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BMJ Open logoLink to BMJ Open
. 2017 Oct 30;7(10):e016706. doi: 10.1136/bmjopen-2017-016706

Associations of adiposity measurements with thyroid nodules in Chinese children living in iodine-sufficient areas: an observational study

Na Wang 1, Hong Fang 2, Chaowei Fu 1, Peixin Huang 3, Meifang Su 4, Feng Jiang 1, Qi Zhao 1, Yue Chen 5, Qingwu Jiang 1
PMCID: PMC5665290  PMID: 29084792

Abstract

Objectives

Obesity has been found to be associated with an elevated risk of thyroid nodule(s), mainly in adults; however, evidence for this association in children was limited. The objective of this study was to investigate the association of adiposity and thyroid nodule(s) in children living in iodine-sufficiency areas.

Setting and participants

We conducted a cross-sectional study of 1403 Chinese children living in the East Coast of China in 2014.

Outcome measures

Anthropometric measures including height, weight and waist and hip circumferences were taken, and body mass index (BMI), body surface area (BSA) and waist–hip ratio (WHR) were then calculated. Thyroid ultrasonography was performed to assess thyroid volume and nodules.

Results

Based on BMI, 255 (18.17%) children were overweight and 174 (12.40%) were obese. Thyroid nodule(s) was detected in 18.46% of all participants and showed little age and sex variations. As compared with normal-weight children, obese children experienced significantly higher risks for solitary (OR 2.07 (95% CI 1.16 to 3.71)) and multiple (OR 1.67 (95% CI 1.03 to 2.70)) thyroid nodules. Similar associations with thyroid nodule(s) were observed with adiposity measured by waist circumference and BSA, but not WHR. There were no notable differences in the associations between children consuming iodised and non-iodised salt.

Conclusions

These findings provide further evidence that childhood obesity is associated with the risk for thyroid nodule(s).

Keywords: adiposity, thyroid nodule(s), children, iodine


Strengths and limitations of this study.

  • Large sample size, directly measured thyroid ultrasonography and various anthropometric measurements following a standardised protocol.

  • Detailed information distinguishing solitary and multiple nodules and household iodised salt consumption status at the individual level.

  • Lack of information on thyroid function.

Introduction

Thyroid nodule (TN) is a common thyroid disorder globally, and the incidence has been increasing in recent decades.1 2 Thyroid ultrasound investigations have documented very high prevalences (approaching 50%) of TNs worldwide.3–5 Potential risk factors for TNs include age, sex, iodine intake,3 6–8 demographic parameters, clinical history and waist circumference (WC).2 9 Both mildly deficient iodine intake and excessive iodine intake are risk factors for TN(s) in normal subjects.10

Obesity is a known risk factor for a number of chronic conditions and may also increase the risk of thyroid cancer.11–15 The recent increase in TNs and thyroid cancer may partly be due to the epidemic of obesity.9 16 17 Elevated thyroid-stimulating hormone levels and declined free thyroxin (FT4) levels have been observed in obese patients.16 However, previous studies of the associations between obesity and thyroid were mainly conducted in adults, and the results were not entirely consistent. Whether these observations from adults can be applied to children is not clear particularly because the incidence of TNs is lower but the risk for malignancy is greater in children as compared with adults.18

In the current study, we conducted a large-scale epidemiological study to determine the associations of a number of anthropometric measurements including body mass index (BMI), body surface area (BSA), WC and waist–hip ratio (WHR) with solitary or multiple TNs in school-age children.

Methods

Study population

Randomised cluster sampling was used to selected subjects. Similar study methodologies have been reported in an earlier study.19 Briefly, three coastal cities in East China (Minhang District in Shanghai, Haimen City in Jiangsu Province and Taizhou City in Zhejiang Province) were selected by purposive sampling. Previous studies have revealed an iodine-sufficient status20–22 along with distinguished iodised salt consumption proportions among three sites. One primary school (students were mainly local residents) was selected from each city to ensure a good representativeness. Four classes in each grade from grade 3 to grade 5 in these schools were randomly selected in 2014 and all students in 12 selected classes in each school were enrolled into this study (figure 1). Among 1444 eligible children, an ultrasound test for thyroid gland volume was performed on 1429 students and 1403 of them completed routine physical examinations. A total of 1375 students provided first morning urine samples. Based on data from 1403 students who completed physical examinations and thyroid test, we determined the prevalence of TN(s) and the influences of overweight and obesity. Written consent from parents or guardians of all participants were received, and the study was approved by the ethical review board of the School of Public Health of Fudan University.

Figure 1.

Figure 1

Flow chart for the study design. UIC, urinary iodine concentration; US, ultrasound.

Study variables

The outcome variables in this study were having TN(s) (no, yes) and number of TNs (no nodule, solitary nodule, multiple nodules). Adiposity measurements were explanatory variables, including BMI, BSA, WCs and WHR. Sex, age, urinary iodine concentrations (UICs) and iodised salt consumption status were covariates in the multivariate regression models.

Anthropometric measurements

Anthropometric measurements, including standing height (cm), weight (kg) and circumferences of the waist, hip and chest (cm) were taken by trained health professionals according to a standard protocol. The standing height was measured to the nearest 0.1 cm without shoes. Weight was measured to the nearest 0.1 kg using a digital weight scale. BMI was calculated as weight in kilograms divided by the square of height in metres, and all participants were categorised into three groups of under/normal weight, overweight and obesity status according to the BMI growth reference values for Chinese children.23 The cut-offs for overweight and obesity in boys were 17.8 and 20.1 for age 8, 18.5 and 21.1 for age 9, 19.5 and 22.2 for age 10 and 20.1 and 23.2 for age 11. The corresponding cut-offs for girls were 17.3 and 19.5, 17.9 and 20.4, 18.7 and 21.5, and 19.6 and 22.7, respectively. BSA was calculated by using the following formula: BSA=(Weight0.425)×(Height0.725)×0.007184.24 WHR was calculated as WC divided by hip circumference. BSA, WC and WHR were categorised into quintiles to assess their relations with TNs.

Thyroid ultrasonography

All participants received thyroid ultrasonography performed by experienced examiners at school using a real-time sector scanner with a 7.5 MHz/40 mm probe linear transducer. The ultrasonographic examination was carried out on the children lying on a desk with the neck extended. Standardised thyroid ultrasound technique was adopted according to the method described by Fuse et al.25 Discrete lesion(s) within the thyroid gland that was palpably and/or ultrasonographically distinct from the surrounding thyroid parenchyma was defined as TN(s).26 In case of abnormality in the sonographic examination of the thyroid, parents of the children would receive a written note describing the abnormal results of the examination and be advised to take their children to visit a physician. All participants were categorised as having no nodule or having nodule(s) (solitary nodule and multiple nodules) according to their TN detection status.

Urine and salt samples collection and iodine concentration analyses

First, morning urine sample was collected for each participant. Students were also asked to bring a salt sample of more than 20 g from home for iodine measurement.

UIC was determined following the method proposed by the Ministry of Health of the People’s Republic of China (WS/T107.2006 and GB/T13025.7-1999).27 Salt iodine content was also measured using a national standard method with a proper quality control28 (GB/T13025.7-1999). Urine samples (10%) were assayed in duplicate, and no statistical differences were observed as compared with the primary results.

Iodine nutrition status was determined at a population level according to WHO/Unicef/International Council for Control of Iodinedeficiency Disorders (ICCIDD): insufficient (UIC <100 µg/L), sufficient (100–199 µg/L), more than adequate (200–299 µg/L) and excessive (≥300 µg/L). Iodised salt consumption status was grouped into two categories: non-iodised salt (<5 mg/kg) and iodised salt (≥5 mg/kg).29

Statistical analysis

χ2 test was used to examine TNs in relation to sex, age, BMI, iodised salt consumption status, urinary iodine level and study area. Multinomial logistic regression analysis was used to examine the associations of various anthropometric measurements with the frequency of TNs (no nodule, solitary nodule and multiple nodules). Due to a considerable day-to-day variation in iodine excretion, one-spot urinary iodine level was not a proper indicator of iodine status for individuals.30 31 Therefore, in current analysis, iodised salt consumption instead of iodine concentration in urine was included in the multivariate models. We also assessed the correlation between UIC and iodised salt consumption and observed a significantly higher level of UIC in children who consumed iodised salt at home, suggesting that iodised salt consumption status could be a good proxy for iodine nutrition at a population level. Multivariable logistic regression models were then used to adjust for age, sex and iodised salt consumption. Potential effect modifications by sex, age and iodised salt consumption on the associations of interest were also examined by including associated interaction terms into the multivariate analysis. We also reanalysed the data by using mixed effects with survey schools as random effect and observed no statistical significance of random effect in the generalized linear mixed model (GLMM) (p=0.320).

All analyses were performed by using SAS software, V.9.3 (SAS Institute), and all statistical significance was based on two-side probability.

Results

Table 1 shows the demographic characteristics as well as iodine nutrition status for the 1403 participants included in the analysis. The mean age was 9.54 (±0.98) years, the median BMI was 17.05 (IQR 15.55–19.35) kg/m2 and the median UIC was 184.90 µg/L.

Table 1.

General characteristics for children from Shanghai, Haimen and Taizhou, China, in 2014

Male Female
n % n % χ2 p Value
Total 739 52.67 664 47.33
Age (years) 0.788 0.852
 8 116 15.70 111 16.72
 9 246 33.29 215 32.38
 10 237 32.07 204 30.72
 11 140 18.94 134 20.18
BMI 11.56 0.003
 Normal 531 71.85 443 66.72
 Overweight 110 14.88 145 21.84
 Obese 98 13.26 76 11.45
Area 6.182 0.046
 Minhang 294 39.78 226 34.04
 Haimen 234 31.66 214 32.23
 Yuhuan 211 28.55 224 33.73
UIC (μg/L)* 4.198 0.241
 <100 122 17.35 132 20.63
 100–199 282 40.11 226 35.31
 200–299 171 23.14 158 24.69
 ≥300 128 17.32 124 19.38
Iodised salt consumption† 0.015 0.901
 No 250 36.39 235 36.72
 Yes 437 63.61 405 63.28

*A total of 60 missing: 36 (60.00%) were male and 24 (40.00%) were female.

†A total of 76 missing: 52 (68.42%) were male and 24 (31.58%) were female.

BMI, body mass index; UIC, urinary iodine concentration.

TN(s) were detected in 259 children, accounting for 18.46% of all the participants. Most nodules were accompanied by hypoechogenicity. Of the participants, 5.92% (83/1403) had solitary nodule and 12.54% (176/1403) had multiple TNs. The frequency of TNs showed no age-related or sex-related difference (table 2). The median UICs in children without nodules, with single nodule and multiple nodules were 187.80 µg/L, 195.55 µg/L and 160.45 µg/L, respectively (χ2 7.44, p=0.024). The prevalence of multiple TNs was much higher in children consuming non-iodised salt than those consuming iodised salt.

Table 2.

Comparison of the prevalence of thyroid nodules in different subgroups for children from Shanghai, Haimen and Taizhou, China, in 2014

Characteristics No nodule Nodule(s)
n n (%) Solitary nodule (n (%)) Multiple nodules (n (%)) Total χ2, p Value* χ2, p Value†
All 1403 1144 (81.54) 83 (5.92) 176 (12.54) 259 (18.46)
Sex 3.95, 0.047 4.264, 0.119
 Male 739 617 (83.49) 37 (5.01) 85 (11.50) 122 (16.51)
 Female 664 527 (79.37) 46 (6.93) 91 (13.70) 137 (20.63)
Age (years) 9.11, 0.028 11.61, 0.071
 8 227 192 (84.58) 12 (5.29) 23 (10.13) 35 (15.42)
 9 461 359 (77.87) 34 (7.38) 68 (14.75) 102 (22.13)
 10 441 374 (84.81) 24 (5.44) 43 (9.75) 67 (15.19)
 11 274 219 (79.93) 13 (4.74) 42 (15.33) 55 (20.07)
Iodised salt consumption‡ 6.85, 0.009 12.46, 0.002
 No 485 380 (78.35) 26 (5.36) 79 (16.29) 105 (21.65)
 Yes 842 708 (84.09) 52 (6.18) 82 (9.74) 134 (15.91)
Urinary iodine (µg/L)§ 13.00, 0.005 18.65, 0.005
 ≤100 254 204 (80.31) 12 (4.72) 38 (14.96) 50 (19.69)
 100–200 508 400 (78.74) 31 (6.10) 77 (15.16) 108 (21.26)
 200–300 329 268 (81.46) 25 (7.60) 36 (10.94) 61 (18.54)
 >300 252 225 (89.29) 12 (4.76) 15 (5.95) 27 (10.71)
Area 142.11, <0.001 155.80, <0.001
 Shanghai 520 344 (66.15) 49 (9.42) 127 (24.42) 176 (33.85)
 Haimen 448 426 (95.09) 20 (4.46) 2 (0.45) 22 (4.91)
 Taizhou 435 374 (85.95) 14 (3.22) 47 (10.80) 61 (14.02)

*Comparison between participants with/without thyroid nodule(s).

†Comparison among participants without nodule/with solitary nodule/with multiple nodules.

‡A total of 60 missing: 36 (60.00%) were male and 24 (40.00%) were female.

§A total of 76 missing: 52 (68.42%) were male and 24 (31.58%) were female.

Based on BMI, 255 (18.17%) were overweight and 174 (12.40%) were obese. Girls were more likely to be overweight than boys, and the prevalence of overweight/obese decreased with age in both sexes (p trend: 0.033 for boys and 0.010 for girls). The prevalences of solitary and multiple nodules in overweight subjects were 3.53% (9/255) and 15.29% (39/255), while the corresponding prevalences were 20.48% (17/174) and 14.77% (26/174) in obese ones, respectively.

Multivariable analysis revealed significant associations between obesity and the risk of TN(s) (table 3). As compared with normal-weight children, obese children experienced a significantly higher risks of TN(s) (OR 1.82 (95% CI 1.22 to 2.70)). We observed a similar association of obesity with the risk of either solitary nodule or multiple nodules (table 4). When stratified by sex, only obese girls experienced an increased risk for multiple nodules (OR 2.10 (95% CI 1.03 to 4.31)), but the interaction of obesity with sex was not significant (p=0.494). Associations of multiple nodules with overweight (OR 1.87, 95% CI 1.07 to 3.29) and obesity (OR 2.00, 95% CI 1.05 to 3.78) were observed in children aged 8 or 9 years, but not in older ones. Overweight was not significantly associated with solitary TN in general, which might be due to small number of children with this thyroid condition. Overweight children had an increased risk for multiple TNs (OR 1.76, 95% CI 1.03 to 3.02) only in iodised salt consumers.

Table 3.

Multinomial logistic regression analysis of obesity and thyroid nodule(s) for children from Shanghai, Haimen and Taizhou, China, in 2014

Thyroid nodule(s)
No nodule Normal Overweight Obesity
N N OR N OR (95% CI)* N OR (95% CI)*
All subjects† 1144 168 48 43
 Model 1 1.00 1.11 (0.78 to 1.59) 1.58 (1.07 to 2.31)
 Model 2 1.00 1.00 (0.69 to 1.45) 1.82 (1.22 to 2.70)
 Model 3 1.00 1.04 (0.71 to 1.51) 1.71 (1.13 to 2.59)
Sex‡
 Male 576 80 1.00 14 0.83 (0.45 to 1.54) 17 1.39 (0.77 to 2.52)
 Female 512 79 1.00 29 1.21 (0.75 to 1.96) 20 2.10 (1.17 to 3.79)
Age (years)§
 8–9 519 76 1.00 27 1.37 (0.83 to 2.25) 25 1.87 (1.10 to 3.19)
 10–11 569 83 1.00 16 0.77 (0.43 to 1.38) 12 1.39 (0.70 to 2.75)
Iodised salt consumption¶
 Yes 708 81 1.00 28 1.20 (0.75 to 1.93) 25 1.62 (0.98 to 2.68)
 No 380 78 1.00 15 0.81 (0.43 to 1.50) 12 1.94 (0.92 to 4.09)

*95% confidence interval.

†Model 1, univariate analysis (n=1403); model 2, adjusted for sex, age, iodised salt consumption (n=1327); model 3, adjusted for sex, age, urinary iodine concentration (n=1343).

‡Adjusted for age and iodised salt consumption (n=1327).

§Adjusted for sex and iodised salt consumption (n=1327).

¶Adjusted for sex and age (n=1327).

Table 4.

Multinomial logistic regression analysis of obesity and solitary and multiple thyroid nodules for children from Shanghai, Haimen and Taizhou, China, in 2014

Normal Overweight Obesity
No nodule Solitary nodule Multiple nodules Solitary nodule Multiple nodules Solitary nodule Multiple nodules
N N OR N OR N OR (95% CI)* N OR (95% CI)* N OR (95% CI)* N OR (95% CI)*
All subjects† 1144 57 111 9 39 17 26
 Model 1 1.00 1.00 0.62 (0.30 to 1.26) 1.37 (0.92 to 2.03) 1.84 (1.04 to 3.25) 1.44 (0.91 to 2.30)
 Model 2 1.00 1.00 0.53 (0.25 to 1.13) 1.33 (0.88 to 2.03) 1.82 (0.99 to 3.36) 1.62 (0.98 to 2.70)
 Model 3 1.00 1.00 0.54 (0.25 to 1.16) 1.24 (0.82 to 1.88) 2.07 (1.16 to 3.71) 1.67 (1.03 to 2.70)
Sex‡
 Male 576 26 1.00 54 1.00 1 0.17 (0.02 to 1.28) 13 1.18 (0.61 to 2.26) 7 1.53 (0.63 to 3.71) 10 1.29 (0.62 to 2.70)
 Female 512 29 1.00 50 1.00 7 0.77 (0.33 to 1.82) 22 1.49 (0.86 to 2.59) 8 2.09 (0.89 to 4.89) 12 2.10 (1.03 to 4.31)
Age (years)§
 8–9 519 29 1.00 47 1.00 5 0.63 (0.24 to 1.68) 22 1.87 (1.07 to 3.29) 9 1.60 (0.71 to 3.57) 16 2.00 (1.05 to 3.78)
 10–11 569 26 1.00 57 1.00 3 0.46 (0.14 to 1.55) 13 0.95 (0.50 to 1.82) 6 2.05 (0.80 to 5.25) 6 1.05 (0.43 to 2.60)
Iodised salt consumption¶
 Yes 708 35 1.00 46 1.00 5 0.48 (0.18 to 1.27) 23 1.76 (1.03 to 3.02) 12 1.76 (0.88 to 3.54) 13 1.50 (0.78 to 2.90)
 No 380 20 1.00 58 1.00 3 0.59 (0.17 to 2.08) 12 0.88 (0.45 to 1.75) 3 1.84 (0.50 to 6.79) 9 1.97 (0.86 to 4.48)

*95% confidence interval.

†Model 1, univariate analysis (n=1403); model 2, adjusted for sex, age, iodised salt consumption (n=1327); model 3, adjusted for sex, age, urinary iodine concentration (n=1343).

‡Adjusted for age and iodised salt consumption (n=1327).

§Adjusted for sex and iodised salt consumption (n=1327).

¶Adjusted for sex and age (n=1327).

Figure 2 presents multivariate-adjusted ORs and 95% CIs for solitary and multiple TNs associated with the quintiles of BSA, WC, BMI and WHR, respectively. After adjustment for sex, age and iodised salt consumption status, BSA and WC were positively related to the risks of solitary and multiple nodule(s) (p values for trend for all the nodules together were 0.0001 and <0.0001, respectively). As compared with children in the lowest quintile, the ORs of solitary and multiple nodules were 2.45 (95% CI 1.24 to 4.87) and 2.76 (95% CI 1.54 to 4.97) for those in the highest quintile of BSA and 3.46 (95% CI 1.54 to 7.80) and 2.18 (95% CI 1.27 to 3.74) for those in the highest quintile of WC, respectively. The interaction between BSA and sex on TNs was not statistically significant (p interaction: 0.785 for solitary nodule and 0.600 for multiple nodules).

Figure 2.

Figure 2

Associations of different physical measurements (body surface area, waist circumference, body mass index and waist–hip ratio) with thyroid nodule(s) for children from Shanghai, Haimen and Taizhou, China, in 2014.

The results for BMI and WHR were less consistent. BMI was positively associated with the risk of multiple nodules (p trend=0.005), while WHR showed no association with either solitary or multiple nodules.

Discussion

In this large cross-sectional study of children living in iodine-sufficient areas in East China, we observed a high prevalence of TNs and positive associations of obesity with both solitary and multiple TNs. Among several anthropometric measurements, BSA and WC were related to the risks for both solitary and multiple TNs. These findings were generally consistent across sex groups and independent of iodised salt consumption status.

TN(s) is common in adults, and its impact on thyroid cancer risk is still unclear.16 The prevalence of incidental TNs detected by ultrasound examinations is high in adults (close to 50%) as well as in iodine-deficient countries.3–5 However, few studies have investigated the prevalence and the spectrum of appearance of ultrasound-detected findings in children. TNs were identified in 1.65% of children aged 3–18 years in three Japanese prefectures, and the prevalence increased with age with a female predominance.32 The information released by Fukushima Prefecture indicated that 2014 (1.15%) of 75 216 Japanese children aged 0–18 had TNs.33 Avula et al conducted a retrospective analysis in 287 Canadian children (mean age=6.2) and detected only 1 child with multiple TNs but 52 (18%) children with thyroid abnormalities.34 In healthy Greek children living in an iodine-replete area, one or more nodules were observed in 5.1% of them.35 For 2410 children aged 6–17 years living in Hangzhou, China, TNs were detected in 10.66% of them.36 These results showed much lower frequencies than those observed in the current study, in which TNs existed in 18.46% of 1433 Chinese children with little age variations and sex variations. Influencing factors include age composition, interobserver variation, iodine intake, socioeconomic status and individual and/or family history, as well as detection sensitivity and image quality of ultrasound machine.32

TN has multiple known risk factors, including demographic parameters, clinical history, age, sex,6–8 iodine deficiency3 and potentially milk consumption.36 The association between TN(s) and obesity has been explored mostly in adults with inconsistent results.37 38

Obesity is a risk factor for several chronic conditions, as well as goitre in adults.39 Its impact on TNs has also been investigated by using different anthropometric parameters in adults. Among various parameters, BMI was most frequently used as a measure of general adiposity. It has been increasingly recognised that the adverse effects of obesity relate to the amount and to the distribution of excess body fat. Therefore, the use of BMI alone to infer health risks in Asians may underestimate the detrimental health effects of excess adiposity.40 WHR and WC were good proxy measures of central adiposity. It has been suggested that WC is a better marker for total body adiposity than it is for visceral fat.41 Another study has shown that both WC and BMI appear to perform equally well for estimating children and adolescents’s total adiposity.42 BSA is a better indicator of the circulating blood volume, oxygen consumption and basal energy expenditure than BMI37 and has been shown to be the best independent predictor of the thyroid volume in both sexes.

Several studies have found significant associations between measures of obesity and the risk of TNs. For example, a study conducted in Hangzhou, China, observed a prevalence of TN being 34.97% (33.97 for men and 36.92% for women) and great WC as a risk factor for new TN in this iodine-adequate area.2 Similar trends were observed for females and males, but the association was not statistically significant in men,2 which was similar to our findings in children. Another study of postmenopausal women also revealed that WC and BMI were associated with TNs.43 Large BMI was associated with nodule growth among older patients with multiple nodules and larger dominant nodules.17 A study conducted by Shin et al linked thyroid nodular disease to WC for males and glycated haemoglobin for females,44 suggesting potential sex disparity. The presence of insulin resistance was associated with larger thyroid gland volume and an increased prevalence of TNs,45 46 which might be explained by obesity-related subclinical inflammation and an associated increase in levels of insulin-like growth factor-1.45 However, another study yielded conflicting results, which suggested that adult patients with normal weight or overweight based on BMI tended to have an increased risk of TNs, as compared with underweight or obese people.38 Evidence in children had been relatively limited.

The prevalence of obesity and overweight in our study population was slightly higher than that in students from four Chinese megacities (25.6%)47 but lower than urban students of similar age groups in the National Surveys on Chinese Students' Constitution and Health (37.0% for overweight and 20.3% for obesity).48 Our findings of increased risk for TNs in obese children are generally consistent with those in obese adults of other studies. The association of BSA with thyroid volume in children has been well established,35 while its relation to TNs has been seldom explored. Kim et al38 examined 7763 healthy Korean adults and observed a significantly smaller BSA in those with TNs compared with the others, which was opposite to our findings. Considering the great difference in BSA between adults and children, it needs to be cautious to generalise the results to children.16 Xu et al36 conducted a cross-sectional study in Hangzhou, China, and reported an OR of 2.97 (95% CI 1.85 to 4.77) for TNs for children with average BSA or above as compared with those with less than average BSA. However, they did not collect the information on waist and hip circumferences and number of TNs. Therefore, it was not possible to determine different associations between WC, WHR and different kinds of nodules in that study. The potential interactive effects of iodised salt consumption and sex on the association between overweight and multiple nodules also need further investigations with a larger sample size.

The strengths of our study include large sample size, directly measured thyroid ultrasonography and anthropometric measurements following a standardised protocol and the abilities to distinguish solitary and multiple nodules and to adjust for household iodised salt consumption status. Our study has several limitations. First, we did not have any information on thyroid function. Therefore, we were unable to further search potential mechanisms that might explain the observed associations. Second, there were no information on the amount of salt and milk consumption. In the current study, the number of children with solitary or multiple nodules was small in some categories. In addition, the cross-sectional design prevents us from making causal inferences.

Conclusion

In this cross-sectional study of a relatively lean children population, we found that elevated levels of general or abdominal adiposity, measured by BMI, BSA and WC, were associated with a significant increase in the risk of TN(s), especially multiple nodules in girls and solitary nodule in boys. Our findings, along with those observed from adult populations, emphasise the importance of preventing excess adiposity for primary prevention of TNs.

Supplementary Material

Reviewer comments
Author's manuscript

Footnotes

Contributors: NW, HF, CF, PH, MS, QZ and QJ contributed to the study design; NW, HF, CF, PH, MS, FJ, QZ and QJ contributed to data acquisition and collection; NW, QZ and YC contributed to data analysis and interpretation; NW, QZ and YC drafted the manuscript; all authors contributed to the preparation of the final document, read and approved the final manuscript.

Funding: This work was supported by the Chinese National Natural Science Foundation (number 81602806), Shanghai Municipal Commission of Health and Family Planning (number 20144Y0104) and Shanghai Key Discipline Construction Project of Shanghai Municipal Public Health (number 15GWZK0801).

Competing interests: None declared.

Patient consent: Parental/guardian consent obtained.

Ethics approval: The study was approved by the ethical review board of the School of Public Health of Fudan University (#2012-03-0350S).

Provenance and peer review: Not commissioned; externally peer reviewed.

Data sharing statement: No additional data are available.

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