Papillary thyroid carcinoma (PTC), a common type of endocrine tumor, comprising approximately 90% of thyroid malignancies, has been increasing for several decades (1). To a large extent, genetic and environmental elements, as well as factors about lifestyle, are mainly responsible for this phenomenon of tumor growth. As we all known, obesity is a common public health problem all over the world and the percentage of obese adults has increased stably over the past two decades in China. Epidemiological evidence has demonstrated that higher body mass index (BMI) is slightly but significantly linked with the incidence of thyroid cancer. Moreover, these data identified that obesity may be a driving factor for the development of PTC (2, 3). Despite the existence of studies demonstrating the impact of obesity on thyroid cancer, other studies failed to confirm this association between increased BMI and aggressive features of PTC (4, 5).

Since radioactive iodide (RAI) therapy is an important adjuvant remedy for the management of PTC disease, a more important issue is represented by the question of whether or not to consider increased BMI as a risk factor of poor clinical response of high-dose RAI therapy (6). Conflicting reports have also been released on the clinical outcome in obese patients with thyroid cancer. Most studies have shown no differences in clinical outcomes of thyroid cancer after RAI therapy between obese and normal weight patients (7, 8). Very recently, Mele et al. reported that their results reflected a potential role for BMI as a predictor of early DTC relapse (9). Compared with those in Western countries, the Chinese population has a diverse lifestyle and dietary habit.

Based on these considerations, we were intrigued to analyze the clinical manifestations, pathological features, and the response to RAI therapy of a group of consecutive Chinese PTC patients in order to evaluate the relationship between BMI at the time of the therapy, aggressiveness of PTC, and clinical response during the follow up.

Although there is no definite link between thyroid cancer and increased BMI, the suggestion that obesity is the cause of many chronic diseases and special types of cancer is widely accepted. A series of studies have researched the role of obesity in the aggressiveness of the course of thyroid cancer (10, 11). However, these results are mixed. In a cohort of 2,057 thyroid cancer patients, for example, Kim et al. demonstrated that a higher level of BMI was associated with advanced TNM stage (12). However, Matrone et al. found no connection between aggressiveness and BMI in thyroid cancer patients (13). These conflicting data may partially be explained by differences in population characteristics, sample capacity, and BMI threshold setting. We investigated the influence of BMI as a continuous variable on aggressive features and clinical responses in PTC.

We evaluated the clinical features of 337 consecutive PTC patients after high-dose radioactive iodine therapy. We did not find any significant differences regarding histology, Hashimoto thyroiditis, and N stage among the four groups of patients. However, our results are in line with those of Kim et al., in which the researchers did find that higher BMI was significantly associated with larger tumor size, multifocality, and more advanced T stage. By contrast, Kwon et al. showed that higher BMI was not related with clinical features of thyroid cancer (11). In their study, the median BMI value was 28.1 kg/m². In our study, the median BMI value was lower (24.2 kg/m²). Typically, Asians are less obese, and their habitual diet is different to that of Caucasians. In the Kim et al. study, the median BMI was 23.8 kg/m² and all patients were Korean. The population constitution of our research resembled the range of obesity and race in the Kim et al. study, which may be responsible for the similarity of results. Findings identical to those of Kim et al. were also obtained in studies performed in China (14, 15). However, Chiara Mele et al. highlighted a potential association between metabolic setting, circulating adipokines, and thyroid cancer phenotype. And it was confirmed that obesity was associated with lymph node metastases in patients with DTC (9).

A lack of connection between BMI and DTC aggressive features was also documented by Polish et al. in a large cohort of 1,181 patients (16). In that study, approximately 30% of patients did not undergo radioactive iodine therapy and about 70% of the patients were low risk. Unlike with the Polish study, all of our patients underwent total thyroidectomy, followed by radioactive iodine treatment. Furthermore, compared to the Polish study, our study group revealed aggressive features due to a greater number of intermediate and high recrudescence risk patients (58.8% vs 26.4%; 29.1% vs 18.7%).

Besides, our research has no evidence to confirm that thyroid cancer with diabetes promotes the invasive growth of tumors. However, Li et al. has shown that PTC complicated with diabetes has a higher risk of invasive tumor growth (17). In our study, the ratio of thyroid cancer with diabetes was low, which may affect the role of diabetes in tumor invasiveness and clinical outcome.

In addition, higher TSH levels have been considered as factors that boost the invasiveness of PTC (18). The positive association between TSH level and BMI has also been reported in previous studies, including a recent one that analyzed a cohort of 432 prospectively followed patients. But the serum TSH levels were similar in all four BMI groups.

As far as radioactive iodine therapy was concerned, we did observe significant differences among the four groups, in terms of 131I uptake and of the Tg level before 131I treatment. When using the definition of first reaching ER as the endpoint event, we found that no differences in the clinical outcome were noted depending on BMI. Our results agree with those of Chung et al., in which the authors did not find a significant difference between BMI groups in the outcome of the disease (19).

This work also has some limitations. Firstly, because this was a prospective study, the sample size we included may not have been large enough. Thus, this study defined obesity based solely on BMI, similar to many other studies. Thirdly, our follow-up time was shorter than other studies.

In conclusion, in our cohort of Chinese subjects we demonstrated that BMI may have an additive effect on the aggressiveness of PTC, but may not have an effect on the response to therapy after high-dose radioactive iodine therapy.

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

The studies involving human participants were reviewed and approved by the institutional ethics committee of the Second Hospital of Shandong University. The patients/participants provided their written informed consent to participate in this study.

Conception and design: WZ. Collection and assembly of data: XZ and XL. Data analysis and interpretation: YS and CY. Manuscript writing: JC. Final approval of the manuscript: All authors.

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

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