Thyroid cancer is the most common endocrine malignant tumor. According to the histopathological type, it can be divided into medullary thyroid carcinoma (MTC), anaplastic thyroid carcinoma and differentiated thyroid cancer(DTC), which includes papillary thyroid cancer, follicular thyroid cancer (1). MTC is a special type of thyroid cancer derived from the C cell of the thyroid gland, with elevated plasma calcitonin and carcinoembryonic antigen, accounting for about 2% of all thyroid carcinomas (2). Depending on the clinical symptoms of MTC, it can be classified as hereditary (75%) and sporadic (25%) (3). Compared with DTC, MTC is more likely to find local lymph nodes metastasis, and the overall 10-year survival rate of MTC ranges 61-76% (4). Total thyroidectomy and dissection with or without cervical lymph node compartments is standard treatment for patients with MTC (5). Recently, as a poorly prognosed thyroid carcinoma, a large number of studies have been conducted on MTC.

Bibliometric analysis is an effective tool. By summarizing and analyzing the data of countries and regions, journals, authors, keywords, citations, bibliometric analysis can visually reveal the developing process, current status and hotspots of researches in one field as well as predict the global trends in the future (6, 7).

Recently, the application of bibliometric analysis in the field of thyroid research is focused on diseases such as papillary thyroid cancer (8) and anaplastic thyroid cancer (9). To our acknowledge, there is no bibliometric analysis on MTC. Then, we searched “medullary thyroid carcinoma OR thyroid AND carcinoma, medullary” and “Bibliometrics OR Bibliometric” on Web of Science and PubMed, and no relevant papers were found. As the first bibliometric analysis on MTC, this study aims to use bibliometric methods to reveal the development process, current status, hotspots and predict global future trends in the field of MTC research.

MTC is a rare type of thyroid cancer with a poor prognosis. In recent years, researchers have conducted numerous studies on the pathogenesis and treatment of MTC in order to improve the prognosis of MTC patients, while no bibliometric article on MTC has been published worldwide. This paper is the first bibliometric analysis on the field of MTC research, visualizing 1208 publications in the field of MTC from 2012 to 2021 in terms of trends in publication, most scientifically productive countries, organizations, journals, authors, keywords and citations. This research reveals the development process, current research status and hotspots in the field of MTC from 2012 to 2021, and predicts global trends in this field.

From 2012 to 2021, the average annual number of articles in the MTC field was stable above 105, which reached a peak of 140 articles per year in 2020 and 2021 ( Figure 2 ), indicating that MTC had been a hot pot and received increasing attention in recent years.

The top ten most productive countries were concentrated in the Americas, Asia and Europe, which proved that the publication situation in this research area was not evenly distributed at the world level. And the United States and Italy were leading in publication energy and citations, further revealing the dominance of the United States and Italy in the field of MTC research and the high quality of publications ( Table 1 ). The partnership mapping of the top ten countries of publication showed that the United States, Italy, and China, which had the highest number of publications, had more cooperation with other countries, suggesting frequent cooperation among the most productive countries in MTC research and a good international exchange pattern ( Figure 3 ).

An analysis of the organization of the literature is key to identifying the core organizations in the field. The top three publishers among the 1,734 institutions covered in this article were University of Texas MD Anderson Cancer Center, University of Pisa, and University of Padua, all from the United States or Italy. In addition, the top ten organizations publishing papers were from the United States and Italy, accounting for six of them. This result was consistent with the results of the national bibliometric analysis, proving once again that the United States and Italy were located at the center of this research field ( Table 2 ).

Analysis of the authors of the papers reveals the representative scholars and core research strengths in the field of research. The top author in the field of MTC in the last 10 years was Luca Giovanella, with 24 publications, mainly devoted to the study of MTC diagnosis (15), including the evaluation of the diagnostic efficacy of fine needle aspiration cytology (16) and calcitonin levels in fine needle aspiration cytology (17), ultrasound (2, 18) and positron emission tomography/computed tomography (19). The second most published and most cited author, Rossella Elisei, whose main research interests were targeted therapies (20) and RET mutations (21). He was engaged in the revision of the 2015 edition of the MTC management guideline, which was responsible for its most cited authorship. His engagement in the revision of the 2015 edition of the MTC management guideline was what made him the most cited author. With the most average citations, Henning Dralle and Andreas Machens came from the same institution, and were also engaged in the revision of the 2015 edition of the MTC management guideline, their main research interests were the prognosis of MTC surgery at different stages (22, 23). All of these authors were leading scholars in the field of MTC research and had played an important role in the development of the field.

According to Bradford’s law, we calculated the number of core journals in the field of MTC from 2012 to 2021 to be about 8 ( Table 4 ), and the 3 most published journals were Thyroid, Endocrine, and Diagnostic cytopathology, with the most cited journal being Journal of clinical endocrinology & metabolism. These journals were mostly in the field of thyroid and internal division diseases and their pathology, all of which were of great importance and influence in the field of thyroid.

The keyword co-occurrence map reflects the distribution of research directions in a given field over time. Figure 4 revealed that the main research directions in the field of MTC research in the last 10 years had been diagnostic, non-surgical treatment, surgical treatment, genetic and related to other endocrine diseases. The table of the top 20 most important keywords ( Table 5 ) indicated that prognosis of MTC, RET gene mutations, therapeutic measures, plasma calcitonin, and interventions had been the main research features in the field of MTC in the last 10 years. Burst keywords represent the cutting-edge topics in a certain field at a certain time. The 12 burst words in Figure 5 indicated that between 2012 and 2021, the research frontier in this field had gone through a total of three phases. The first phase was dominated by targeted therapies and clinical trials, the second phase, by molecular research, and the third phase, by outcome. Meanwhile outcome is also a recent research frontier in the field of MTC and a global trend in the coming years.

Analyzing highly cited literature helps to have a clearer understanding of the current development of a field. As shown in Table 6 , articles with article type review, content MTC guidelines, and targeted therapies were prone to be highly cited articles in this field. The 2015 edition of the revised MTC management guideline (5) states that FNAC, ultrasound, plasma calcitonin concentration, carcinoembryonic antigen values, and RET gene mutation status can be used as assists in the diagnosis of MTC. For patients without distant metastases, total thyroidectomy and dissection with or without cervical lymph nodes metastasis is the primary recommended therapy. For patients with MTC with distant metastases, treatment of the original site or systemic therapy, such as systemic therapy with tyrosine kinase inhibitors and clinical trial, can be considered. tyrosine kinase inhibitors is the most commonly used targeted therapy with MTC. In recent years, vandetanib and cabozantinib have been used to treat advanced MTC, and studies of their efficacy are gradually being conducted (24–26). At the same time, the efficacy of other tyrosine kinase inhibitors drugs such as sunitinib in MTC is also being investigated (27, 28).

Co-citation analysis can characterize the internal structure of knowledge based on co-cited references. Figure 6 showed the top 50 cited journals among 1208 articles. These journals could be roughly divided into 4 major categories, covering endocrine-related and surgical direction, MTC pathology direction, MTC oncology, molecular. Citing these articles provided a basis for clinical interventions, facilitates a more in-depth understanding of the pathological features of MTC, and provided a basis or ideas for the exploration of tumor mechanisms.

This study also has some limitations. Firstly, these articles are from the Web of Science core collection of Science Citation Index Expanded and Social Sciences Citation Index. Secondly, the language of the publications is set to English and the type of the publication is set to article or review. These mentioned above may make some relevant publications missing. However, it is generally accepted that these articles represent a very small fraction of all articles and have little impact on the result of our findings (29). The inclusion of case reports and cases series in the bibliometric analysis could be considered in future studies, which may provide more precise hints on the direction of research at the frontiers of MTC, such as rare gene fusions and TKI therapeutic breakthroughs.

In general, the research of MTC is currently in a booming phase. Gene mutation, targeted therapy, mechanism and prognosis of MTC are all hot directions, and, outcome is the frontier hot spot. In the future, more related research is expected to be conducted, and research based on the above directions will become the mainstream of MTC research, which is important for the diagnosis and treatment of MTC and improving the prognosis of patients.

In summary, researchers had conducted numerous studies on MTC from 2012 to 2021.The United States and Italy and their institutions were leaders in MTC research, with the highest scientific productivity. Luca Giovanella was the most published author. Thyroid, Endocrine, Diagnostic cytopathology, Journal of clinical endocrinology & metabolism were the most important core journals in the field. Outcome, RET gene mutations, interventions, plasma calcitonin, and targeted therapy were hot research topics in the field of MTC. Outcome was a cutting-edge topic and global trend in the field of MTC research.

Overall, this study is the first bibliometric analysis of MTC research. This study analyses the publications in the field of MTC and presents them in a visual way, revealing to a certain extent the development process, research hotspots and future global trends, which may provide ideas for further research.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

This work was conceived by RL. Data was collected and downloaded by RL, WY and ZZ. The visualization work was performed by RL. The manuscript was written by RL. XL, ZL, WY and ZZ helped to revise manuscript and proposed constructive opinions. All authors contributed to the article and approved the submitted version.