The diagnosis and treatment of hyperthyroidism: a bibliometric analysis from 2004 to 2024

Introduction

Hyperthyroidism affects approximately 2.5% of the global population (1). When hyperthyroidism is clinically suspected, its diagnosis should be confirmed through biochemical tests, with indications including low thyrotropin (TSH), elevated free thyroxine (FT4), or highly elevated free triiodothyronine (FT3). Following biochemical confirmation, an etiological diagnosis is essential to determining the underlying cause via techniques such as TSH receptor (TSHR) antibody assays, thyroid peroxidase antibody assays, thyroid ultrasound, and nuclear imaging. Hyperthyroidism, characterized by excessive synthesis and secretion of thyroid hormones, is most commonly associated with Graves’ disease or toxic nodular goiter (2-4).

Treatment options for hyperthyroidism include antithyroid medications, radioiodine therapy (I-131), and surgery, which are widely considered first-line therapies. Additionally, emerging modalities such as immunotherapy and thermal ablation have been developed and extensively evaluated in systematic reviews and meta-analyses (5-11). Despite significant advancements in diagnostic and therapeutic strategies and the rapid proliferation of published literature, there remains a paucity of comprehensive information regarding the volume of relevant publications, contributing journals, institutions, and countries/regions.

Bibliometrics is a discipline that employs objective mathematical and statistical methods to conduct extensive, transparent, and reproducible analyses of communication media (12,13). It provides a clear depiction of the historical development and evolution of a field through time-series analysis and citation network analysis. Bibliometrics also objectively evaluates the quality and impact of studies within a field using quantitative indicators, such as impact factor, offering valuable insights for researchers and decision-makers. By identifying and analyzing frequently cited literature, bibliometrics facilitates the rapid identification of key research findings and breakthroughs within a specific area.

The aim of this study was to apply bibliometric methods to systematically characterize the development history, current research landscape, and future directions in the diagnosis and treatment of hyperthyroidism. We present this article in accordance with the BIBLIO reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-228/rc).

Methods

Relevant literature published from September 1, 2004 to September 1, 2024 was retrieved from the Web of Science Core Collection (WOSCC) database. Medical subject headings (MeSH) from the National Library of Medicine were used for topic entry. A comprehensive literature search was conducted on September 1, 2024, and all relevant documents were downloaded. The search formula employed was as follows: (((TS=(hyperthyroidism)) AND TS=(diagnosis))) OR ((TS=(hyperthyroidism)) AND TS=(treatment))) OR ((TS=(hyperthyroidism)) AND TS=(therapy)). The document types included 5,089 articles and 952 reviews, with the language restricted to English but no other search constraints being applied (see Figure 1).

Figure 1 Flowchart of the publication screening process.

Statistical analysis

Statistical analysis and data visualization were performed using VOSviewer (version 1.6.16) and CiteSpace (version 6.3.R1). We visualized data related to countries/regions and institutions, journal and journal cocitation analyses, author and author cocitation analyses, literature cocitation analyses, and keyword co-occurrence analyses. Additionally, we generated overlay maps for journals and performed citation burst analysis for both literature and keywords.

Results

Publication characteristics

A total of 6,041 publications on the diagnosis and treatment of hyperthyroidism were retrieved, comprising 5,086 articles and 953 reviews. Python was used to generate compound statistical charts to depict the annual number of publications and trends (Figure 2). Over the past 20 years, the number of articles published in the field increased substantially, rising from 50 in 2004 to 418 in 2023.

Figure 2 Annual publications and percentage of total publications in hyperthyroidism diagnosis and treatment research published from 2004 to 2024.

Most productive countries/regions, institutions, and journals

The identified articles originated from 629 countries/regions, with the top three countries/regions being the United States (n=1,235), China (n=804), and Italy (n=565), which collectively accounted for 43.11% of all publications. The top 10 countries/regions contributed 75.83% of the publications (see Table 1). To visualize the patterns of international collaboration, a cooperation network diagram was constructed based on publication volumes and interactions between countries/regions (Figure 3). Notable collaborations included those between the United States and China, as well as between China and Italy.

Figure 3 Countries’/regions’ contribution to the field of the diagnosis and treatment of hyperthyroidism. (A) Visualization of countries/regions in the field. (B) The international collaboration between countries/regions.

A total of 18,414 institutions were involved in research on the diagnosis and treatment of hyperthyroidism. Table 1 lists the 10 most productive institutions. The top three institutions were the University of Pisa (n=105), the University of California (n=103), and Harvard University (n=98). Among the top 10 institutions, three are based in the United States, three in France, and one each in Denmark, the United Kingdom, Italy, and the Netherlands. The collaborative networks between institutions highlighted significant interactions. Figure 4 presents a diagram of the interinstitutional cooperation network. The nodes and associations between nodes in this graph are represented by curved connections. Each node is presented as a yearly wheel graph, representing a keyword, and the larger the node yearly wheel circle, the more frequently the word appears. The node year wheel passes from inside to outside, the time goes from far to near, and the color tone goes from cold to warm. The connecting line between each node indicates the co-occurrence relationship between different keywords; the greater the number of connecting lines, the greater the probability of different keywords appearing in the same document.

Figure 4 Visualization of institutions on the diagnosis and treatment of hyperthyroidism research.

The literature included in the analysis was distributed across 1,438 journals. Table 2 lists the top 10 journals by publication volume, with each publishing more than 80 articles. The top three journals—Thyroid, The Journal of Clinical Endocrinology and Metabolism, and Clinical Endocrinology—each published more than 150 articles, collectively accounting for 658 documents or 10.89% of the entire corpus. Among all journals, Thyroid had the highest output (n=288, 4.77%) and impact factor (IF) (IF =5.8), followed by The Journal of Clinical Endocrinology and Metabolism (n=210, 3.48%, IF =5.0). Thirteen journals were cited more than 1,000 times. Notably, The Journal of Clinical Endocrinology and Metabolism had the highest number of citations (n=4,223), followed by Thyroid (n=3,958) and Clinical Endocrinology (n=3,130) (Table 3).

Author and author cocitation analyses

A total of 28,157 scholars contributed to research on the diagnosis and treatment of hyperthyroidism. Table 4 lists the top 10 authors based on the number of publications. Lazlo, Hegedüs ranked first with 38 publications, followed by Ruchala, Marek with 26 publications. Notably, all of the top 10 authors published more than 15 articles, with the top 5 authors each publishing over 20 articles. In the author co-occurrence analysis mapping shown in Figure 5A, the node size indicates the number of author publications, the connecting lines between the nodes represent the cooperation between authors, and the thickness of the connecting lines indicates the strength author cooperation. Meanwhile, Figure 5B illustrates the author collaboration.

Figure 5 Authors’ contribution in the field of diagnosis and treatment of hyperthyroidism. (A) Visualization of authors in the field. (B) Author co-occurrence network. (C) Visualization of author cocitations.

Among the cocited authors, the top 7 received more than 500 citations (Figure 5C and Table 4). David S. Cooper (n=861) was the most frequently cited author, followed by Douglas S. Ross (n=778) and Luigi Bartalena (n=682). Interestingly, Luigi Bartalena, George J. Kahaly, David S. Cooper and Peter Laurberg were the only four authors who ranked in the top 10 for both publications and citations.

Reference cocitation analysis

Table 5 lists the top 10 articles in terms of cocitations, with each being cited at least 100 times. Notably, five of these articles were published in Thyroid. Among all the cited articles, that by Ross et al., published in Thyroid and titled “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis” (14), was the most cited (n=358). It was closely followed by the article “2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism” (15), published in European Thyroid Journal (n=204). In addition, visual analysis of the cocited references revealed active citation relationships between them (see Figure 6).

Figure 6 Visualization of the cocited studies on the diagnosis and treatment of hyperthyroidism.

Occurrence frequency and citation burst of keywords

Table 6 lists the 10 most frequently used keywords in this field. “Hyperthyroidism”, “Graves’ disease”, and “management” occupied the top three positions, each occurring more than 1,000 times, with “hyperthyroidism” and “Graves’ disease” appearing over 1,500 times. The top 15 keywords, each with more than 300 occurrences, and the top 30 keywords, each with at least 180 occurrences, represent the principal research directions in the diagnosis and treatment of hyperthyroidism. Burst cited keywords are keywords that appear with a high frequency in a specific domain over a specific period of time. Figure 7A illustrates the keywords with the strongest citation bursts. The blue lines indicate time intervals, while the red lines indicate the periods of frequent citations. We selected the top 25 keywords with citation bursts extending through 2024. A network graph of keywords revealed research hotspots within specific fields (Figure 7B). Among them, “guidelines” (strength =51.13), “diagnosis” (strength =25.5), “case report” (strength =15.57), “meta-analysis” (strength =14.19), and “association guidelines” (strength =14.19) occupied the top five positions in terms of burst intensity. Additionally, a cluster analysis of the keywords yielded eight clusters, as shown in Figure 7C. In the figure, the eight clusters with the most nodes selected were Graves’ disease, subclinical hyperthyroidism, hypothyroidism, thyroid hormone, thyroid cancer, Graves’ orbitopathy (GO), diagnosis, and immune checkpoint inhibitors. The higher the cluster is ranked, the greater the number of articles involved is in the cluster and the larger the cluster size is. These eight clusters indicate that the literature on the diagnosis and treatment of hyperthyroidism focuses on the treatment and complications of graves, emerging immunotherapies for hyperthyroidism, and exploration of the management of hyperthyroidism treatment.

Figure 7 Research hotspots in diagnosis and treatment of hyperthyroidism. (A) Top 25 keywords with the strongest citation bursts; (B) visualization of keywords in the field; (C) keywords clusters.

Discussion

This bibliometric study analyzed the progress of research on the diagnosis and treatment of hyperthyroidism from 2004 to 2024. Research in this field has shown a steady increase over the past 20 years, with the highest number of publications recorded in 2021. The major contributing countries/regions to this field were the United States, China, and Italy. Countries/regions with a higher number of publications also tended to have more active institutions. The United States is home to five of the most productive institutions, and notably, most of the publishers of the 10 most active journals are based in the United States, with no journals from Asia among the top contributors.

The average prevalence of hyperthyroidism in Europe is 0.75% (19). However, there are few epidemiological reports on hyperthyroidism in Asia as a whole. More attention should be given to epidemiological investigations of thyroid dysfunction and iodine status, particularly in iodine-deficient developing countries/regions. In the field of diagnosis and treatment of hyperthyroidism, collaboration among authors is primarily intranational, with limited international cooperation. Increased international collaboration in the future may contribute to higher-quality studies.

Notably, “guidelines” and “diagnosis” were among the most recent and frequently occurring keywords in the literature. Guidelines on hyperthyroidism have remained a consistently common and emergent topic. Since 2011, when the American Thyroid Association (ATA) published guidelines for the management of hyperthyroidism and other causes of thyrotoxicosis, the focus on these guidelines has grown (22). In 2016, the ATA updated these guidelines (14), expanding the application of TSHR antibody testing as compared to the 2011 edition. The 2016 guidelines also included updates on hepatotoxicity and the safety of long-term use of antithyroid drugs (ATDs), revised recommendations for managing Graves’ disease in preconception and during pregnancy, and an emphasis on optimizing calcium and vitamin D metabolism prior to thyroid surgery (14).

The 2018 European Thyroid Association (ETA) guidelines on GO specifically address the treatment of hyperthyroidism in patients with GO (15). In contrast, the 2016 ETA/European Group on GO (EUGOGO) guidelines offer a more comprehensive approach to managing GO (24). The 2021 EUGOGO guidelines further refine the pharmacological treatment of GO, with a greater emphasis on precision treatment for patients with moderate-to-severe, active GO (25). These guidelines advocate for early identification of patients with more severe disease, early use of higher doses of intravenous glucocorticosteroids, and highlight the efficacy of immunosuppressants such as teprotumumab, tocilizumab, and rituximab in the treatment of GO.

The visualization network was broadly divided into eight clusters based on co-occurrence cluster analysis. Figure 5 illustrates that Graves’ disease emerged as a prominent topic in recent years, identifying it is a central focus in the field of hyperthyroidism. Due to the high incidence of complications and the complexity of clinical management associated with Graves’ disease, the literature has increasingly concentrated on its complications and treatment strategies (25-34).

Graves’ disease is an autoimmune disorder in which the extracellular domain of the TSHR serves as its specific autoantigen (35,36). Therefore, TSHR has become an ideal target for immune-modulating therapies (37). In recent years, several drugs targeting major autoantigens, including monoclonal antibodies, small molecules, and peptides, or those blocking immune pathways, have been tested in clinical trials (38,39). The emergence of immunotherapy-related biologics, small molecules, and peptide immunomodulators acts through multiple mechanisms, such as rituximab (40), iscalimab (41), and belimumab (42,43) that directly target B cells or their associated intercalators and cytokines to block B-cell activation or activity. Additionally, specific modulation of TSH via small-molecule antagonists (40) or antagonistic TSHR monoclonal antibodies (e.g., K1-70) has also been examined (44,45). These therapies have shown a degree of efficacy and safety in clinical trials; however, further studies are necessary to validate their long-term efficacy and safety, as well as to determine the most appropriate indications and treatment regimens.

Certain limitations should be noted. First, the analysis was based solely on the Web of Science Core Collection (WoSCC). Although this database offers standardized and widely used citation data, it may not capture all relevant literature, particularly studies published in specialty journals such as those in cardiology, nuclear medicine, or ophthalmology. These journals, though clinically meaningful, are often underrepresented due to lower citation impact or limited indexing in WoSCC. Second, the search included only English-language publications. While no filters were applied for journal type or subject category, this language restriction may have excluded important contributions from non-English-speaking countries/regions, especially those in low- and middle-income regions. As a result, some regional perspectives and locally relevant findings may have been missed. Third, like most bibliometric studies, this work relies on citation-based metrics—such as publication counts and journal impact factors—which emphasize research visibility rather than quality or clinical relevance. Highly cited articles may not necessarily reflect methodological rigor or influence on clinical practice. Lastly, we did not assess the clinical quality or real-world impact of the included studies. Our findings reflect academic trends and research activity, not direct clinical guidance. Future studies should consider combining multiple databases (e.g., Scopus, PubMed), including non-English sources, and incorporating expert review or guideline-based citation tracking to better capture clinically impactful research.

Conclusions

This bibliometric analysis offers a comprehensive overview of the research on the diagnosis and treatment of hyperthyroidism over the past two decades. The study highlights the significant growth in publication volume, with the United States, China, and Italy emerging as major contributors to the field. Notably, the research landscape is predominantly shaped by intranational collaborations, with limited international partnerships, suggesting opportunities for future global cooperation to enhance study quality.

The analysis identified key themes in the literature, with a particular focus on Graves’ disease and emerging therapeutic strategies, including immunotherapy. The prevalence of “guidelines” and “diagnosis” as keywords underscores the ongoing importance of standardizing diagnostic and therapeutic approaches. Guidelines from the ATA and ETA have been pivotal in shaping clinical management, with recent updates addressing novel treatment options for conditions such as GO. Immunotherapies targeting autoantigens and immune pathways show promise but require further validation through clinical trials.

This study underscores the evolving nature of hyperthyroidism research, with a discernible shift toward an exploration of innovative treatments, such as biologics and small molecules, within the context of autoimmune disorders such as Graves’ disease. It also highlights the need for more epidemiological studies, particularly in iodine-deficient regions, and emphasizes the importance of expanding international collaboration to improve the global understanding and management of hyperthyroidism.

The findings of this study are instrumental in guiding future research directions, clinical practices, and policy development in the diagnosis and treatment of hyperthyroidism. By offering insights into research trends and pinpointing emerging areas of focus, this bibliometric study serves as a valuable resource for researchers, healthcare professionals, and policymakers in the fields of endocrinology and thyroid disorders.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-228/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-228/prf

Funding: This study was supported by the National High Level Hospital Clinical Research Funding (No. 2023-NHLHCRF-YYPPLC-ZR-09).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-228/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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