Global scientific trends on thyroid disease in early 21st century: a bibliometric and visualized analysis

A total of 69,283 relevant publications were retrieved, of which 66803 were in English, accounting for 96.42%. The trend figure of annual publication volume from 2000 to 2021 is depicted in Figure 2 (2022 is not full-year data and not shown in the figure). Linear regression analysis found that the increase in publications per year was statistically significant (P<0.001) (8). The annual publication volume of Thyroid Disease research tends to rise between 2000 and 2021. In particular, there were 1819 publications on thyroid disease research in 2000. In 2021, the number of publications reached the peak of the annual number of publications, which is 2.75 times the number of publications in 2000.

Globally, 175 countries and regions are already involved in thyroid disease research. The threshold for the number of articles issued by countries/regions was set to 100 and 54 high-yield countries/regions in the Thyroid Release research were obtained. The distribution of high-yield countries/regions is described in Figure 3. The top ten countries ranked by publication volume are shown in Table 1. The United States (16120 counts, 678255 citations) ranks first for both publication volume and citations. This is followed by China (10,565 counts, 141,486 citations) and Italy (6,333 counts, 222,807 citations). Among the top 10 countries, France has the highest average citations (45 avg. Citations). Moreover, China has the highest average publication year, followed by South Korea.

Based on the retrieval results, a total of 4203 journals with publications about thyroid disease research was found. The threshold for journal publication volume was set at 100 articles, and 113 high-yield journals were obtained. These high-yield journals have published 31348 articles, comprising 45.25% of the total publication volume.

Furthermore, a citation analysis on 113 high-yield journals was conducted and an overlay visualization map was constructed (Figure 4). The size of the circle represents the number of publications, and the color range from blue to red denotes the average number of citations from low to high. It can be seen that Thyroid (n=3201) is the most prolific journal in this field, followed by the Journal of Clinical Endocrinology & Metabolism (n=2285) and Clinical Endocrinology (n=1110). The Journal of Clinical Endocrinology and Metabolism (n=140399) is the most cited journal overall, followed by Thyroid (n=113871) and Clinical Endocrinology (n=35716). 14 journals (as shown in red) have an average of more than 40 citations.

32935 institutions were involved in the publication of thyroid disease papers, and the top 20 institutions by publication volume are shown in Table 2. Harvard University (n=1011) is the institution with the highest number of publications, followed by University of Pisa (n=913) and Shanghai Jiao Tong University (n=778). Harvard University(n=59429) is the most frequently cited institution, followed by Memorial Sloan Kettering Cancer Center(n=53014) and University of Pisa(n=44829). Among the top 20 institutions, the Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center have the highest average citations. Besides, Fudan University has the latest average publication year, followed by Shanghai Jiao Tong University and China Medical University. The threshold for institutional publications was set at 100 and 273 high-yield institutions out of 32,935 were identified. Vosviewer was used to conduct co-authorship analysis of 273 high-yield institutions, all of which were in a co-authorship network, consisting of 8 clusters (Figure 5). The red cluster is the largest and consists of 75 institutions. Harvard University has partnerships with 222 high-yield institutions, followed by Johns Hopkins University, with 186 high-yield institutions. Mayo Clinic and The University of Texas MD Anderson Cancer Center both have partnerships with 173 high-yield institutions.

A total of 248011 authors participated in the publication of Thyroid Disease, and the top 20 authors ranked by publication volume are in Table 3. Miyauchi, Akira (n=422) is the author with the highest number of publications, followed by Tuttle, R. Michael (n=236) and Ito, Yasuhiro (n=234). Schlumberger, Martin (n=24839) is the most frequently cited author, followed by Tuttle, R. Michael (n=22632) and Elisei, Rossella (n=15474). On average, Schlumberger, Martin (n=117) is the most frequently cited, followed by Tuttle, R. Michael (n=96) and Elisei, Rossella(n=74). Among the top 20 authors, Baek, Jung Hwan has the latest average publication year, followed by Shan, Zhongyan, and Teng, Weiping.

The author publication threshold was set at 40 articles and 397 highly productive authors from 248011 authors were identified. As demonstrated in Figure 6, a co-authorship analysis on 397 high-yield authors was carried out using Vosviewer. 388 of the 397 high-producing authors formed the largest network of co-authors, consisting of 12 clusters. Tuttle, R. Michael has partnerships with 89 high-yield authors. Secondly, Elisei, Rossella has partnerships with 77 high-yield authors, while Fugazzola, Laura has partnerships with 71 high-yield authors.

A total of 852113 references were cited in 69283 publications, of which 852113 references appeared a total of 2282274 times, with an average of 33 references per publication. The threshold of reference citations was set to 300 times and 130 highly cited references from 852113 reference articles were identified. As shown in Figure 7, a co-citation analysis on 130 highly cited references was conducted using Vosviewe.

The top five articles cited are as follows: Haugen br, 2016, thyroid, v26(citation frequency:4549), Ooper ds, 2009, thyroid, v19(citation frequency:3306), Davies l, 2006, jama-j am med assoc, v295(citation frequency:1700), Hollowell jg, 2002, j clin endocr metab, v87(citation frequency:1454),Mazzaferri el, 1994, am j med, v97(citation frequency:1253).

There are 92426 keywords in 69283 articles. The threshold of high-frequency keywords was set to 20, of which 307 keywords were selected. A Co-occurrence analysis was conducted on 307 high-frequency keywords and a co-occurrence network map was constructed. At the same time, we also built heat maps for a clearer and more intuitive presentation of the results (Figure 8). The co-occurrence analysis of 307 high-frequency keywords formed 6 clusters, represented by different colors (Figure 9). The red cluster consists of 102 keywords and is the largest cluster. Cluster1(red), Cluster2(green), Cluster3(blue), Cluster4(yellow), Cluster5(purple), and Cluster6(light blue)focus on the subject respectively: 1) Thyroid dysfunction and diseases; 2) mechanism of occurrence and development of thyroid cancer; 3) autoimmune thyroiditis; 4) scope and postoperative management of thyroid surgery; 5) fine needle aspiration of thyroid nodules; and 6) radioactive iodine therapy for thyroid cancer.

An Overlay map of 307 high-frequency keywords was constructed (Figure 10). The color of each node in the graph indicates the average year of publication for that node and the year of publication changes from blue to red.

The data shows that from 2000 to 2021, the overall annual number of publications in thyroid disease research has increased each year for the past 21 years, although the number of publications fluctuated slightly in some years. The United States ranks first in both publication volume and citation frequency, and is the leader in this field. Interestingly, in recent years, there has been a rapid increase in research on thyroid disorders in China and Korea, which may be related to the increased incidence and increased interest of researchers (9, 10). In the top 20 institutions concerning publication volume, Harvard University is the most published and most cited institution, collaborating with 222 high-yield institutions and serving as a global hub for research institutional collaboration. Of the 397 high-yield authors, 97% appeared in the collaborative network, suggesting a high level of collaboration among high-yield authors. Among them, Tuttle, R. Michael, Elisei, Rossella, and Fugazzola, Laura, et al. have particularly close collaborations, forming a close cooperative relationship.

In recent years, there has been an increasing interest in Active Surveillance (AS), mainly due to the excellent postoperative performance of patients with papillary thyroid microcarcinoma (PTMC). AS was initially a prospective study that first suggested that patients with PTMC had a relatively low probability of clinical progression. For patients without high-risk features, regular observation is an option, and it is not too late to undergo surgery when the tumor evolve (81). Subsequently, researchers from multiple developed countries conducted experiments, indicating that this method was only effective for low-risk PTMC and that surgery remains the preferred treatment option for high-risk patients (82–84). In addition, recent studies have demonstrated that AS has a lower incidence of adverse reactions and recurrence rate compared to conversion and immediate surgery, and AS can be the first-line treatment of choice for PTMC (85). As a management strategy, it has been endorsed by several organizations, including the Japan Association of Endocrine Surgery and the American Thyroid Association (86–89). Nevertheless, there are also many problems in the management of AS, such as long follow-up times, the limited number of surgeries, and difficulties in specimen collection. Follow-up strategies and timing of interventions for AS require more evidence to confirm its long-term safety. In general, AS is an effective alternative strategy to surgery for low-risk PTC. Currently, concerns about the effectiveness and safety of AS are diminishing, and various versions of the guidelines recommend the implementation of AS.

Thermal Ablation (TA) is a treatment option for PTMC patients in addition to AS and immediate surgery and can significantly reduce the nodule volume, but takes a long time to achieve nodule volume reduction (90, 91). Surgery, as the standard treatment for PTC patients, is the only method to remove the primary lesion and obtain accurate staging and risk stratification. Several studies comparing the effectiveness and safety of TA and immediate surgery have shown no tumor recurrence or distant metastases with both treatments. However, the probability of complications in TA is significantly lower than that in the surgical group, and TA can reduce the probability of hypothyroidism in patients. Besides, patients will have significantly reduced surgical time, recovery time, and hospitalization time (92). The direct comparison between TA and AS currently lacks feasibility. It has been established that TA can address patient anxiety during follow-up and thus avoid surgical delays. Moreover, after five years of follow-up, patients did not develop tumor recurrence, lymph node metastasis, or distant metastases (93, 94). However, TA is not indicated for all types of thyroid nodules, and occasionally incomplete nodal response and local regeneration may occur. At this point, repeat ablation or surgical treatment may be required, which may make the procedure more difficult (95, 96). Hence, prospective studies with larger samples and longer follow-up times are needed to demonstrate its efficacy. Nevertheless, TA can serve as an alternative for low-risk PTMC patients (97).

Anaplastic thyroid carcinoma and metastatic poorly differentiated thyroid carcinoma are highly invasive malignant tumors. Furthermore, despite the availability of several treatments for iodine-refractory thyroid cancers, the overall survival rate remains unsatisfactory, especially in patients with ATC, with a median survival of only 3-5 months (98). The treatment of such tumors with poor prognosis has always been a focus of researchers’ attention. Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFR1, VEGFR2, and VEGFR3; FGFR1, FGFR2, FGFR3, and FGFR4 (99), and its role in RR-DTC has been proved in many countries (100). However, the therapeutic efficacy of ATC remains controversial (101, 102), and it leads to a decrease in quality of life (103). Recently, the combination of lenvatinib and pembrolizumab has achieved encouraging results in the efficacy of ATC/PDTC patients (104), and a larger sample is still needed to monitor the therapeutic effect of the combination of both.

Investigating the mechanisms of thyroid cancer occurrence and development may facilitate new diagnostic and therapeutic biomarkers. LncRNA has been identified as a biomarker for several cancers (105). It is highly expressed in PTC and promotes the growth and metastasis of tumor cells (106). Several lncRNAs, such as MALAT1, BANCR, and PTCSC3, have been identified to promote the proliferation and metastasis of thyroid cancers (107–109). In addition, lncRNA has also been associated with lymph node metastasis (110), and further studies are needed to elucidate the remaining unknown functions of lncRNA. This biomarker provides new evidence for individualized therapy and molecular diagnosis.