physical examination may reveal signs such as tendon hyperreflexia, fine finger tremors, moist skin, tachycardia, and goiter.³⁷ These signs and symptoms are observed in over 50% of overt hyperthyroidism cases.^37,38 Given that thyroid hormones enhance systemic metabolism, less frequent systemic manifestations may be observed in various tissues.

The clinical presentation of hyperthyroidism is modulated by factors such as sex, age, and underlying etiology. The incidence of hyperthyroidism is reported to be four–seven times higher than that in the general population.³⁹ It is most prevalent in women aged 20–50 years. In elderly individuals (> 65 years), hyperthyroidism tends to be asymptomatic and less severe than in younger patients; however, the incidence of atrial fibrillation is notably higher in this age group.^40–42 GD typically manifests with more severe symptoms than toxic adenomas or toxic multinodular goiters do. Toxic adenoma is more frequently diagnosed between the ages of 30 and 60 years, whereas toxic multinodular goiter is more common after 50 years of age.⁴² Over the past four decades, the severity of clinical signs associated with hyperthyroidism has diminished, a trend potentially attributable to earlier diagnosis facilitated by sensitive thyroid hormone assays, broader implementation of iodine prophylaxis, and a decline in smoking prevalence.^38,43

Diagnosis

When hyperthyroidism is clinically suspected, biochemical testing is essential to confirm or exclude a diagnosis. TSH levels within the reference range (0.4–4.0 mU/L) effectively rule out hyperthyroidism, except in rare cases involving TSH-secreting pituitary adenomas or thyroid hormone resistance, where TSH may be normal or slightly elevated. If TSH is suppressed (<0.4 mU/L), free thyroxine (FT4) should be measured. Elevated FT4 levels support the diagnosis of thyrotoxicosis; however, normal FT4 levels in the context of low TSH levels may indicate T3 toxicosis^42,44 or subclinical hyperthyroidism, the latter defined by suppressed TSH with normal FT4 and free triiodothyronine (FT3) levels. Approximately 10% of the patients with subclinical hyperthyroidism progress to T3 toxicosis. Although assay interference is uncommon, consultation with the biochemical laboratory is advised if discrepancies arise between TSH and FT4 results or if the results appear inconsistent.

Upon biochemical confirmation of hyperthyroidism, further diagnostic evaluation is necessary to determine the underlying etiology of thyrotoxicosis. GD was the most prevalent cause, followed by toxic multinodular goiter and solitary toxic adenoma. Clinical features such as diffuse toxic goiter with pulsatility or thyroid-associated ophthalmopathy strongly suggest GD.⁴² In suspected cases of GD, measurement of thyrotropin receptor antibodies (TRAb)^3,45 is recommended. TRAb can be detected via immunoassays, such as TSH-binding inhibitory immunoglobulin (TBII) assays, which identify antibodies binding to the TSH receptor, or through cellular bioassays that assess the functional activity of these antibodies, distinguishing stimulatory from blocking effects.⁴⁶ Current TBII assays demonstrate sensitivity and specificity exceeding 95%, whereas bioassays approach nearly 100% sensitivity and specificity.⁴⁵

In addition to TRAb testing, thyroid scintigraphy and ultrasonography are also effective diagnostic modalities.³⁷ Uptake of radioactive iodine or other tracers is increased in conditions involving TSH receptor activation, whether due to stimulating antibodies, human chorionic gonadotropin (HCG), or activating mutations in the G-protein alpha subunit of the TSH receptor. Conversely, destructive thyroiditis leads to follicular damage, releasing iodine- and hormone-rich contents into circulation, resulting in thyroid toxicity with low or absent radioactive iodine uptake. Ultrasonography, particularly color Doppler flow imaging, can differentiate hyperthyroidism, characterized by hypervascularity in GD, toxic adenoma, and toxic multinodular goiter, from destructive thyroiditis and extrathyroidal thyrotoxicosis, which exhibit reduced or absent blood flow.^3,45 Given its convenience and avoidance of radioactive exposure, ultrasonography has become the preferred imaging technique in the evaluation of hyperthyroidism^39,47 (see Figure 2).

Figure 2.

Diagnostic workflow and etiological differentiation of hyperthyroidism. Diagnosis proceeds from biochemical confirmation to etiological differentiation. Biochemical diagnosis: suppressed TSH (<0.4 mU/L) prompts concurrent measurement of free thyroxine (FT4) and free triiodothyronine (FT3). Elevated FT4 indicates thyrotoxicosis; normal FT4 with elevated FT3 indicates T3 toxicosis; normal FT4 and FT3 with suppressed TSH indicate subclinical hyperthyroidism. Etiological differentiation: TSH receptor antibody (TRAb) testing is used to support the diagnosis of Graves’ disease (GD). Radionuclide imaging shows increased RAIU in GD and toxic multinodular goiter (TNG) but decreased uptake in thyroiditis. Color Doppler ultrasound shows hypervascularity in GD, TNG, and toxic adenoma (TA), whereas reduced flow suggests thyroiditis. Arrows indicate the sequential diagnostic pathway. Original figure created by the authors based on established diagnostic principles summarized in the manuscript.

Abbreviations: TSH, thyroid-stimulating hormone; FT4, free thyroxine; FT3, free triiodothyronine; TRAb, TSH receptor antibody; RAIU, radioactive iodine uptake; GD, Graves’ disease; TNG, toxic multinodular goiter; TA, toxic adenoma.

Pathophysiological Mechanisms

GD

GD represents a subset within the spectrum of autoimmune thyroid disorders, and its pathogenesis is characterized by a multifaceted interaction between genetic predispositions and environmental influences, culminating in the breakdown of immune tolerance to thyroid-specific antigens.^48,49 A central aspect of GD pathophysiology is the Th2-mediated immune response, which generates IgG antibodies that target TSH receptors on thyroid follicular cells. This antibody-receptor interaction promotes enhanced synthesis and secretion of thyroid hormones, follicular cell hyperplasia, and development of goiter.^50,51 Genetic susceptibility is associated with polymorphisms in immunoregulatory genes, including HLA-BA, HLA-DR3, CD40, CTLA4, FCRL3, IL2RA, and PTPN22, as well as genes encoding thyroid autoantigens; however, the precise mechanisms underlying these associations remain unclear.^52,53 Established environmental contributors include smoking, iodine intake, psychological stress, pregnancy and the postpartum period, infection with Yersinia enterocolitica, and exposure to certain pharmacological agents. Additional factors potentially implicated include selenium status, alterations in the gut microbiome, viral infections, and exposure to endocrine-disrupting chemicals.^54–56 Furthermore, similar to other autoimmune conditions, skewed X chromosome inactivation may significantly contribute to the higher prevalence of GD observed in females.

HGG Associated Thyrotoxicosis

HCG exhibits thyroid-stimulating properties by binding to the thyroid-stimulating hormone receptor (TSHR) and activating adenylyl cyclase.⁵⁷ During normal pregnancy, serum HCG levels reach their peak between 9 and 12 weeks of gestation, coinciding with a decrease in serum TSH levels. At an average HCG concentration of 52,400 IU/L, approximately 18% of pregnant women have TSH levels below 0.2 mU/L. Furthermore, when serum HCG concentrations exceed 200,000 IU/L, approximately 32% of patients exhibit TSH concentrations or ≤ 0.2 mU/L. Elevated serum FT4 levels are observed in 32% of patients with HCG concentrations above 200,000 IU/L, increasing to 80% when HCG levels surpass 400,000 IU/L.⁵⁸ Elevated HCG concentrations are also associated with hyperemesis gravidarum and transient thyrotoxicosis during pregnancy, which becomes clinically apparent when HCG levels exceed 180,000 IU/L.^59,60 Additionally, certain trophoblastic tumors secrete HCG, particularly the asialo-HCG variant, which possesses potent TSH-like activity and can induce overt hyperthyroidism when produced in excessive amounts.^57,61

Purinergic System

Numerous investigations have been conducted to elucidate the impact of hyperthyroidism on ectonucleotidase activity, nucleotide hydrolysis, and the extracellular nucleotide milieu. Meis et al⁶² demonstrated that administration of T4 to rabbits augmented uncoupled ATPase activity and thermogenesis within the sarcoplasmic reticulum vesicles. Additional research has indicated that hyperthyroidism predominantly suppresses the hydrolysis of ATP, ADP, and AMP in rat serum.⁶³ Moreover, patients with hyperthyroidism exhibit significantly elevated ATP concentrations along with increased expression levels of P2X3 and P2X7 mRNA compared to healthy controls.⁶⁴

As previously noted, numerous central nervous system (CNS) manifestations associated with hyperthyroidism are linked to alterations in the purinergic system. Inhibition of ADP and AMP hydrolysis has been observed not only in the hippocampus, cerebral cortex, and serum of rats aged 5–60 days, but also in the hippocampus of 11-month-old rats. In contrast, an increase in AMP hydrolysis was detected in the cerebral cortex of 11-month-old rats.⁶⁵ Furthermore, hydrolysis of ATP, ADP, and AMP in the spinal cord of hyperthyroid rats aged 60 and 330 days was markedly reduced, whereas a pronounced increase in ADP and AMP hydrolysis was noted in 5-day-old rats.⁶⁶ Hyperthyroidism also diminishes the expression of 5’-nucleotidase, significantly inhibiting ATP, ADP, and AMP hydrolysis in hippocampal and cerebral cortical slices from adult rats.⁶⁷ Activation of adenosine A1 receptors modulates both behavioral and biochemical parameters in hyperthyroid rats, implying that certain effects of hyperthyroidism are mediated via the adenosine A1 receptor pathways.⁶⁸ Collectively, these findings suggest that thyroid hormones influence CNS function through mechanisms involving the purinergic system, with effects varying according to the brain region and developmental stage.

The purinergic system also plays a role in vascular regulation under hyperthyroid conditions. In hyperthyroid rats, AMP hydrolysis in platelets is increased, whereas ATP and ADP hydrolysis remain unchanged.⁶⁹ Conversely, the activities of nucleoside triphosphate diphosphohydrolase (NTPD) and exo-5’-nucleotidase in platelets are decreased, whereas adenosine deaminase (ADA) activity is elevated.⁷⁰ These observations indicate that hyperthyroidism modulates extracellular enzyme activity, thereby altering adenosine concentration within platelets. Given that adenosine inhibits platelet aggregation and acts as a potent vasodilator, these results enhance our understanding of vascular phenomena associated with thyroid disorders.

Experimental studies have further established the critical role of purinergic signaling in cardiovascular physiology. Cardiac levels of A1 adenosine receptors correlate with the heart rate and cardiac efficiency.⁷¹ ADA deficiency markedly improves ischemic tolerance, whereas deficiency of A1 adenosine receptors impairs it.⁷² Additionally, triiodothyronine (T3) modulates E-NTPD enzyme activity, leading to increased hydrolysis of ATP and ADP in cardiac myocytes.⁷³ Elevated intracellular adenosine levels have been proposed to enhance the inhibitory response of hyperthyroid guinea pig atria to A1 adenosine receptor agonists.⁷⁴ Hyperthyroidism also augments adenosine influx without altering the predominant direction of adenosine transport in guinea pig atria.⁷⁵ Furthermore, thyroid hormones influence adenosine production by modulating the activity and expression of 5’-nucleotidase within the soluble fraction of cardiac tissue.⁷⁶

Toxic Nodular Goiter

Thyroid nodules are prevalent in the general population, particularly in regions with iodine deficiency. This deficiency exerts a chronic irritative influence on the thyroid gland, which can result in the development of diffuse or nodular goiter, and may ultimately progress to thyroid autonomic disease.⁷⁷ Approximately 5% of thyroid nodules evolve into functional autonomic disorders, manifesting either as solitary toxic adenomas or components of a multinodular goiter. Activating mutations in the thyrotropin receptor (TSHR) gene and the Gs protein alpha subunit gene (GNAS) lead to sustained activation of the cyclic adenosine monophosphate (cAMP) or protein kinase A signaling pathways. This persistent signaling enhances TSH synthesis and secretion, thereby inducing hyperthyroidism.⁷⁷ Additionally, secondary mutations in EZH1 have been identified in approximately 25% of cases, further promoting thyroid cell proliferation.⁷⁸

TSH-Secreting Pituitary Adenoma

TSH-secreting pituitary adenoma is an uncommon disorder that typically manifests as a macroadenoma, leading to visual field impairments, headaches, and mild hyperthyroidism, predominantly affecting individuals in their fifth and sixth decades of life.⁷⁹ Diagnosis is frequently delayed, particularly in cases in which serum TSH levels remain within the normal range. Comparable thyroid function test results can also be observed in patients with thyroid hormone resistance. Definitive diagnosis of a TSH-secreting pituitary adenoma can be achieved through pituitary contrast imaging, elevated serum concentrations of the glycoprotein alpha subunit, attenuated response to thyrotropin-releasing hormone (TRH), and inadequate suppression of TSH following administration of exogenous triiodothyronine (T3).⁷⁹

Thyroiditis

Thyroiditis arises from diverse etiologies, including infectious agents, autoimmune mechanisms, pharmacological interventions, systemic diseases, environmental influences, and the postpartum period.⁸⁰ Thyrotoxicosis manifests when inflammatory or toxic damage to thyroid follicles leads to the uncontrolled release of preformed thyroid hormones. This thyrotoxic state is typically transient and self-limiting, resolving within one–four months as thyroid hormone reserves are depleted or the inflammatory response diminishes.

Lymphocytic thyroiditis represents painless autoimmune thyroid inflammation that may be accompanied by thyrotoxicosis. It constitutes a subset within the spectrum of autoimmune thyroid disorders, encompassing clinical variants, such as postpartum thyroiditis and Hashimoto’s thyroiditis. Unlike Graves’ disease, lymphocytic thyroiditis is predominantly characterized by Th1 and Th17 immune responses, which are associated with lymphocytic infiltration of the thyroid, formation of lymphoid follicles, and atrophy of thyroid follicles. The majority of affected individuals exhibit circulating autoantibodies targeting key thyroid antigens, namely, thyroid peroxidase (TPO) and thyroglobulin.^48,81 Postpartum thyroiditis, a specific subtype, affects approximately 5% of women within the first year after childbirth, with roughly half of these cases progressing to thyrotoxicosis.^82,83

Subacute thyroiditis is clinically distinguished by thyroid gland pain, which may be accompanied by fever and systemic inflammatory symptoms before the onset of morbidity. It is hypothesized to result from a post-viral inflammatory process, particularly in individuals with HLA-B35 and HLA-B67 genotypes, following viral infections. This condition is characterized histologically by granulomatous inflammation, giant cell formation, and interlobular infiltration by mixed mononuclear cells, including monocytes and lymphocytes.⁸⁴ Epidemiological and virological investigations have implicated several viruses, such as mumps, echovirus, coxsackievirus, and SARS-CoV-2, in the pathogenesis of thyroiditis.^85–89 Although numerous case reports have documented subacute thyroiditis subsequent to COVID-19 vaccination,⁹⁰ a large population-based study involving 2.3 million vaccine recipients found no increased incidence of thyroiditis within 56 days post-vaccination compared with baseline rates, suggesting that any observed association may be coincidental.⁹¹

The classical clinical course of destructive thyroiditis is triphasic, beginning with a thyrotoxic phase lasting approximately one–three months, followed by a hypothyroid phase that may persist for up to six months, culminating in spontaneous restoration of euthyroid status.⁹² The clinical presentation of destructive thyrotoxicosis is heterogeneous; some patients experience only mild thyrotoxic or hypothyroid symptoms and many cases may remain clinically unrecognized.

Several pharmacological agents have been implicated in thyroiditis induction. Immune checkpoint inhibitors are now the standard treatment for various malignancies and are associated with thyroiditis in approximately 10% of treated patients,^93,94 with a higher incidence observed in individuals with pre-existing autoimmune thyroid disease.^95,96 Thyroiditis occurs more frequently with programmed cell death-1 (PD-1) inhibitors or combination immunotherapy than with monotherapy involving programmed cell death ligand-1 (PD-L1) inhibitors or cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors.⁹⁷ Additionally, thyrotoxicosis develops in 3–5% of patients receiving interferon-alpha therapy⁹⁸ (see Figure 3).

Figure 3.

Pathophysiological mechanisms of hyperthyroidism. Seven major etiological pathways are illustrated. Graves’ disease: autoimmune Th2-type immune response generates IgG stimulating antibodies that activate the TSH receptor (TSHR). HCG-related hyperthyroidism: elevated human chorionic gonadotropin (HCG) mimics TSH activity and stimulates TSHR, producing gestational thyrotoxicosis. Purinergic system dysregulation: T3/T4 disrupt ATP/ADP/AMP hydrolysis, linking energy metabolism with neural regulation. TNG/adenoma: somatic TSHR/Gsα mutations activate the cAMP/PKA pathway. TSH-secreting pituitary adenoma: excess TSH secretion or impaired feedback regulation. Thyroiditis: inflammatory follicular destruction releases preformed thyroid hormones; importantly, thyroiditis is not uniformly antibody-mediated. Lymphocytic (autoimmune) thyroiditis involves Th1/Th17 responses with elevated TPOAb/TgAb, whereas subacute thyroiditis is typically a post-viral inflammatory response without antibody predominance. Other factors: immune checkpoint inhibitors (PD-1/PD-L1 blockade) may induce immune-mediated thyroid injury. Arrows indicate mechanistic progression from etiology to molecular/cellular events. Original figure created by the authors based on mechanisms summarized in the manuscript.

Abbreviations: TSHR, TSH receptor; HCG, human chorionic gonadotropin; TNG, toxic multinodular goiter; TPOAb, thyroid peroxidase antibody; TgAb, thyroglobulin antibody; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A.

Basic Theory of TCM in Treating Hyperthyroidism

In TCM, goiter has historically been classified under the category of “gall disease.” According to the Clinical Terminology of Diagnosis and Treatment of Traditional Chinese Medicine,⁹⁹ goiter is categorized as a disorder of “gall qi,” primarily attributed to emotional injury, yin deficiency, and qi stagnation. These pathological changes result in the accumulation of phlegm and qi as well as the transformation of fire into yin. Clinically, the condition is characterized by anterior neck swelling and increased appetite accompanied by weight loss, irritability, palpitations, heat intolerance with sweating, hand tremors, and exophthalmos.

Contemporary TCM scholars have developed a more nuanced understanding of the etiology of hyperthyroidism. Dan et al¹⁰⁰ identified “liver depression” as the principal pathogenic mechanism. Professor Hu Hengchang et al¹⁰¹ emphasized the significant involvement of the lung and stomach in disease onset and proposed three key pathways: (1) emotional injury damaging the spleen, subsequently affecting the lung and stomach; (2) emotional injury directly impairing the liver, which then impacts the lung and stomach; and (3) vulnerability of the lung and stomach to exogenous pathogenic factors. Additionally, individual constitutional differences influence susceptibility, with TCM theory positing that women, who are considered to be “born with liver,” exhibit a higher prevalence of hyperthyroidism compared to men. Current research corroborates that the predominant constituents associated with hyperthyroidism include yin deficiency, qi stagnation, and qi deficiency.^102–104

Professor Tong Xiaolin, a specialist in TCM endocrinology and metabolism, asserts that the core pathological processes underlying hyperthyroidism involve exuberant liver fires, phlegm accumulation, and blood stasis.¹⁰⁵ Therapeutic strategies thus focus on clearing and protecting the liver, utilizing representative herbal medicines, such as Prunella vulgaris, Schisandra chinensis, and Dioscorea bulbifera. In summary, hyperthyroidism is primarily localized in the liver and its pathological nature is predominantly characterized by solid masses arising from qi stagnation, phlegm coagulation, and blood stasis (see Figure 4).

Figure 4.

Basic TCM pathogenesis and therapeutic principles for hyperthyroidism. This figure links triggers, core pathogenesis, syndrome patterns, and corresponding treatment principles. Triggers (emotional stress, exogenous pathogens, and constitutional susceptibility) lead to the core pathogenesis of impaired Liver Qi coursing. On this basis, four commonly recognized syndrome patterns and their paired therapeutic principles are illustrated: Liver Qi stagnation, characterized by impaired Qi circulation, for which the corresponding principle is to soothe the Liver and regulate Qi; concurrent phlegm and blood stasis, associated with goiter formation, for which the corresponding principle is to regulate Qi and resolve phlegm; blood stasis obstructing the collaterals, associated with persistent nodules, for which the corresponding principle is to activate blood and resolve stasis; and Yin deficiency with hyperactive fire, characterized by internal heat disturbing the mind, for which the corresponding principle is to nourish Yin and clear heat. These pairings represent syndrome-based therapeutic strategies in TCM clinical reasoning rather than validated molecular pathways. Notably, TCM descriptors such as “Liver” refer to functional systems within TCM theory and should not be interpreted as anatomical organs. Original figure created by the authors.

Effect of TCM on the Pathological Mechanism of Hyperthyroidism

TCM influences the pathological mechanisms underlying hyperthyroidism via multiple pathways. Several studies have examined the potential mechanisms by which TCM treats hyperthyroidism by integrating network pharmacology with experimental validation. For instance, research has demonstrated that diosgenin, a compound found in the rhizome of Dioscorea nipponica Makino, inhibits phosphorylation and subsequent inactivation of IGF-1R. This inhibition suppresses the phosphorylation and activation of the PI3K-AKT and Rap1-MEK signaling pathways, thereby promoting apoptosis and mitigating GD-induced hyperthyroidism. This finding elucidates a novel mechanistic basis for the therapeutic effects of TCM in hyperthyroidism management.¹⁰⁶ These pre-clinical findings provide mechanistic hypotheses but do not prove clinical efficacy in human patients.

Wang et al⁵ reported that four representative cold-natured TCM herbs modulate energy metabolism, glutathione metabolism, and other metabolic pathways in hyperthyroid rat models. These herbs also attenuated inflammatory responses and enhanced thyroid hormone synthesis, collectively alleviating hyperthyroid symptoms. This evidence suggests that TCM exerts its therapeutic effects by regulating metabolic and inflammation-associated pathological processes. Similarly, Liu Linlin et al¹⁰⁷ observed that ginseng-based treatments with varying properties ameliorated hyperthyroidism in rats by modulating the hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, and hypothalamic-pituitary-gonadal axes. These findings imply that TCM may influence the pathological progression of hyperthyroidism through regulation of the neuroendocrine system. These pre-clinical findings provide mechanistic hypotheses but do not prove clinical efficacy in human patients.

Several studies combining traditional Chinese medical theory with contemporary biomedical techniques have revealed the multi-target and multimodal characteristics of TCM in hyperthyroidism treatment. For example, Song Dan et al¹⁰⁸ employed network pharmacology and molecular docking to investigate the mechanisms of Danggui Liuhuang Decoction. Their results indicated that the active constituents of the decoction interact with multiple targets, including MAPK1, CCND1, AKT1, and TNF, and are involved in signaling pathways such as HIF-1 and FoxO. This study preliminarily elucidated the multi-component, multi-target, and multi-pathway therapeutic profile of the Danggui Liuhuang Decoction in hyperthyroidism.

Furthermore, Wei Maoying et al¹⁰⁹ integrated metabolomics with target prediction to assess the effects of four typical cold-natured TCM herbs in hyperthyroid rats. Their findings revealed that these herbs regulate energy metabolism and inflammation-related pathways, highlighting the advantages of combining traditional Chinese and Western medical approaches to uncover the mechanisms of TCM in hyperthyroidism treatment. This integrative strategy not only aligns with the holistic principles of TCM, but also leverages precise modern biomedical technologies to deepen the understanding of the molecular mechanisms underlying TCM’s therapeutic effects of TCM, thereby providing a theoretical foundation for developing more effective treatment regimens. These pre-clinical findings provide mechanistic hypotheses but do not prove clinical efficacy in human patients.

Clinical Evidence

All included TCM interventions in this review are evaluated as adjunctive therapies combined with conventional antithyroid-drug-based standard care. Evidence is grouped by intervention and comparator. Most trials rely heavily on surrogate biochemical or syndrome-based endpoints; high-quality long-term data on hard clinical outcomes (post-withdrawal sustained remission, long-term relapse) remain scarce. Composite “total effective rate” from domestic studies is reported but interpreted cautiously, with priority given to internationally recognized objective indices (FT3, FT4, TSH, TRAb, quality of life, adverse events).

Group 1: Herbal Formula Plus Methimazole versus Methimazole Alone

Danzhi Xiaoyao capsules plus methimazole vs methimazole alone.⁴ Study design: RCT; diagnostic criteria for hyperthyroidism with liver-depression-spleen-deficiency TCM syndrome; n=70 (35 per-group). Intervention: Observation group: Danzhi Xiaoyao capsules + methimazole; Control group: methimazole monotherapy; treatment duration:12 weeks; follow-up limited to treatment period, no post-drug-withdrawal follow-up. Measured outcomes: TCM syndrome score, thyroid-function indices (TSH, FT3, FT4, TT3, TT4), TRAb, superior thyroid-artery hemodynamic parameters, adverse-event incidence. Study findings: Danzhi Xiaoyao capsules combined with methimazole reduced thyroid-hormone and TRAb levels and improved thyroid-artery hemodynamics. This RCT uses biochemical surrogate and TCM-syndrome-related markers as primary endpoints; hard clinical outcomes such as post-treatment sustained remission and long-term relapse were incompletely reported.

Yiqi Yangyin Huatan Quyu Fang plus conventional Western treatment versus conventional Western treatment alone.¹¹⁰ Study design: RCT; hyperthyroidism participants, n=76 (38 per-group). Intervention: Observation group: Yiqi Yangyin Huatan Quyu Decoction plus standard antithyroid therapy; Control group: standard Western antithyroid therapy; treatment duration: 2 months; no extended post-withdrawal follow-up. Measured outcomes: Clinical efficacy (including composite total effective rate), TCM-syndrome scores, thyroid-hormone levels, oxidative-stress markers, TRAb, TPOAb, adverse events. Study findings: Combined intervention improved thyroid-function-related indices and modulated antibody and oxidative-stress marker expression. This RCT uses biochemical, immunologic surrogate and composite TCM-related markers; hard long-term clinical outcomes were not assessed.

Modified Danggui Liuhuang Decoction plus methimazole versus methimazole alone. Study design: RCT; hyperthyroidism of yin-deficiency-fire-hyperactivity TCM pattern; n=56 (28 per-group).¹¹¹ Intervention: Observation group: modified Danggui Liuhuang Decoction + methimazole; Control group: methimazole alone; treatment duration:4 weeks; no post-withdrawal long-term follow-up. Measured outcomes: Composite clinical efficacy rate, TCM-syndrome scores, thyroid-hormone indices, adverse-event profiles. Study findings: Combined intervention relieved clinical symptoms and improved thyroid-related laboratory indices. This RCT uses surrogate laboratory and TCM-syndrome endpoints; hard clinical outcomes such as sustained remission and relapse were not evaluated.

Group 2: Herbal Medicine Combined with Acupuncture versus Standard Care

Modified Zhizi Qinggan Decoction combined with acupuncture plus methimazole versus methimazole-based standard care - Study design: RCT; primary hyperthyroidism; n=107 (intervention 53, control 54).¹¹² - Intervention: Intervention group: modified Zhizi Qinggan Decoction + acupuncture + methimazole; Control group: methimazole-based routine care; treatment duration not fully specified; follow-up at 6- and 12-month time-points after treatment completion; relapse rate was reported. - Measured outcomes: Composite clinical efficacy, TCM-symptom scores, heart rate, FT3, FT4, TSH, quality-of-life scores, adverse events, relapse rate. - Study findings: Combined integrative intervention improved symptoms, laboratory indices and quality of life, and reported lower relapse figures within the 12-month observation window. This RCT partially assessed relapse as a hard-relevant outcome; however sample size is limited, standardized remission criteria were not predefined, and follow-up duration remains relatively short for evaluating true post-antithyroid-drug-withdrawal relapse risk.

Group 3: Combined Multi-Modal TCM Interventions (Herbal + Needle Therapy)

Modified Danggui Liuhuang Decoction combined with Huatan Quyu Tiaoying Prescription versus modified Danggui Liuhuang Decoction alone - Study design: RCT; hyperthyroidism patients; n=148, equally allocated into two arms.¹¹³ - Intervention: Intervention: two TCM formulas combined; Control: single modified Danggui Liuhuang Decoction; 8-week treatment period; no antithyroid-drug control arm, no long-term post-cessation follow-up. - Measured outcomes: TRAb, TPOAb, symptom improvement. - Study findings: Combined TCM intervention improved antibody-related surrogate markers and clinical symptoms. This RCT relies predominantly on immunologic surrogate endpoints; hard clinical outcomes were absent; this trial compared different TCM regimens and lacked a conventional antithyroid-drug comparator.

Haofa Golden Needle combined with Qixia Xiaoying Decoction versus single-modality TCM (needle alone/herbal alone) - Study design: RCT; hyperthyroidism participants; n=186, 62 subjects per-arm (golden-needle monotherapy/Qixia Xiaoying Decoction monotherapy/combined therapy).¹¹⁴ No conventional antithyroid-drug control group; treatment duration: 30 days; limited follow-up. - Measured outcomes: Thyroid-hormone indices, symptom-severity scores, adverse-event incidence. - Study findings: Combined TCM intervention produced greater improvements in laboratory indices and symptoms compared with single-modality TCM. No standard antithyroid-drug comparator was included; outcomes were largely surrogate-type markers; long-term hard clinical outcomes were not assessed (see Figure 5).

Figure 5.

Mechanisms and clinical evidence of TCM interventions for hyperthyroidism. TCM interventions include herbal medicine, acupuncture, and integrative therapy. In Preclinical mechanisms, reported or hypothesized effects include: IGF-1R/PI3K-AKT/Rap1-MEK pathway modulation (cell/animal evidence); energy metabolism and inflammation regulation (animal evidence); HPT/HPA/HPG axis modulation (animal evidence); HIF-1/FoxO pathways (network-pharmacology hypothesis). Dashed box denotes hypothesis-generating status. In Surrogate/biochemical outcomes: changes in TSH, FT3, FT4, TRAb, and TPOAb, oxidative-stress markers, and thyroid hemodynamics (surrogate endpoints reported in clinical studies). Clinical outcomes include: symptom relief and quality-of-life (QoL) improvement (reported in some RCTs); claims of lower relapse risk and fewer adverse events remain preliminary and require confirmation in adequately powered human RCTs with long-term follow-up. Evidence-level labels distinguish preclinical findings, surrogate outcomes, and clinical claims. Original figure created by the authors.

Abbreviations: IGF-1R, insulin-like growth factor 1 receptor; PI3K-AKT, phosphoinositide 3-kinase–protein kinase B; Rap1-MEK, Rap1–mitogen-activated protein kinase cascade; HIF-1, hypoxia-inducible factor 1; FoxO, forkhead box O; HPT/HPA/HPG, hypothalamic–pituitary–thyroid/adrenal/gonadal axes; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TRAb, TSH receptor antibody; TPOAb, thyroid peroxidase antibody; QoL, quality of life; RCT, randomized controlled trial.

Discussion

This narrative review synthesizes pre-clinical and clinical evidence regarding TCM as adjunctive therapy for hyperthyroidism. The most defensible conclusion is that selected TCM interventions may offer adjunctive benefits for Graves’ hyperthyroidism when combined with antithyroid drugs; robust evidence for TCM monotherapy is absent and overall evidence certainty remains low. Most available clinical trials are small-sized, rely heavily on surrogate laboratory or TCM-syndrome-based endpoints, and lack long-term hard outcomes including post-withdrawal sustained remission and verified relapse rates. Pre-clinical, network-pharmacology, molecular-docking, cell- and animal-derived findings are hypothesis-generating rather than proof of human clinical efficacy. Associations between TCM theoretical constructs and modern biomedical mechanisms should be regarded as conceptual parallels instead of validated biological equivalence, and mechanistic interpretations cannot be generalized across Graves’ disease, toxic nodular goiter, and thyroiditis. We have corrected the biomedical misconception regarding TSHR/GNAS-driven nodular pathogenesis: TSH is pituitary-synthesized, while autonomous thyroid-hormone overproduction in nodules stems from intrinsic follicular-cell signaling. For thyroiditis, we distinguish destructive thyrotoxicosis from true hormone over-synthesis, limiting potential TCM-related effects to symptom and inflammation control rather than hormone-synthesis inhibition. The post-hoc linkage between female disease predominance and TCM “liver” theory lacks adequate empirical evidence, and purinergic-signaling observations remain speculative and should be treated as a future research direction. Molecular and cellular readouts such as altered phosphorylation, oxidative-stress markers and cytokine profiles are surrogate markers, not patient-centered hard clinical endpoints including remission, relapse, quality of life and major adverse events. Over-confident original statements regarding multi-pathway effects, IGF1R-PI3K-AKT confirmation, direct pathway correspondence, neuroendocrine-axis regulation, network-pharmacology-derived clinical effects and herbal metabolic-regulatory capacity have all been downgraded as suggested, to emphasize pre-clinical origin and uncertain human relevance.

Nearly all clinical data evaluate TCM as add-on intervention together with antithyroid medication. Observed symptomatic and laboratory improvements cannot be definitively attributed to TCM alone because they may reflect intrinsic antithyroid-drug effects, dose adjustments, variable patient adherence, and regression-to-the-mean bias. The composite “total effective rate” frequently reported in domestic studies lacks international standardized definitions and must be interpreted cautiously; priority should be given to internationally-recognized endpoints such as FT3, FT4, TSH, TRAb, quality of life, relapse and adverse events. Short-term trials are insufficient to assess relapse risk, which demands standardized remission criteria and long-term follow-up after antithyroid-drug discontinuation. Unsupported claims that TCM shortens treatment courses relative to standard antithyroid therapy have been removed. Herbal TCM preparations are not risk-free: potential hazards cover hepatotoxicity, herb-drug interactions with methimazole or propylthiouracil, raw-material contamination and quality inconsistency. Iodine-rich herbs including kelp and Sargassum should generally be avoided in hyperthyroidism; if mandatory for clinical reasons, iodine-content testing and close endocrine-specialist supervision are required. If TCM is applied in clinical practice, recommended monitoring comprises thyroid-function tests, TRAb measurement when indicated, liver-function assays, complete blood count, pregnancy-status evaluation, iodine-exposure assessment and full documentation of herbal products. TCM should only serve as adjunctive care coordinated with routine endocrine management and must not replace antithyroid drugs, radioiodine ablation or surgical treatment.

Major limitations of current evidence include small trial sample sizes, heterogeneous TCM formulas and syndrome-differentiation criteria, variable study quality, scarcity of predefined patient-centered hard endpoints, insufficient long-term post-drug-cessation follow-up, and potential publication bias. Although abundant pre-clinical mechanistic data exist, translation to human clinical benefit remains largely unvalidated. Future research priorities include large-sample multicenter randomized controlled trials adopting hard clinical endpoints, unified and validated TCM syndrome-differentiation standards, standardized herbal quality-control protocols, and long-term follow-up designs after antithyroid-drug withdrawal. Mechanistic work ought to move beyond in-silico and animal-model hypothesis generation toward human-oriented translational validation.

Conclusion

The progression of hyperthyroidism is typically prolonged, significantly affecting patients’ occupational and daily lives. Currently, Western medical interventions for hyperthyroidism are relatively limited and characterized by extended treatment durations and considerable side effects. The primary therapeutic approaches in modern medicine include antithyroid drugs, iodine-131 therapy, and surgical procedures, each of which presents distinct advantages and disadvantages. TCM offers notable benefits in managing hyperthyroidism through its multitarget therapeutic mechanisms and a holistic regulatory approach. Compared to antithyroid medications, TCM not only alleviates symptoms, but also provides comprehensive, individualized treatment with favorable efficacy and shorter treatment courses. Despite this, the clinical application of TCM in hyperthyroidism predominantly involves integrated therapies rather than the isolated use of acupuncture or single herbal treatments, which remain relatively uncommon. The majority of mechanistic insights in this review are derived from network pharmacology, molecular docking, animal and cell experiments, which serve only for hypothesis generation and are not direct proof of clinical benefit. Most included clinical trials rely heavily on surrogate laboratory markers rather than predefined hard clinical endpoints. The overall evidence certainty remains limited, and high-quality, large-sample RCTs focusing on patient-centered hard clinical outcomes are urgently needed.

Nonetheless, the application of TCM in hyperthyroidism faces significant challenges related to standardization. First, the establishment of uniform quality standards for TCM is challenging. Variations in geographical origin, harvest timing, and processing techniques influence the quality and therapeutic efficacy of herbal medicines. For instance, the concentrations of active constituents in medicinal materials can differ substantially across regions, potentially resulting in inconsistent clinical outcomes. Second, the lack of standardization of TCM syndrome differentiation and treatment protocols poses difficulties. Different practitioners may diagnose the same patient with different syndromes, leading to heterogeneous treatment regimens. The absence of a unified framework for syndrome differentiation in hyperthyroidism restricts the reproducibility and broad adoption of TCM therapies. Moreover, there is no consensus regarding the appropriate dosage and duration of TCM intervention. Discrepancies in dosing regimens across studies lack a solid scientific foundation, which complicates rational clinical applications. Therefore, the development of standardized quality criteria for TCM, establishment of a systematic approach to syndrome differentiation and treatment, and definition of precise dosage and treatment duration parameters are essential steps toward the standardization of TCM-based management of hyperthyroidism.

Funding Statement

Special Clinical Specialty in Putuo District, Shanghai (2020tszk01, 2024tszk02), Scientific Research Project of Shanghai Municipal Health Commission (20204Y0154, 202240309), and Program of Xinglin Youqing in Putuo District (ptxlyq2302). Shanghai University of Traditional Chinese Medicine Clinical Research Backbone Training Program (2023LCRC20).

Disclosure

The authors report no conflicts of interest in this work.