The progression of TRAb-positive subacute thyroiditis and its differential diagnosis from Graves’ disease

Subacute thyroiditis (SAT) is a self-limiting thyroiditis with an unclear pathogenesis. Human leukocyte antigen (HLA)-B*35 is considered a predisposing factor, and viral infection is believed to be a trigger. In recent years, elevated levels of thyroid-stimulating hormone receptor antibodies (TRAb) have been observed in some patients with SAT. Typically, these elevated TRAb levels may spontaneously revert to negative as the disease improves. The mechanism of TRAb production may be related to abnormalities in immune surveillance and viral infections. Critically, the presence of TRAb can influence clinical manifestations, complicate diagnosis, and affect recovery in SAT. There are three types of TRAb, yet studies on their changing patterns during SAT remain scarce. Both SAT and Graves’ disease (GD) can cause thyrotoxicosis, leading to difficulties in clinical differential diagnosis, especially when SAT presents with positive TRAb. Currently, studies on TRAb-positive SAT are relatively limited. Therefore, this article reviews the pathogenesis of TRAb-positive SAT and its differential diagnosis from GD, aiming to enhance the understanding of this disease among clinicians.

1 Introduction

Subacute thyroiditis (SAT) is a common, self-limiting thyroid disorder, accounting for about 5% of all thyroid disorders (1). It occurs more often in women, especially between the ages of 30 and 50 (2). An epidemiological study from Olmsted County, Minnesota (2003) estimated its overall incidence at 4.9 cases per 100,000 person-years (3). Typical clinical manifestations include fever, neck pain, thyroid goiter, and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, during the coronavirus disease 2019 (COVID-19) pandemic, painless SAT gained attention, and neck pain is no longer considered an essential clinical manifestation (4). These nonspecific symptoms often lead to missed or incorrect diagnoses, affecting patients’ quality of life.

In recent years, the detection of high-titer thyroid-stimulating hormone receptor antibodies (TRAb) in patients with SAT has gained clinical attention (5, 6), presenting a diagnostic challenge in distinguishing it from Graves’ disease (GD). While existing reviews have summarized general SAT management (7) and some reports note TRAb in SAT cases (8, 9), a dedicated synthesis on the pathogenesis, clinical impact, and diagnostic strategy for “TRAb-positive SAT” is still lacking. To address this, this review systematically examines the mechanisms of TRAb production in SAT, evaluates its effect on disease course and prognosis, and proposes a stepwise diagnostic framework to differentiate TRAb-positive SAT from GD, aiming to offer practical guidance for clinical practice.

Note that other autoimmune thyroid disorders, such as Hashimoto’s thyroiditis, are mainly associated with thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), and follow a different clinical course from SAT. Thus, these conditions fall outside the scope of this detailed discussion.

2 The pathogenesis of TRAb-positive SAT

The pathogenesis of SAT remains unclear. Human leukocyte antigen (HLA)-B*35 is a key susceptibility factor, first reported by Nyulassy et al. in 1975 (10) and subsequently confirmed across diverse populations (11–14). Later studies also identified associations with HLA-B*18:01, -DRB1*01, and -C*04:01 (15). Beyond genetics, viral infection is a common trigger (15). The rise in SAT cases following COVID-19 suggests severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be a causative agent (16). The molecular mechanisms of SARS-CoV-2-related SAT are partly understood. After viral invasion of the thyroid, antigen-presenting cells present viral particles via major histocompatibility complex class I (MHC-I) molecules to CD8+ cytotoxic T lymphocytes (CTLs), initiating bystander killing effects (17). In contrast, SARS-CoV-2 induction of GD is less clear, though helper T cell-mediated cytotoxicity may be involved (17). A retrospective study by Korkmaz et al. (18) genotyped HLA alleles in 51 SAT patients and 190 controls, stratified by COVID-19 history. Results showed that in the COVID-19(+) group, HLA-DRB1*13:02 and HLA-DRB1*13:03 were more frequent in SAT patients. In the COVID-19 (–) group, HLA-B*35:03, HLA-DRB1*12:01, and HLA-DRB1*14:01 were elevated in SAT patients, suggesting susceptibility alleles may differ based on prior COVID-19 infection. Moreover, the haplotype of HLA-A*11-B*35-C*04 was first shown to be associated with SAT, especially after SARS-CoV-2 vaccination (19). However, a recent large-scale epidemiological study challenges existing views, refuting associations between SAT and enteroviruses (e.g., echovirus, Coxsackievirus) or other viruses including SARS-CoV-2 (20). To date, the precise etiology of SAT remains unclear, with significant controversies and research gaps.

In recent years, TRAb positivity has been observed during SAT. Its mechanism remains unclear but may involve the following aspects (Figure 1). On one hand, viral infections can damage thyroid follicular epithelial cells, potentially triggering an immune response and the production of thyroid antibodies. This may occur through molecular mimicry. Molecular mimicry refers to the phenomenon whereby self-epitopes are recognized as foreign antigens due to their structural or sequence similarity to pathogen-derived peptides (21). Evidence indicates that several peptide sequences exhibit homology between human proteins and SARS-CoV-2 viral proteins (22, 23), a similarity not observed in mammalian species unaffected by SARS-CoV-2 (22). Consequently, the adaptive immune system may generate antibodies targeting viral components, which could cross-react with structurally similar autoantigens, potentially leading to autoimmune responses (21). Several human proteins, including thyroid-derived peptides, have been identified to share sequences with SARS-CoV-2 and may thus become susceptible to cross-activation of autoreactive T and B cells by COVID-19, leading to severe autoimmunity (21). On the other hand, Sumie Fujii et al. (24) observed that thyroid tissue damage can lead to the thyroid-stimulating hormone receptor (TSHR) release into the bloodstream, where it can induce an autoimmune response to produce TRAb. Furthermore, inflammation affects the immune surveillance system, leading to autoantibody production. Inflammation and destructive changes appear to affect the degradation of TRAb. Several studies show TRAb often becomes negative as SAT resolves (24, 25), likely due to the gradual restoration of immune surveillance.

Figure 1

Figure 1. The mechanism of TRAb production in subacute thyroiditis.

Unlike SAT, elevated TRAb titers in GD require antithyroid drug (ATD) therapy. Higher TRAb titers often necessitate longer treatment duration and higher medication doses (25). Research on the mechanism of TRAb generation in TRAb-positive SAT is still limited and needs further investigation. This research is crucial, as TRAb in SAT affects the disease’s clinical course and prognosis, and complicates differential diagnosis.

3 The impact of TRAb on the course and prognosis of SAT

The clinical course of SAT typically includes three phases: the thyrotoxic phase, the hypothyroid phase, and the recovery phase. The thyrotoxic phase usually lasts three to six weeks and involves widespread thyroid follicular destruction, leading to excessive thyroid hormone release. This is subsequently followed by the hypothyroid phase, which generally resolves within six months (26). However, not all patients with SAT follow this typical course. Li Chengjiang et al. (25) reported a SAT patient with a 22−month thyrotoxic phase and no transient hypothyroidism. The patient was TRAb−positive, and this positive status persisted for 22 months before resolving spontaneously. The patient’s thyroid-stimulating hormone (TSH) levels later normalized, suggesting that persistent TRAb may be linked to a prolonged thyrotoxic phase in SAT.

Regarding the prognosis of SAT, while most patients regain normal thyroid function, recurrence occurs in about 6.9-34.8% (Table 1). The cause of recurrence is unknown but may be HLA-dependent, linked to the coexistence of HLA-B*18:01 and HLA-B*35 (27, 28). Permanent hypothyroidism develops in approximately 6-26.8% of patients, necessitating long-term thyroid hormone replacement therapy (Table 2). Previous studies have found that the occurrence of persistent hypothyroidism is related to the peak TSH level within 3 months after SAT onset, but not to the levels of ESR, CRP, thyroglobulin, or the extent of thyroiditis (29–31). Other reports find no association with age, BMI, pre-treatment TSH, or initial prednisone dose, but note a correlation with cumulative prednisone dose and female sex. A cumulative prednisone dose exceeding 4 grams is the only predictor of higher hypothyroidism risk (32). Conversely, corticosteroid therapy is highly effective in preventing permanent hypothyroidism after SAT (33).

Table 1

Table 1. Summary of recurrence rates in patients with subacute thyroiditis.

Table 2

Table 2. Summary of the incidence of patients with subacute thyroiditis developing permanent hypothyroidism.

Although the majority of patients with SAT are TRAb-negative, a subset of SAT patients exhibits TRAb-positivity. The TRAb status may influence disease prognosis. It is worth noting that even if there is a persistent positive antibody throughout the SAT process, it may progress to hypothyroidism. For example, Anu Alvin Mathew et al. (8) reported a SAT patient who, after prednisone treatment, developed hypothyroidism that required long-term levothyroxine therapy. TRAb remained elevated at 4.75 IU/L 16 months after onset (reference range: <2.0 IU/L), despite normal TPOAb. Persistently high TRAb levels may also serve as a predictor for subsequent GD, although this is rare. S. Al-Bacha et al. (9) identified 5 such cases among 31 patients, all male. The TRAb subtypes can transform during SAT, shifting thyroid function. Iitaka et al. (34) described a patient who initially developed thyroid-stimulating blocking antibody (TSBAb)-positive hypothyroidism, which later transitioned to thyroid-stimulating antibody (TSAb)-positive hyperthyroidism. At presentation, thyrotropin-binding inhibitory immunoglobulin (TBII) activity was primarily due to a high TSBAb titer (94%). Over the following months, both TBII and TSBAb titers rose, coinciding with a hypothyroid state. As these titers subsequently declined, the patient’s hypothyroidism resolved spontaneously. However, 18 months after the initial onset of SAT, the patient developed hyperthyroidism, now associated with elevated TSAb and undetectable TSBAb. Despite recognition of these changes, research on TRAb subtype dynamics in SAT remains limited.

4 Differential diagnosis of SAT and GD

SAT is an acute thyroid inflammation, typically presenting with neck pain, fever, and myalgia. In contrast, GD is an autoimmune disorder characterized by diffuse thyroid enlargement and hyperthyroidism, and may involve varying degrees of exophthalmos. GD accounts for about 85% of hyperthyroidism cases (35). The co-occurrence of SAT and GD is rare, with few cases reported (36–39). Both SAT in its thyrotoxic phase and GD can cause thyrotoxicosis with similar symptoms, making clinical differentiation difficult, especially in SAT patients without neck pain. A Japanese study found 62.1% of SAT patients were initially misdiagnosed with hyperthyroidism (40). Given their distinct causes and treatments, accurate differential diagnosis is crucial. Common diagnostic methods include TRAb measurement, radioactive iodine uptake (RAIU) testing, thyroid imaging, and thyroid ultrasonography. RAIU is considered the gold standard for distinguishing SAT from GD. However, due to its radioactivity, need for specialized equipment, and contraindications in pregnancy and lactation, it is not routinely used in clinical practice.

4.1 TRAb level

TRAb (also called TBII) includes three subtypes: TSAb, TSBAb, and neutralizing antibody. TSAb exerts biological effects similar to TSH but with stronger stimulatory activity. It competitively binds to TSHR, serving as a pathogenic autoantibody in GD. In contrast, TSBAb induces hypothyroidism by blocking TSH binding to its receptor. Neutralizing antibodies also bind specifically to TSHR, but their epitopes differ from those recognized by TSH, thus not interfering with TSH-TSHR interaction or subsequent biological responses (Figure 2). Currently, TRAb detection mainly uses receptor assays and bioassays. Receptor assays are operationally simple and rapid, including radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay. Bioassays determine subtypes by measuring cAMP levels after antibody binding. Specifically, thyroid-stimulating immunoglobulin (TSI) measures the stimulatory bioactivity of TRAb by incubating patient serum with TSHR-expressing cells and measuring cAMP production (41), with results expressed as specimen-to-reference ratio percentages (%SRR) (41). Conversely, thyroid blocking immunoglobulin (TBI) quantifies the inhibitory bioactivity of TRAb by measuring the percentage inhibition of TSH-stimulated cAMP production compared to control (41). However, bioassays are relatively cumbersome, time-consuming, costly, and technically demanding, limiting their current use primarily to research settings (42). In clinical practice, receptor assays are widely used. It is important to note that this method only indicates the presence of autoantibodies against TSHR (including TSAb and TSBAb) but does not reflect their functional status.

Figure 2

Figure 2. Biological effects and clinical significance of the TRAb subtype.

TRAb level testing is one of the quickest, easiest, and most economical methods for differential diagnosis. It shows high specificity for GD, with numerous studies reporting a positive rate over 95% in untreated GD patients (43). However, TRAb alone cannot fully differentiate between thyrotoxicosis caused by GD and SAT. Some GD patients with mild symptoms may have normal TRAb levels at initial presentation, especially early on (44). Others with minimal or stable thyroid volume may also test negative (45). Notably, elevated TRAb titers can occur during or after SAT (5, 6), with reported positivity rates ranging from 2.2% to 60.8% (Table 3). Hence, relying solely on serum TRAb positivity is insufficient to determine the cause of thyrotoxicosis.

Table 3

Table 3. Summary of TRAb positivity in patients with subacute thyroiditis.

The commonly used clinical cutoff for TRAb in differentiating GD from SAT is 1.50 IU/L (46). However, Wang Yu et al. (46) showed that an optimal cutoff of 1.05 IU/L offers higher sensitivity and accuracy: levels above this suggest GD, while levels below are more likely SAT (normal reference range: <1.75 IU/L). Lakshmi T Naga Nitin et al. (47) found that at a TRAb threshold of 2.0 IU/L in the Indian population, diagnostic sensitivity was 97.5% and specificity 100% (normal reference range: <1.75 IU/L).

Combining multiple laboratory tests may enhance diagnostic performance compared to single tests. Ma Haimei et al. (5) found that in patients with thyrotoxicosis, an FT4/FT3 ratio ≥ 2.8 suggests the possibility of SAT, while a ratio < 2.8 points to GD. The combined detection of FT4/FT3 and TRAb demonstrated higher sensitivity and specificity in distinguishing between GD and SAT, both of which significantly exceeded those of individual tests. These results are significantly better than individual tests, indicating the potential value of promoting this combined testing method. Cai Mei et al. (48) found TPOAb and TRAb useful in distinguishing SAT from GD. Specifically, concurrent elevation of both antibodies and TRAb measured value/reference value higher than 3, may serve as distinguishing features between the thyrotoxic phase in SAT and GD.

However, most existing studies have small sample sizes and are single−center, which may introduce bias. Future large−scale, multicenter epidemiological studies are needed to validate these findings and strengthen their reliability.

4.2 Thyroid iodine uptake rate

RAIU measurement is another important test for identifying the cause of thyrotoxicosis. In most SAT patients, thyroid iodine uptake decreases due to follicular epithelial disruption, elevated serum thyroid hormone levels, and suppressed TSH. This creates the characteristic dissociation between high serum thyroid hormone levels and low thyroid iodine uptake. However, in some TRAb-positive SAT patients, TRAb stimulates TSH receptors on residual follicular cells, causing these remaining tissues to become hyperfunction or hypofunctional, thereby altering iodine uptake patterns.

Sumie Fujii et al. (24) reported a SAT case with high TRAb and TSAb levels and elevated RAIU, observed after CRP, ESR, FT4, and FT3 had normalized following prednisolone treatment. Shigenori Nakamura et al. (49) documented a SAT patient with both TSAb and TSBAb. During the thyrotoxic phase, despite TSH suppression, RAIU remained elevated at 35.5%. At this stage, TSAb was positive while TSBAb was negative, indicating that thyroid hormone production resulted from both destructive thyroiditis and TSAb-mediated stimulation. Three months later, when RAIU decreased to 20.7% with persistent TSH suppression, TSAb turned negative and TSBAb became positive. Five months after initial presentation, RAIU increased to 31.1%, TSH normalized, TSBAb reverted to negative, and TSAb reappeared.

These findings suggest that RAIU fluctuations in SAT may reflect the dynamic presence of TSAb. As a result, single RAIU measurements have limitations in accurately diagnosing and interpreting SAT pathophysiology.

4.3 Thyroid radionuclide imaging and color Doppler ultrasound

Thyroid radionuclide imaging uses technetium-99m (99mTc) to visualize the thyroid gland. It provides information on thyroid size, location, shape, structure, and both overall and regional function. The procedure involves radiation exposure and should not be repeated frequently. It is contraindicated during pregnancy and lactation, and is not useful after recent high iodine intake.

In the thyrotoxic phase of SAT, 99mTc uptake is typically low due to destruction of follicular epithelial cells, hormone release, and suppressed TSH. However, TRAb presence can lead to normal or elevated uptake in some SAT patients (25). A recent study proposed a 99mTc−pertechnetate uptake cutoff of 1.1% to distinguish GD from SAT, with 97% sensitivity and 95% specificity, but the study was limited by small sample size and single−center design. The influence of iodine intake on this test’s accuracy remains unclear (50).

Doppler ultrasound is a non−invasive method for assessing thyroid blood flow (TBF). Hisashi Ota et al. (51) demonstrated that energy Doppler ultrasound can quantify both thyroid volume and TBF, revealing TBF values exceeding 4% in all GD patients, while values in painless thyroiditis and SAT patients remained consistently below 4%. Moreover, Sajad Ahmad Malik et al. (52) reported that the peak systolic velocity of the inferior thyroid artery (PSV-ITA), measured via color Doppler ultrasound, achieved 91% sensitivity and 89% specificity in differentiating GD from thyroiditis when using an average cutoff value of 30 cm/s. These diagnostic performance metrics are comparable to those of the 99mTc-pertechnetate thyroid uptake scan. Thus, PSV−ITA measurement is particularly useful in pregnancy, lactation, after iodine exposure, or where nuclear medicine is unavailable.

Given these diagnostic options, a systematic approach can enhance clinical efficiency. We therefore propose a step-by-step integrated diagnostic algorithm to facilitate accurate and timely distinction between SAT and GD. First, evaluate clinical features and neck ultrasound for typical SAT characteristics such as pain, fever, and patchy hypoechoic areas with reduced flow. If uncertainty remains, second-line tools like the FT3/FT4 ratio and PSV-ITA can aid discrimination. As a third step, thyroid RAIU may be employed, though results should be interpreted cautiously since TRAb-positive SAT can show atypical (normal or elevated) uptake patterns. Diagnosis should integrate all clinical, sonographic, and laboratory findings rather than relying on any single test. Final confirmation comes from monitoring TRAb titer dynamics during follow-up. This protocol translates current evidence into a practical pathway to improve diagnostic accuracy.

5 Limitations and future directions

The current research still has the following limitations: Firstly, the generation mechanism of TRAb is still speculative and lacks direct experimental evidence; Secondly, the impact of TRAb on the long-term prognosis of SAT remains undetermined due to inconsistent data. The most crucial point is that there is currently no standardized diagnostic process that integrates these multi-dimensional parameters. Future research should prioritize large-scale longitudinal studies to clarify the natural history of TRAB-positive SAT and formulate optimized diagnosis and treatment strategies.

6 Conclusions

This review confirms that TRAb positive is a clinical variant type of concern in SAT, and its occurrence may be related to immune exposure after thyroid destruction and can prolong the course of thyrotoxicosis. This type of situation overlaps with the clinical manifestations of GD, making differentiation difficult. To this end, we offer a stepwise integrated diagnostic strategy to enhance the accuracy and clinical practicality of differential diagnosis.

Author contributions

SY: Data curation, Visualization, Writing – original draft. XZ: Investigation, Writing – review & editing. FL: Data curation, Writing – review & editing. JY: Conceptualization, Writing – review & editing. JZ: Funding acquisition, Investigation, Software, Writing – review & editing.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the National Natural Science Foundation of China (grant number 82303031), Shandong Provincial Natural Science Foundation of China Grants (grant number ZR2019PH025), Projects of medical and health technology development program in Shandong province (grant number 2016WS0499), Bethune Public Welfare Foundation (grant number Z04JKM2022E036), and Scientific Research Nurturing Fund of the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital (grant number QYPY2023NSFC0601).

Acknowledgments

On the occasion of the completion of the thesis, I would like to express my heartfelt thanks to all the people and funds who have given me help and support. First of all, I would like to thank my tutor Professor Zhao Junyu for his careful guidance and help in the selection, writing and revision of this paper. I would also like to thank the above funds for providing financial assistance during the writing of the paper. In addition, I would like to thank my colleagues for their support and encouragement in the process of writing the paper. It is with your help and support that I can finish this paper successfully. I would like to express my sincere thanks!

Conflict of interest

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

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Abbreviation

SAT, Subacute thyroiditis; HLA, human leukocyte antigen; TRAb, thyroid-stimulating hormone receptor antibody; GD, Graves’ disease; TPOAb, thyroid peroxidase antibodies; TgAb, thyroglobulin antibodies; ESR, erythrocyte sedimentation rate; CRP, C-reaction protein; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; MHC-I, major histocompatibility complex class I; CTLs, cytotoxic T lymphocytes; TSHR, thyroid-stimulating hormone receptor; ATD, antithyroid drug; TSH, thyroid-stimulating hormone; TSBAb, thyroid-stimulating blocking antibody; TSAb, thyroid-stimulating antibody; TBII, thyrotropin-binding inhibitory immunoglobulin; RAIU, radioactive iodine uptake; ELISA, enzyme-linked immunosorbent assay; cAMP, cyclic adenosine monophosphate; TSI, Thyroid-stimulating immunoglobulin; %SRR, %specimen-to-reference ratio percentages; TBI, Thyroid blocking immunoglobulin; 99mTc, technetium-99m; TBF, thyroid blood flow; PSV-ITA, peak systolic velocity of the inferior thyroid artery.

References

1. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. (2011) 17:456–520. doi: 10.4158/ep.17.3.456

PubMed Abstract | Crossref Full Text | Google Scholar

2. Engkakul P, Mahachoklertwattana P, and Poomthavorn P. Eponym : de Quervain thyroiditis. Eur J Pediatr. (2011) 170:427–31. doi: 10.1007/s00431-010-1306-4

PubMed Abstract | Crossref Full Text | Google Scholar

3. Fatourechi V, Aniszewski JP, Fatourechi GZE, Atkinson EJ, and Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. (2003) 88:2100–5. doi: 10.1210/jc.2002-021799

PubMed Abstract | Crossref Full Text | Google Scholar

4. Dolkar T, Jitidhar F, Patel MJ, Hamad AM, Salauddin F, Shiferaw-Deribe Z, et al. Painless subacute thyroiditis in a patient with acute COVID-19 infection: A transient event. Cureus. (2022) 14:e26924. doi: 10.7759/cureus.26924

PubMed Abstract | Crossref Full Text | Google Scholar

5. Ma H and Tu X. Diagnostic value of free thyroxine/free triiodothyronine ratio combined with thyroid hormone antibody for subacute thyroiditis and Graves’ disease. Chin J Clin Pathol. (2023) 15:60–3. doi: 10.3969/j.issn.1674-7151.2023.01.016

Crossref Full Text | Google Scholar

6. Xie X, Liang J, and Mo C. Application value of thyroid-stimulating hormone receptor antibody in the diagnosis of toxic diffuse goiter disease. China Mod Med. (2021) 28:187–9. doi: 10.3969/j.issn.1674-4721.2021.20.054

Crossref Full Text | Google Scholar

7. Li Y, Hu Y, Zhang Y, Cheng K, Zhang C, and Wang J. Advances in subacute thyroiditis: Pathogenesis, diagnosis, and therapies. FASEB J: Off Publ Fed Am Soc Exp Biol. (2025) 39:e70525. doi: 10.1096/fj.202403264R

PubMed Abstract | Crossref Full Text | Google Scholar

8. Alvin Mathew A, Papaly R, Maliakal A, Chandra L, and Antony MA. Elevated graves’ disease-specific thyroid-stimulating immunoglobulin and thyroid stimulating hormone receptor antibody in a patient with subacute thyroiditis. Cureus. (2021) 13:e19448. doi: 10.7759/cureus.19448

PubMed Abstract | Crossref Full Text | Google Scholar

9. Al-Bacha S and Lahiri SW. Graves disease following subacute thyroiditis in a chinese man. AACE Clin Case Rep. (2022) 8:73–7. doi: 10.1016/j.aace.2021.10.001

PubMed Abstract | Crossref Full Text | Google Scholar

10. Nyulassy S, Hnilica P, and Stefanovic J. The HL-a system and subacute thyroiditis. A preliminary report. Tissue Antigens. (1975) 6:105–6. doi: 10.1111/j.1399-0039.1975.tb00622.x

PubMed Abstract | Crossref Full Text | Google Scholar

11. Zein EF, Karaa SE, and Megarbane A. Familial occurrence of painful subacute thyroiditis associated with human leukocyte antigen-B35. Press Med. (2007) 36:808–9. doi: 10.1016/j.lpm.2007.02.011

PubMed Abstract | Crossref Full Text | Google Scholar

12. Hamaguchi E, Nishimura Y, Kaneko S, and Takamura T. Subacute thyroiditis developed in identical twins two years apart. Endocr J. (2005) 52:559–62. doi: 10.1507/endocrj.52.559

PubMed Abstract | Crossref Full Text | Google Scholar

13. Kramer AB, Roozendaal C, and Dullaart RPF. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35. Thyroid: Off J Am Thyroid Assoc. (2004) 14:544–7. doi: 10.1089/1050725041517048

PubMed Abstract | Crossref Full Text | Google Scholar

14. Korkmaz FN, Gökçay Canpolat A, Dalva K, Elhan AH, Şahin M, Çorapçıoğlu D, et al. Determination of the relationship between the development and recurrence of subacute thyroiditis and human leukocyte antigen subtypes. Genet Test Mol Biomarkers. (2024) 28:2–9. doi: 10.1089/gtmb.2023.0386

PubMed Abstract | Crossref Full Text | Google Scholar

15. Stasiak M and Lewiński A. New aspects in the pathogenesis and management of subacute thyroiditis. Rev Endocr Metab Disord. (2021) 22:1027–39. doi: 10.1007/s11154-021-09648-y

PubMed Abstract | Crossref Full Text | Google Scholar

16. Speer G and Somogyi P. Thyroid complications of SARS and coronavirus disease 2019 (COVID-19). Endocr J. (2021) 68:129–36. doi: 10.1507/endocrj.EJ20-0443

PubMed Abstract | Crossref Full Text | Google Scholar

17. Mohammadi B, Dua K, Saghafi M, Singh SK, Heydarifard Z, and Zandi M. COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms. J Med Virol. (2023) 95:e29001. doi: 10.1002/jmv.29001

PubMed Abstract | Crossref Full Text | Google Scholar

18. Korkmaz FN, Gökçay Canpolat A, Dalva K, Şahin M, Çorapçıoğlu D, and Demir Ö. Common human leucocyte antigens associated with the development of subacute thyroiditis and COVID-19. Hum Immunol. (2024) 85:110834. doi: 10.1016/j.humimm.2024.110834

PubMed Abstract | Crossref Full Text | Google Scholar

19. Sahin Tekin M, Yorulmaz G, Yantir E, Gunduz E, and Colak E. A novel finding of an HLA allele’s and a haplotype’s relationship with SARS-CoV-2 vaccine-associated subacute thyroiditis. Vaccines. (2022) 10:1986. doi: 10.3390/vaccines10121986

PubMed Abstract | Crossref Full Text | Google Scholar

20. Orth HM, Killer A, Gliga S, Böhm M, Feldt T, Jensen B-EO, et al. Subacute thyroiditis-is it really linked to viral infection? J Clin Endocrinol Metab. (2025) 110:2938–45. doi: 10.1210/clinem/dgaf023

PubMed Abstract | Crossref Full Text | Google Scholar

21. Fallahi P, Elia G, Ragusa F, Paparo SR, Patrizio A, Balestri E, et al. Thyroid autoimmunity and SARS-CoV-2 infection. J Clin Med. (2023) 12:6365. doi: 10.3390/jcm12196365

PubMed Abstract | Crossref Full Text | Google Scholar

22. Kanduc D and Shoenfeld Y. Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: Implications for the vaccine. Immunol Res. (2020) 68:310–3. doi: 10.1007/s12026-020-09152-6

PubMed Abstract | Crossref Full Text | Google Scholar

23. Vojdani A, Vojdani E, and Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Front Immunol. (2020) 11:617089. doi: 10.3389/fimmu.2020.617089

PubMed Abstract | Crossref Full Text | Google Scholar

24. Fujii S, Miwa U, Seta T, Ohoka T, and Mizukami Y. Subacute thyroiditis with highly positive thyrotropin receptor antibodies and high thyroidal radioactive iodine uptake. Intern Med (Tokyo Jpn). (2003) 42:704–9. doi: 10.2169/internalmedicine.42.704

PubMed Abstract | Crossref Full Text | Google Scholar

25. Zhang Z and Li C. Follow-up of a case of subacute thyroiditis with uncommon thyroid (99m)tc uptake. Arq Bras Endocrinol Meta. (2013) 57:659–62. doi: 10.1590/s0004-27302013000800013

PubMed Abstract | Crossref Full Text | Google Scholar

26. He P, Yang H, Lai Q, Kuang Y, Huang Z, Liang X, et al. The diagnostic value of blood cell-derived indexes in subacute thyroiditis patients with thyrotoxicosis: A retrospective study. Ann Transl Med. (2022) 10:322. doi: 10.21037/atm-22-719

PubMed Abstract | Crossref Full Text | Google Scholar

27. Stasiak M, Tymoniuk B, Stasiak B, and Lewiński A. The risk of recurrence of subacute thyroiditis is HLA-dependent. Int J Mol Sci. (2019) 20:1089. doi: 10.3390/ijms20051089

PubMed Abstract | Crossref Full Text | Google Scholar

28. Zhang J, Ding G, Li J, Li X, Ding L, Li X, et al. Risk factors for subacute thyroiditis recurrence: a systematic review and meta-analysis of cohort studies. Front Endocrinol. (2021) 12:783439. doi: 10.3389/fendo.2021.783439

PubMed Abstract | Crossref Full Text | Google Scholar

29. Zhao N, Wang S, Cui X-J, Huang M-S, Wang S-W, Li Y-G, et al. Two-years prospective follow-up study of subacute thyroiditis. Front Endocrinol. (2020) 11:47. doi: 10.3389/fendo.2020.00047

PubMed Abstract | Crossref Full Text | Google Scholar

30. Saklamaz A. Is there a drug effect on the development of permanent hypothyroidism in subacute thyroiditis? Acta Endocrinol. (2017) 13:119–23. doi: 10.4183/aeb.2017.119

PubMed Abstract | Crossref Full Text | Google Scholar

31. Sencar ME, Calapkulu M, Sakiz D, Akhanli P, Hepsen S, Duger H, et al. The contribution of ultrasonographic findings to the prognosis of subacute thyroiditis. Arch Endocrinol Metab. (2020) 64:306–11. doi: 10.20945/2359-3997000000253

PubMed Abstract | Crossref Full Text | Google Scholar

32. Görges J, Ulrich J, Keck C, Müller-Wieland D, Diederich S, and Janssen OE. Long-term outcome of subacute thyroiditis. Exp Clin Endocrinol Diabetes: Off J Ger Soc Endocrinol [and] Ger Diabetes Assoc. (2020) 128:703–8. doi: 10.1055/a-0998-8035

PubMed Abstract | Crossref Full Text | Google Scholar

33. Gokkaya N and Aydin Tezcan K. The effects of corticosteroid and nonsteroid anti-inflammatory therapies on permanent hypothyroidism occurring after the subacute thyroiditis. Endocr Res. (2024) 49:137–44. doi: 10.1080/07435800.2024.2344719

PubMed Abstract | Crossref Full Text | Google Scholar

34. Iitaka M, Kakinuma S, Yamanaka K, Fujimaki S, Oosuga I, Wada S, et al. Induction of autoimmune hypothyroidism and subsequent hyperthyroidism by TSH receptor antibodies following subacute thyroiditis: a case report. Endocr J. (2001) 48:139–42. doi: 10.1507/endocrj.48.139

PubMed Abstract | Crossref Full Text | Google Scholar

35. Lu N, Ran X, Li Y, and Yang Y. Research on the application value of thyroglobulin and free thyroxine/free triiodothyronine combined with thyroid hormone antibody in the diagnosis of subacute thyroiditis. Chin Gen Pract. (2019) 22:361–5. doi: 10.12114/j.issn.1007-9572.2018.00.096

Crossref Full Text | Google Scholar

36. Hoang TD, Mai VQ, Clyde PW, and Shakir MKM. Simultaneous occurrence of subacute thyroiditis and graves’ disease. Thyroid: Off J Am Thyroid Assoc. (2011) 21:1397–400. doi: 10.1089/thy.2011.0254

PubMed Abstract | Crossref Full Text | Google Scholar

37. Li L, Sun L, Yu S, and Ma C. Increased pertechnetate and radioiodine uptake in the thyroid gland with subacute thyroiditis and concurrent graves’ disease. Hell J Nucl Med. (2016) 19:49–52. doi: 10.1967/s002449910338

PubMed Abstract | Crossref Full Text | Google Scholar

38. Kageyama K, Kinoshita N, and Daimon M. A case of thyrotoxicosis due to simultaneous occurrence of subacute thyroiditis and graves’ disease. Case Rep Endocrinol. (2018) 2018:3210317. doi: 10.1155/2018/3210317

PubMed Abstract | Crossref Full Text | Google Scholar

39. Nham E, Song E, Hyun H, Seong H, Yoon JG, Noh JY, et al. Concurrent subacute thyroiditis and graves’ disease after COVID-19: A case report. J Kor Med Sci. (2023) 38:e134. doi: 10.3346/jkms.2023.38.e134

PubMed Abstract | Crossref Full Text | Google Scholar

40. Nishihara E, Ohye H, Amino N, Takata K, Arishima T, Kudo T, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med (Tokyo Jpn). (2008) 47:725–9. doi: 10.2169/internalmedicine.47.0740

PubMed Abstract | Crossref Full Text | Google Scholar

41. Morgenthaler NG, Ho SC, and Minich WB. Stimulating and blocking thyroid-stimulating hormone (TSH) receptor autoantibodies from patients with graves’ disease and autoimmune hypothyroidism have very similar concentration, TSH receptor affinity, and binding sites. J Clin Endocrinol Metab. (2007) 92:1058–65. doi: 10.1210/jc.2006-2213

PubMed Abstract | Crossref Full Text | Google Scholar

42. Wu N, Lv Z, Du J, Yang G, Ba J, Dou J, et al. Diagnostic value of thyroid-stimulating hormone receptor antibodies in Graves’ disease. Med J Chin Peopl Liber Army. (2011) 36:501–4.

Google Scholar

43. Zhu L, Zhang C, Sun X, and Huang G. ROC curve method to evaluate the significance of TRAb, TPO-Ab and TGA in the differential diagnosis of Graves’ disease and HT. J Radioimmunol. (2011) 24:564–7. doi: 10.3969/j.issn.1008-9810.2011.05.053

Crossref Full Text | Google Scholar

44. Nyström HF, Jansson S, and Berg G. Incidence rate and clinical features of hyperthyroidism in a long-term iodine sufficient area of Sweden (Gothenburg) 2003-2005. Clin Endocrinol. (2013) 78:768–76. doi: 10.1111/cen.12060

PubMed Abstract | Crossref Full Text | Google Scholar

45. Guo J, Wang Q, Sang Z, Zhang F, and Jia Q. Study on the relationship between thyroid volume and autoantibodies in patients with autoimmune thyroid disease. Chin J Endemiol. (2021) 40:845–8. doi: 10.3760/cma.j.cn231583-20201217-00334

Crossref Full Text | Google Scholar

46. Wang Y and Xie P. Study on the optimal cut-off value of TRAb in the etiological diagnosis of patients with thyrotoxicosis for the first time. Label Immunoassay Clin Med. (2022) 29:1344–7. doi: 10.11748/bjmy.issn.1006-1703.2022.08.018

Crossref Full Text | Google Scholar

47. Naga Nitin LT, Lakkundi S, S L SR, Shanthaiah DM, Datta SG, Annavarapu U, et al. High diagnostic accuracy of thyroid-stimulating hormone (TSH) receptor antibodies in distinguishing graves’ disease and subacute thyrotoxicosis in the Indian population. Cureus. (2024) 16:e54303. doi: 10.7759/cureus.54303

PubMed Abstract | Crossref Full Text | Google Scholar

48. Cai M and Guo H. Significance of serum TpoAb and TRAb detection in the differential diagnosis of subacute thyroiditis and Graves’ disease. Shandong Med J. (2013) 53:62–3. doi: 10.3969/j.issn.1002-266X.2013.39.024

Crossref Full Text | Google Scholar

49. Nakamura S, Hattori J, Ishiyama-Takuno M, Shima H, Matsui I, and Sakata S. Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb). Endocrinol Jpn. (1992) 39:469–76. doi: 10.1507/endocrj1954.39.469

PubMed Abstract | Crossref Full Text | Google Scholar

50. Gholami A, Sabbaghi M, Shirafkan H, and Mousavie Anijdan SH. 99mTc-pertechnetate cut-off to distinguish graves’ disease from subacute thyroiditis. Casp J Intern Med. (2025) 16:513–8. doi: 10.22088/cjim.16.3.513

PubMed Abstract | Crossref Full Text | Google Scholar

51. Ota H, Amino N, Morita S, Kobayashi K, Kubota S, Fukata S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from graves’ disease. Clin Endocrinol. (2007) 67:41–5. doi: 10.1111/j.1365-2265.2007.02832.x

PubMed Abstract | Crossref Full Text | Google Scholar

52. Malik SA, Choh NA, Misgar RA, Khan SH, Shah ZA, Rather TA, et al. Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating graves’ disease from thyroiditis. Arch Endocrinol Metab. (2019) 63:495–500. doi: 10.20945/2359-3997000000165

PubMed Abstract | Crossref Full Text | Google Scholar