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Abstract
Objectives This study examined the association between anthropometric measurements, lifestyle factors and the prevalence of thyroid nodules among adults in Northeast China.
Design We employed a cross-sectional approach involving a questionnaire survey, which focused on participants’ living habits, and a physical examination that included anthropometry and ultrasound imaging.
Setting The data were procured during multiple trips by medical teams from the first hospital of China Medical University to towns in Northeast China.
Participants Of the 1092 participants, 489 did not have thyroid nodules (mean age: 54.02±11.49 years; 297 females (60.7%)), 99 had single thyroid nodules (mean age: 58.19±10.77 years; 59 females (59.6%)) and 504 had multiple thyroid nodules (mean age: 60.05±10.68 years; 394 females (78.2%)). Inclusion criteria mandated participants be over 20 years old without other medical conditions. We excluded individuals who had undergone surgical resection for thyroid nodules.
Results The prevalence of thyroid nodules was significantly associated with being female (OR 2.569, 95% CI 1.937 to 3.405, p<0.001) and increased age (OR 1.054, 95% CI 1.041 to 1.066, p<0.001). This association was more pronounced in those with multiple thyroid nodules. For males under 60, non-smoking was inversely correlated with the prevalence of multiple thyroid nodules (OR 0.321, 95%CI 0.149 to 0.69, p<0.05). For females under 60, diastolic blood pressure (DBP) was significantly linked with the prevalence of thyroid nodules (OR 0.978, 95% CI 2.614 to 2.705, p<0.05).
Conclusions Besides gender and age, the prevalence of thyroid nodules in Northeast China correlates with smoking habits and DBP.
- Ultrasound
- HEALTH SERVICES ADMINISTRATION & MANAGEMENT
- PUBLIC HEALTH
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information. All data generated or analysed during this study are included in this published article.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Few studies have addressed the risk factors of thyroid nodules in Northeast China; this research contributes to bridging this knowledge gap.
Different genders and age groups were examined separately in this study to mitigate potential confounding influences.
The sample of this study is not large enough.
A cross-sectional study can only show the factors that related to the prevalence of thyroid nodules instead of determining the causal relationship between diseases.
Introduction
Thyroid nodules are defined as discrete lesions within the thyroid glands, differentiated from the adjacent thyroid parenchyma tissues. Radiological imaging techniques predominantly diagnose these nodules.1 Data from population-based surveys indicate that the detected prevalence of thyroid nodules through palpation ranges from 4% to 7%. Using imaging techniques results in a detection rate increase exceeding 10-fold.2 3 Advancements in ultrasound and other diagnostic imaging technologies have led to the detection of thyroid nodules in approximately 65% of the general population and in two-thirds of the adult demographic.4–6
Numerous studies over the years suggest that iodine intake is a factor associated with adult thyroid nodules.7–9 The correlation between urinary iodine levels and the prevalence of thyroid nodules takes on a ‘U’ shape. This pattern indicates that both deficient and excessive iodine intake can elevate the prevalence of thyroid ailments, including thyroid nodules.7–9 In response to a historical mild to moderate iodine deficiency, the Chinese government mandated the use of iodised salt nationwide in 1995. So far, Chinese population has consumed iodised salt for over two decades. Nevertheless, iodine consumption varies by region. Northeast China is recognised as an iodine-deficient area. To standardise participants’ water sources, diet and iodine intake, this study was confined to healthy adults from northeast China with consistent dietary patterns.
Numerous studies have investigated various factors associated with the prevalence of thyroid nodules, including obesity, gender, age, smoking, hypertension and insulin resistance. However, the findings are not always consistent.10–17 For instance, research from Beijing, China identified smoking as an independent risk factor for thyroid nodules.18 In contrast, a study from an iodine-rich area in Istanbul found no association between smoking and either the prevalence or size of thyroid nodules in healthy individuals.19 In South Korea, it was observed that patients with thyroid nodules generally had lower height and weight.20 On the other hand, research in Hangzhou, China linked increased height and weight with a higher prevalence of thyroid nodules in females, indicating a potential correlation with obesity, while no such correlation was observed in children based on height.15 Another study from Sichuan, China posited height as an independent factor influencing the occurrence of thyroid nodules in females.21 Additionally, Argentine research connected insulin resistance with the development of thyroid nodules, and similar findings were echoed in a Turkish study emphasising insulin resistance as an independent risk factor, especially in iodine-deficient settings.12 22 Furthermore, a case–control study in Hefei, China revealed a significant association between diastolic blood pressure (DBP) and the risk of developing thyroid nodules.23
Based on these varied findings, it is hypothesised that regional differences may influence the risk factors associated with the prevalence of thyroid nodules. The objective of this study was to evaluate the prevalence of thyroid nodules in northeast China and to ascertain the relationship between thyroid nodule occurrence and specific physical indicators and lifestyles of the local population.
Thyroid nodules are classified into two types: solitary nodules and multiple nodules.24 25 A solitary thyroid nodule is characterised by a single mass in the thyroid gland, while multiple thyroid nodules represent the occurrence of several masses. Though multiple thyroid nodules are more prevalent, solitary nodules present a greater malignancy risk compared with multiple nodules.24 26 In this study, analysis will be conducted based on the presence or absence of thyroid nodules and their classification (solitary or multiple) to pinpoint the risk factors for thyroid nodules in adults from northeast China.
Methods
Study population and settings
Northeast China is an area deficient in iodine. For the accuracy and reliability of this research, the study focused on 1092 healthy adults from Northeast China, all of whom maintained consistent dietary habits (online supplemental file 1). Data collection spanned from November 2019 to November 2020.
Supplemental material
To qualify for this research, individuals had to be aged above 20 and could not have any medical conditions other than thyroid nodules, such as diabetes, heart disease, cancer or thyroid dysfunction. Furthermore, participants who had previously undergone surgical resection for thyroid nodules were excluded. All participants gave written consent for their involvement. Medical teams from the aforementioned hospital undertook multiple visits to various towns in Northeast China for data collection. The size of the study was contingent on the local population, participation interest and the count of eligible individuals
Lifestyle recording and anthropometric measurements
Data were collected through two primary methods: a questionnaire survey and a physical examination. The questionnaire mainly focused on the participants’ basic lifestyle habits (online supplemental file 2). Physical examinations encompassed anthropometry and ultrasound imaging, both of which pose no harm to individuals. Based on discrepancies observed in various studies regarding potential risk factors for thyroid nodules,10–23 the following parameters were considered in this study: lifestyle choices (smoking: yes/no, drinking: yes/no), and anthropometric data such as gender, age, height, weight, systolic blood pressure (SBP), DBP and heart rate. Height and weight measurements were accurate to 0.1 cm and 0.1 kg, respectively. The body mass index (BMI) was derived using the formula: weight (in kilograms) divided by the square of height (in metres).
Supplemental material
Thyroid nodule diagnosis
All participants underwent an exhaustive thyroid ultrasound examination. This examination was conducted by four seasoned ultrasound radiologists and included a conventional B-scan along with a colour Doppler analysis to assess the blood flow within the thyroid nodules. The diagnostic tool employed was a high-resolution sonograph from Supersonic, France, fitted with a 4–15 MHz linear probe (SL15-4). A nodule was confirmed if its diameter was ≥3 mm. The characteristics of thyroid nodules, such as number, size, location, echo, central and peripheral blood vessels, calcification and shape, were meticulously recorded. Whenever ‘nodule size’ is referenced, it pertains to its maximum diameter.
Statistical analysis
To eliminate the bias caused by gender or age, risk factors were assessed separately based on gender and age groups. Gender was divided into female and male, and further divided into less than 60 years old and more than or equal to 60 years old according to age. Further risk factor correlation analysis was carried out in each subgroup. For normally distributed data, the t-test was used for comparisons between two groups, while one-way analysis of variance was employed for comparisons across multiple groups. These data were denoted as (
±S). In cases where the data did not follow a normal distribution, comparisons between two groups were made using the Mann-Whitney U test, and the Kruskal-Wallis test was applied for comparisons among multiple groups. Such data were expressed in quartiles, represented as (P50 (P25, P75)). For non-ordinal count data, the χ2 test was applied, and for ordinal count data, the rank sum test was employed. Logistic regression facilitated the analysis of factors influencing the occurrence of thyroid nodules.
Statistical significance was set at a two-tailed p<0.05. All statistical evaluations were carried out using the SPSS software, V.25.0 (SPSS).
Patient and public involvement
No patients participated in the design, recruitment or execution of the study. After the evaluations, the findings from the anthropometric measurements and ultrasonography were promptly shared with the patients.
Results
The study encompassed a cohort of 2838 participants from Northeast China. Following the exclusion of individuals aged over 20, those with severe illnesses, and those who had undergone thyroid surgery, 1372 participants fulfilled the criteria. Subsequently, participants with incomplete data were further excluded, resulting in the final inclusion of 1092 participants for the statistical analysis. The flow chart is shown in online supplemental file 1.
To ensure the minimisation of potential confounding variables and bolster the dependability of the outcomes, participants were classified in accordance with the established population categorisation of the WHO ((https://www.who.int/health-topics/ageing%23tab=tab_1)). This classification encompassed the separation of participants into discrete male and female categories, alongside stratification into two age groups: individuals aged 60 years or older and those below 60 years.
Female gender and older age are risk factors associated with the prevalence of thyroid nodules
Of the 1092 participants, ultrasound examinations revealed that 489 had no thyroid nodules (mean age: 54.02±11.49 years; 297 females (60.7%)), while 603 had thyroid nodules. Among those with nodules, 99 participants had solitary thyroid nodules (mean age: 58.19±10.77 years; 59 females (59.6%)), and 504 had multiple thyroid nodules (mean age: 60.05±10.68 years; 394 females (78.2%)). Compared with individuals without nodules, patients with thyroid nodules were significantly correlated with female gender (OR 2.569, 95% CI 1.937 to 3.405, p<0.001) and increased age (OR 1.054, 95% CI 1.041 to 1.066, p<0.001). This association was more pronounced among individuals with multiple thyroid nodules (gender OR 3.187, 95% CI 2.346 to 4.329, p<0.001; age OR 1.06, 95% CI 1.046 to 1.073, p<0.001) than those with a solitary nodule (gender OR 1.064, 95% CI 0.671 to 1.678, p>0.05; age OR 1.032, 95% CI 1.011 to 1.053, p<0.05). The detailed results are presented in tables 1–2.
Single factor analysis of age and gender in subjects
Logistic regression analysis was used for further analysis of age and gender in subjects
To enhance the credibility of other variables, participants were grouped by gender and age. Both female and male participants were divided into people aged ≥60 and <60 according to WHO criteria for population classification (https://www.who.int/zh).
Predictors of thyroid nodule presence in distinct groups
The results detailed below are presented in tables 3–5. There was no significant correlation between the prevalence of thyroid nodules and variables such as heart rate, drinking habits, BMI, SBP and weight across all groups. However, the influence of smoking, age, DBP and height on the prevalence of thyroid nodules varied across groups.
Single-factor analysis of variables in subjects with or without thyroid nodules
Single-factor analysis of variables among three groups
Logistic regression analysis was used for further analysis of variables with significant differences in single factor analysis of variables among subjects
In males under 60 years, 103 did not have thyroid nodules, presenting with a median age of 50, mean BMI of 25.53, mean SBP of 141, mean DBP of 91.7, mean heart rate of 66, mean height of 170.2 cm, and mean weight of 74.3 kg; 63.33% consumed alcohol, and 57.35% smoked. Among the 55 males with thyroid nodules, 17 had solitary nodules, characterised by a median age of 46, mean BMI of 26.06, mean SBP of 130, mean DBP of 90.35, mean heart rate of 66, mean height of 171.82 cm, and mean weight of 77 kg; here, 8.33% consumed alcohol, and 10.29% smoked. The remaining 38 had multiple thyroid nodules, with a median age of 53, mean BMI of 26.84, mean SBP of 141, mean DBP of 92.32, mean heart rate of 71.5, mean height of 170.68 cm, and mean weight of 78.81 kg; 28.33% were drinkers, and 32.35% smoked. Analysis revealed a significant correlation between smoking and the presence of thyroid nodules, particularly multiple nodules (OR 0.321, 95% CI 0.149 to 0.69, p<0.05).
Among males over 60 years old, 89 exhibited no thyroid nodules, with a median age of 66, mean BMI of 24.16, mean SBP of 145, mean DBP of 90.43, mean heart rate of 69, mean height of 166.66 cm, mean weight of 67.66 kg, 50% identified as drinkers and 50.72% as smokers. Ninety-five presented with thyroid nodules. Out of these, 23 had a single thyroid nodule, and 72 had multiple thyroid nodules. For those with single thyroid nodules: median age was 67, mean BMI was 25.08, and 17.31% were drinkers while 10.14% were smokers. For those with multiple thyroid nodules: median age was 69, mean BMI was 23.9 and 32.69% were drinkers while 39.13% were smokers. Statistical analysis indicated a significant correlation between age and the prevalence of thyroid nodules (OR 1.096, 95% CI 2.804 to 3.209, p<0.05). This correlation was particularly pronounced for multiple thyroid nodules (OR 1.112, 95% CI 1.049 to 1.178, p<0.001). However, there was no significant correlation between smoking and the occurrence of thyroid nodules in this age category.
In females under 60 years, 217 displayed no thyroid nodules. Their median age stood at 48 years, with a mean BMI of 24.9, mean SBP at 137, mean DBP at 88, mean heart rate at 70, mean height at 159 cm and mean weight at 63.4 kg. Among them, 45.45% consumed alcohol, and 41.67% smoked. Of the 218 females who exhibited thyroid nodules, 33 had solitary nodules, characterised by a median age of 53 years, mean BMI of 25.36, mean SBP of 135, mean DBP of 88, mean heart rate of 70, mean height of 156 cm and mean weight of 63.3 kg. Only 4.55% consumed alcohol, and 16.67% were smokers. The remaining 185 had multiple thyroid nodules. Their median age was 52 years, with a mean BMI of 24.72, mean SBP of 139, mean DBP of 86, mean heart rate of 70, mean height of 159 cm, and mean weight of 62.3 kg. In this subgroup, 50% consumed alcohol and 42.11% smoked. An analysis contrasting those with and without thyroid nodules revealed a significant association between age and DBP concerning nodule prevalence (age OR 1.061, 95% CI 2.812 to 2.971, p<0.001; DBP OR 0.978, 95% CI 2.614 to 2.705, p<0.05). A direct correlation emerged: as age increased or DBP decreased, the prevalence of thyroid nodules rose. However, when discerning factors influencing single versus multiple nodules, age and DBP lacked significance. Only height exhibited a statistical difference in univariate analysis (p=0.042), but this distinction disappeared in logistic regression.
In females aged over 60, among the 80 without thyroid nodules, the median age was 65, with a mean BMI of 25.15, mean SBP of 158, mean DBP of 91.5, mean heart rate of 70.5, mean height of 155.38 cm, and mean weight of 61.14 kg. 25% consumed alcohol and 15.38% smoked. On the other hand, 235 had thyroid nodules. Of this group, 26 had a solitary nodule, with a median age of 67, mean BMI of 24.7, mean SBP of 149, mean DBP of 89.5, mean heart rate of 71.5, mean height of 153.44 cm and mean weight of 59.11 kg. None reported alcohol consumption or smoking. The remaining 209 females exhibited multiple thyroid nodules. Their median age was 66, with a mean BMI of 24.84, mean SBP of 153, mean DBP of 89, mean heart rate of 71, mean height of 155.72 cm and mean weight of 61.15 kg. In this subset, 75% consumed alcohol and 84.62% smoked. On analysis, age was significantly associated with thyroid nodule prevalence (OR 1.062, 95% CI 2.721 to 3.083, p<0.05). However, the presence of single vs multiple nodules showed no significant difference.
Discussion
Based on the aforementioned results, and in line with our hypothesis, the risk factors associated with the prevalence of thyroid nodules vary across regions, age groups and genders. Over half of the participants in this study were diagnosed with at least one thyroid nodule. Females exhibited a higher susceptibility to thyroid nodules compared with males, and age showed a positive correlation with the prevalence of these nodules.11 27–31 Notably, prior research has indicated that the elderly, in addition to having a higher prevalence of thyroid nodules, also present with an elevated rate of malignancy.28 29 32–34
A majority of the risk factors for the prevalence and malignant transformation of thyroid nodules cannot be controlled, including age, gender and family history. Fortunately, our study has identified several modifiable factors. For males under 60, smoking was not only a significant risk factor for the presence of thyroid nodules but also increased the likelihood of multiple nodules. Smoking has been shown to inhibit iodine transport and elevate iodide efflux, potentially contributing to the development of thyroid nodules.35 36 Additionally, smoking can lead to elevated serum calcitonin levels, influencing the onset, treatment and prognosis of medullary thyroid carcinoma.37 For females under 60, a lower DBP emerged as a risk factor linked to the prevalence of thyroid nodules. Metformin treatment has been found to considerably decrease thyroid stimulating hormone (TSH) levels and the size of thyroid nodules, although it significantly raises DBP without notably affecting SBP or BMI.14 38 39 While a study from Italy suggested a correlation between BMI and thyroid nodule prevalence, however, our study along with a cross-sectional study of 121 702 participants from southwestern China, found no such association.27 31 Thus, to enhance thyroid health and avoid unnecessary medical interventions for thyroid nodules, individuals can modify certain lifestyle habits, like quitting smoking and managing blood pressure, to mitigate the risk of developing thyroid nodules.
The adjustment of living habits mentioned above will also contribute to the recovery after thyroid surgery. The common treatments for thyroid nodules include radiofrequency ablation and partial or total resection of the thyroid.40 Common postoperative complications include bleeding, hypothyroidism, voice changes, hypocalcaemia and scarring.40 41 Among them, bleeding after thyroid and/or parathyroid surgery is a life-threatening emergency.42 On univariate analysis older age, higher BMI and higher postoperative blood pressure were identified as risk factors for postoperative bleeding.41 43
This study has several inherent limitations. First, the sample size not be adequately large. Second, the potential risk factors for the prevalence of thyroid nodules are not comprehensive enough. Third, accurate measurements of iodine intake were not conducted through urine or blood tests. Finally, while cross-sectional studies can identify factors associated with the prevalence of thyroid nodules, they cannot establish causal relationships between these factors and the nodules.
Conclusion
In a study comprising 1092 permanent residents of Northeast China, the sample included 492 males (158 under 60 years old and 334 over 60 years old) and 600 females (435 under 60 years old and 165 over 60 years old). Out of the participants, 489 did not present with thyroid nodules, while 603 did. Among the latter group, 99 had a solitary nodule, and 504 exhibited multiple nodules. From the analysis, it was observed that the prevalence of thyroid nodules in Northeast China is associated with factors such as gender, age, smoking habits and DBP. Particularly, females and older individuals have a higher incidence of multiple thyroid nodules. For males under 60, smoking emerged as a significant risk factor for thyroid nodules. A lower DBP correlated with an increased prevalence of thyroid nodules in females under 60.
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information. All data generated or analysed during this study are included in this published article.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and was approved by Medical Research Ethics Committee of the First hospital of China medical UniversityID:2019-187-3. Participants gave informed consent to participate in the study before taking part.
Acknowledgments
We extend our gratitude to all the patients who participated in this study. Additionally, we are indebted to Professor Hailong Wang from the Department of Epidemiology and Evidence-based Medicine at the First Hospital of China Medical University for his invaluable guidance on the statistical methodologies employed in this research.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors ZZ acted as guarantor for this study. All authors, with the exception of YY, JS and ZZ, were involved in data collection. YY took the lead in data analysis and authored the initial draft of the manuscript. The study’s conception and design were orchestrated by WT, KH, GY, SL and JD. All authors provided critical feedback and contributed to the manuscript’s development. The decision to submit and publish the manuscript was unanimous among all authors.
Funding This research was supported by the Natural Science Foundation of Liaoning Province, China (2019-ZD-0772), the National Natural Science Foundation of China (No. 81971639) and the Major special project of the Ministry of Science and Technology of the People's Republic of China (2018yfc2000301).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.