The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid

Abstract

Objectives

To evaluate the association between thyroid autoantibodies and abnormalities in thyroid function and structure, and to investigate any risk factors.

Methods

A cross-sectional survey was undertaken in Chengdu residents ≥18 years with no previous thyroid disease. The study participants provided demographic and clinical data. Thyroid function and serum concentrations of the thyroid autoantibodies antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) were measured.

Results

A total of 1334 subjects were included in this study. The prevalence of TPOAb and TgAb positivity was significantly higher in female than in male subjects. The prevalence of thyroid autoantibodies in those with subclinical hypothyroidism and clinical hyper- and hypothyroidism was significantly greater than in euthyroid subjects. The concentration of TPOAb and TgAb in subjects with both TPOAb and TgAb was significantly higher than in those who exhibited only one type of thyroid autoantibody. Using multivariate logistic regression analysis, female sex, thyroid volume, thyroid hypo- and heteroechogenicity were found to be risk factors for the presence of autoantibodies.

Conclusions

Thyroid autoantibodies were common in the general population. Women with thyroid enlargement, hypoechogenicity and heteroechogenicity might benefit from routine screening for thyroid autoantibodies and thyroid function.

Keywords

Antithyroperoxidase antibody antithyroglobulin antibody thyroid diseases thyroid autoantibodies risk factors epidemiology study

Introduction

Antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) are common thyroid autoantibodies in patients with autoimmune thyroid disease.¹ Studies have demonstrated that the serum presence of thyroid autoantibodies is correlated with the presence of lymphocytic infiltration and the severity of histological thyroiditis.^2,3 However, one or both of these two antibodies are frequently detected in the general population.⁴ A cross-sectional survey conducted in areas of iodine deficiency in Denmark, in populations with no current or prior thyroid disease, showed that the prevalence of serum positivity for TPOAb and TgAb were 13.1% and 13.0%, respectively.⁴ The National Health and Nutrition Examination Survey III (NHANES III) study reported that TPOAb and TgAb were present in 11.3% and 10.4%, respectively, of a disease-free population.⁵ The prevalence of thyroid autoantibodies varies between populations and is influenced by many factors including as heredity and the environment.^6,7 Environmental factors such as iodine nutrition, age, sex and smoking habits might influence thyroid function, thyroid autoantibodies and thyroid structure.^8–11 Although several cross-sectional surveys have reported the prevalence of thyroid autoantibodies,^4,5 studies in China, especially in the south-western region, have rarely explored the prevalence of these thyroid autoantibodies since universal salt iodization began in 1996.

This cross-sectional survey investigated the prevalence of serum thyroid autoantibodies, and evaluated the association between their presence and abnormalities in thyroid function and structure, in a Chinese population from Chengdu, China, an area that was previously reported to be iodine sufficient.¹²

Subjects and methods

Study participants

A cross-sectional survey was conducted in a Chengdu community based at Yulin Community Health Service Centre, Wuhou District, Chengdu, China, which is one of 10 cities in China undergoing an epidemiological investigation on thyroid disease (conducted by the Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China). A total of 1500 residents ≥18 years of age who had lived in Chengdu for ≥5 years were invited to participate in this study, using an age- and sex-stratified cluster sampling technique. The study sample was randomly selected by the numbers of residential buildings in this Chengdu community. The cross-sectional survey was undertaken between December 2009 and May 2010. The exclusion criteria were as follows: pregnant or postpartum women within 1 year; subjects taking glucocorticoids, dopamine ordobutamine; subjects taking antiepileptic drugs (e.g. phenytoin, carbamazepine); subjects with adrenocortical insufficiency, renal insufficiency, other serious systemic disease or chronic wasting disease; subjects who received amiodarone or an iodine-containing contrast agent within the previous 6 months. The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University, Chengdu, China. All of the participants in this study provided written informed consent.

Methods

A questionnaire was designed by the Chinese Society of Endocrinology specifically for this study in order to obtain general personal information, including sex, age, smoking history, history of thyroid disease and intake of iodine supplements. The subjects who were enrolled in this study attended a clinical examination with blood-sample collection at Yulin Community Health Service Centre, Wuhou District, Chengdu. Participants completed their questionnaires at home prior to the clinical examination. Smoking status was classified into three categories: nonsmoker, occasional smoker (<1 cigarette per day) and frequent smoker (≥1 cigarette per day). Each subjects’ height, weight and blood pressure was measured by nurses using standardized procedures. Venous blood (3 ml) was collected after an overnight fast. After standing for 1.5 h, the blood sample was centrifuged at 704 g for 5 min at room temperature in a medical low-speed centrifuge (Beijing Medical Centrifuge Factory, Beijing, China). The serum was separated and stored at −20℃ until further analysis.

Thyroid ultrasonography was performed by trained technicians using ultrasonography equipment with a 7.5 MHz probe (LOGIQ® 500; GE Healthcare China, Beijing, China). The volume of each thyroid lobe was calculated using the formula: V (ml) = 0.479 × width × length × thickness.¹³ The thyroid volumes consisted of the sum of the volumes of the two lobes. Diameters of any thyroid nodules that were identified were measured and recorded. The thyroid interecho classifications included isoechogenicity, hyperechogenicity, hypoechogenicity and heteroechogenicity.¹²

Laboratory methods

Thyroid function and thyroid autoantibodies were measured using Roche chemiluminescence immunoassay kits (thyroid-stimulating hormone [TSH]: kit no. 11731459122; free triiodothyronine [FT3]: kit no. 03051986190; free thyroxine [FT4]: kit no. 11731297122; TgAb: kit no. 04738578190; TPOAb: kit no. 11820818122) and a Roche cobas® 6000 (e601 module) analyser (Roche, Mannheim, Germany). The intra- and interassay coefficients of variation were all <5%. The TPOAb, TgAb, and TSH levels were measured in each study participant. The serum TSH concentration was used to evaluate thyroid function. If TSH was <0.71 mIU/l, the FT4 and FT3 levels were also measured in the same sample. If TSH was >6.25 mIU/l, then only the FT4 level was measured. The normal reference ranges of FT3, FT4 and TSH were 3.1–6.8 pmol/l, 12.0–22.0 pmol/l and 0.71–6.25 mIU/l, respectively. The normal negative references for TPOAb and TgAb were 34 IU/ml and 115 IU/ml, respectively.¹² The minimum detectable concentrations were 0.005 mIU/l for TSH, 0.400 pmol/l for FT3, 0.300 pmol/l for FT4, 5 IU/ml for TPOAb and 10 IU/ml for TgAb. The reference range of TSH was based on a thyroid epidemiological survey of 10 cities in China and has been demonstrated to be suitable for Chinese populations.¹²

Diagnostic criteria for thyroid disease

Clinical hypothyroidism was diagnosed when the serum TSH concentration was >6.25 mIU/l and the serum FT4 was <12.0 pmol/l. Subclinical hypothyroidism was diagnosed when the serum TSH concentration was >6.25 mIU/l and the serum FT4 was within the normal range. Clinical hyperthyroidism was diagnosed when the serum TSH concentration was <0.71 mIU/l and the serum FT4 was >22.0 pmol/l and/or the FT3 concentration was >6.8 pmol/l. Subclinical hyperthyroidism was diagnosed when the serum TSH concentration was <0.71 mIU/l and the serum FT4 and FT3 were within normal ranges. Thyroid autoantibodies were regarded as positive when the TPOAb level was >34 IU/ml and/or the TgAb level was >115 IU/ml.

Goitre was defined as a thyroid volume >14.4 ml for women and >18.8 ml for men. This definition was derived from the mean (+2 SD) thyroid volume in 597 subjects (315 male and 282 female) with no personal or family history of thyroid disease, with no thyroid autoantibodies, and with an undetected goitre or nodules using B-mode ultrasonography.¹⁴

Statistical analyses

All statistical analyses were performed using the SPSS® statistical package, version 16.0 (SPSS Inc., Chicago, IL, USA) for Windows®. Normally distributed data were expressed as mean ± SD. Not-normally distributed data were expressed as the median and interquartile range (Q1–Q3). Body mass index (BMI) was calculated using the formula: BMI = weight (kg)/height (m²). Nonparametric statistical tests (Mann–Whitney U-test or Kruskal–Wallis test) and parametric statistical tests (Student’s t-test) were used when appropriate for continuous variables. χ²-test was used for noncontinuous variables. Differences in the prevalence of thyroid autoantibodies were tested using a χ²-test and the χ² trend test if necessary. Risk factors were evaluated using univariate and multivariate logistic regression analyses. Apart from the TPOAb and/or TgAb levels, the following variables were included in the models: age, sex, smoking status, BMI, TSH concentration, thyroid volume, thyroid nodules and thyroid echogenicity. The level of significance was set at 5%. A P-value <0.05 was considered statistically significant.

Results

A total of 1500 residents >18 years of age who had lived in Chengdu for ≥5 years were invited to participate in this study using an age- and sex-stratified cluster sampling technique. A total of 1334 subjects (730 female and 604 male) with no history of thyroid disease who completed the survey were included in this analysis. The mean ± SD age of female and male subjects were 46.4 ± 14.6 years and 44.9 ± 15.8 years, respectively. A total of 211 of 1334 (15.8%) of the study population had detectable TPOAb and/or TgAb. TPOAb alone was positive in 154 of 1334 (11.5%) participants and TgAb alone was positive in 140 of 1334 (10.5%) participants. TPOAb and TgAb were detected together in 6.2% (83/1334) of the study participants. The demographic and clinical characteristics of the study participants are presented in Table 1. Female subjects were significantly more likely to be positive for thyroid autoantibodies than male subjects (P < 0.001). In participants with thyroid antibodies, the serum median TSH concentration was elevated compared with participants without antibodies (TPOAb, P = 0.001; TgAb, P = 0.003; TPOAb and/or TgAb, P = 0.001; TPOAb and TgAb, P = 0.001). For female subjects, the numbers of nonsmokers, occasional smokers and frequent smokers were 704, 18 and eight, respectively. The numbers of male subjects who were nonsmokers, occasional smokers and frequent smokers were 318, 65 and 221, respectively. The prevalence of positive thyroid autoantibodies (TPOAb and/or TgAb) among nonsmokers was 18.2% (186/1022); and the prevalence of positive thyroid autoantibodies (TPOAb and/or TgAb) among smokers (occasional and frequent) was 8.0% (25/312). Smokers (occasional and frequent) had a significantly lower prevalence of positive thyroid autoantibodies (TPOAb and/or TgAb) than nonsmokers (P < 0.001).

Table 1.

Demographic and clinical characteristics of participants aged ≥18 years (n = 1334), with no previous thyroid disease, in a cross-sectional survey that investigated the prevalence of serum thyroid autoantibodies and evaluated the association between such antibodies and abnormalities in thyroid function and structure.

Thyroid autoantibody subgroup	n	Age, years	Statistical significance^a	Sex		Statistical significance^a	TSH, mIU/l	Statistical significance^a	BMI, kg/m²	Statistical significance^a
Thyroid autoantibody subgroup	n	Age, years	Statistical significance^a	Male	Female	Statistical significance^a	TSH, mIU/l	Statistical significance^a	BMI, kg/m²	Statistical significance^a
TPOAb:
+	154	48.8 ± 15.1	P = 0.009	46 (29.9)	108 (70.1)	P < 0.001	3.5 (2.0–3.7)	P = 0.001	23.3 ± 3.6	NS
−	1180	45.4 ± 15.1		558 (47.3)	622 (52.7)		2.6 (1.8–3.7)		22.8 ± 3.2
TgAb:
+	140	48.0 ± 15.1	NS	31 (22.1)	109 (77.9)	P < 0.001	3.0 (2.0–5.0)	P = 0.003	22.8 ± 3.5	NS
−	1194	45.5 ± 15.2		573 (48.0)	621 (52.0)		2.6 (1.8–3.7)		22.9 ± 3.3
TPOAb and/or TgAb:
+	211	48.5 ± 15.0	P = 0.004	55 (26.1)	156 (73.9)	P < 0.001	3.2 (1.9–4.6)	P = 0.001	23.1 ± 3.8	NS
−	1123	45.2 ± 15.1		549 (48.9)	574 (51.1)		2.6 (1.8–3.7)		22.8 ± 3.2
TPOAb and TgAb:
+	83	48.1 ± 15.4	NS	22 (26.5)	61 (73.5)	P < 0.001	3.8 (2.0–5.8)	P = 0.001	22.9 ± 3.0	NS
−	1251	45.6 ± 15.1		582 (46.5)	669 (53.5)		2.6 (1.8–3.8)		22.9 ± 3.3

Data presented as mean ± SD, n of subjects (%) or median and interquartile range (Q1–Q3).

Nonparametric statistical tests (Mann–Whitney U-test or Kruskal–Wallis test) and parametric statistical tests (Student’s t-test) were used when appropriate for continuous variables; χ²-test was used for noncontinuous variables.

TSH, thyroid stimulating hormone; TPOAb, antithyroperoxidase antibody; TgAb, antithyroglobulin antibody; NS, no statistically significant difference (P 0.05).

The median TPOAb and TgAb concentrations in the 1334 subjects were 162.6 IU/ml (interquartile range 65.1–503.1) and 396.5 (interquartile range 197.1–715.5) IU/ml, respectively. Men exhibited a significantly higher median concentration of TgAb than women (593.0 IU/ml versus 368.6 IU/ml, respectively; P = 0.003); but there was no significant difference in the median concentration of TPOAb between men and women (141.8 IU/ml versus 169.0 IU/ml, respectively). The median concentration of TPOAb in the participants with both TPOAb and TgAb present was significantly higher than that of the participants with only one type of thyroid autoantibody; this significance was also found in the median concentration of TgAb (TPOAb 247.5 IU/ml versus 92.6 IU/ml, respectively, P < 0.001; TgAb 447.5 IU/ml versus 340.1 IU/ml, respectively, P = 0.02).

For the purpose of these analyses, the 1334 study participants were divided into five groups based on their thyroid function: euthyroidism (n = 1209; 90.6%), clinical hyperthyroidism (n = 13; 1.0%), subclinical hyperthyroidism (n = 26; 1.9%), clinical hypothyroidism (n = 12; 0.9%) and subclinical hypothyroidism (n = 74; 5.5%). The prevalence of thyroid autoantibodies (TPOAb and/or TgAb) was 13.8% (167/1209), 83.3% (10/12) and 76.9% (10/13) in subjects with euthyroidism, clinical hypothyroidism and clinical hyperthyroidism, respectively. Study participants with euthyroidism had a significantly lower prevalence of thyroid autoantibodies (TPOAb, TgAb, TPOAb and TgAb, TPOAb and/or TgAb) than those with clinical hyper-/hypothyroidism or subclinical hypothyroidism (all P < 0.05; data not shown). A significant difference in the prevalence of both TPOAb and TgAb positivity was found between the euthyroidism and subclinical hyperthyroidism groups (TPOAb and TgAb, P = 0.039; data not shown). The prevalence of thyroid nodules in the 1334 study participants was 16.9% (225/1334) and no significant differences were found using the subgroup analysis.

Using a univariate logistic regression model, age, female sex, being a frequent smoker, TSH level, thyroid volume, thyroid goitre, hypoechogenicity and heteroechogenicity were found to be risk factors for thyroid autoantibody positivity (Table 2). In the multivariate logistic regression analysis, the final model retained the following variables: female sex, thyroid volume, hypoechogenicity and heteroechogenicity. The risk of TPOAb positivity increased significantly with an elevated TSH concentration, however, the risk was not significant between TgAb and the TSH level.

Table 2.

Logistic regression analysis to assess the risk of the presence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) in a study population aged ≥18 years (n = 1334), with no previous thyroid disease.

Characteristic	TPOAb		TgAb
Characteristic	OR (95% CI)	Statistical significance	OR (95% CI)	Statistical significance
Univariate analysis
Age, years	1.02 (1.00, 1.03)	P = 0.012	1.01 (1.00, 1.03)	P = 0.032
Female	1.97 (1.31, 2.97)	P = 0.001	3.84 (2.35, 6.28)	P < 0.001
BMI, kg/m²	1.07 (1.02, 1.12)	P = 0.011	0.99 (0.93, 1.05)	NS
Thyroid nodules	1.07 (0.64, 1.77)	NS	1.39 (0.85, 2.28)	NS
Smoking status:
Frequently	0.52 (0.29, 0.95)	P = 0.033	0.15 (0.06, 0.42)	P < 0.001
Occasionally	0.70 (0.30, 1.66)	NS	0.46 (0.16, 1.27)	NS
TSH, mIU/l	1.23 (1.07, 1.42)	P = 0.005	1.21 (1.04, 1.41)	P = 0.012
Thyroid volume	1.08 (1.04, 1.11)	P < 0.001	1.07 (1.03, 1.10)	P < 0.001
Thyroid echogenicity:
Hypoecho	6.03 (3.64, 9.99)	P < 0.001	7.30 (4.42, 12.06)	P < 0.001
Heteroecho	7.43 (3.62, 15.24)	P < 0.001	2.87 (1.16, 7.13)	P = 0.023
Hyperecho	0.000^a	NS	0.000^a	NS
Thyroid goitre	2.67 (1.68, 4.26)	P < 0.001	2.13 (1.28, 3.53)	P = 0.003
Multivariate analysis
Female	1.90 (1.22, 2.96)	P = 0.005	3.68 (2.20, 6.17)	P < 0.001
TSH, mU/l	1.22 (1.04, 1.42)	P = 0.014	1.17 (0.99, 1.34)	NS
Thyroid volume	1.09 (1.05, 1.14)	P < 0.001	1.07 (1.03, 1.11)	P < 0.001
Thyroid echogenicity:		P < 0.001
Hypoecho	4.68 (2.73, 8.03)	P < 0.001	5.04 (2.97, 8.56)	P < 0.001
Heteroecho	6.88 (3.22, 14.69)	P < 0.001	2.41 (0.94, 6.17)	NS
Hyperecho	0.000^a	NS	0.000^a	NS

The output from the SPSS® statistical package (version 16.0) was 0.000 for OR, 0.000 for the lower 95% CI, and the higher 95% CI was infinitely large.

OR, odds ratio; CI, confidence interval; BMI, body mass index; TSH, thyroid stimulating hormone; NS, no statistically significant difference (P ≥ 0.05).

The numbers of subjects classified as having isoechogenicity, hyperechogenicity, heteroechogenicity and hypoechogenicity were 1157, 11, 48 and 118, respectively. Study participants with thyroid hypoechogenicity were divided into five groups according to their TPOAb and TgAb concentrations. Individuals who were negative for both TPOAb and TgAb were placed in group 0; groups 1–4 were divided by quartiles of thyroid autoantibody-positive concentrations. The hypoechogenicity subgroup analysis showed that regardless of whether the subject was TgAb positive or not, the prevalence of thyroid hypoechogenicity increased with increasing concentrations of TPOAb (TgAb positive, P < 0.001, χ² trend test; TgAb negative, P < 0.001, χ² trend test; data not shown). In addition, there was a trend towards an increased prevalence of thyroid hypoechogenicity with an elevated concentration of TgAb, regardless of the TPOAb concentration (TPOAb negative, P < 0.001, χ² trend test; TPOAb positive, P = 0.001, χ² trend test; data not shown). In total, a trend towards an increased prevalence of thyroid hypoechogenicity with elevated levels of TPOAb and TgAb was observed in this study (TPOAb, P < 0.001, χ² trend test; TgAb, P < 0.001, χ² trend test; data not shown).

Discussion

Consistent with previous research, in the present study, thyroid autoantibodies were significantly more prevalent in female than in male participants in a cohort (n = 1334) with no history of thyroid disease.^4,5,15 Furthermore, the current study detected a significantly greater serum median TSH concentration in tparticipants who were positive for thyroid autoantibodies compared with those who were negative. A significant association was demonstrated between an elevated TSH level and the presence of thyroid autoantibodies.¹⁶ Although this current cross-sectional study did not show a risk for the participants with positive thyroid autoantibodies developing either subclinical or clinical hypothyroidism, such a progression has been reported in a longitudinal study.¹⁷ In addition, for euthyroid individuals with positive autoantibodies at baseline, those who developed hypothyroidism in the follow-up study had significantly higher baseline TSH levels than those who remained euthyroid.¹⁵ This current study also found that, in serum containing both TPOAb and TgAb, the median concentrations of autoantibodies were significantly higher than in serum containing only one type of autoantibody. The presence of one antigen might enhance the concentration of the other antigen in the immune system, or the reactivity of the immune system against thyroid antigens when both autoantibodies are present may be enhanced.

In the current study, the prevalence of thyroid autoantibodies was as high as 83.3% and 76.9% in subjects with clinical hypothyroidism and clinical hyperthyroidism, respectively. Significant differences were observed in the prevalence of positive thyroid autoantibodies between euthyroid subjects and those with thyroid dysfunction. Previous studies observed that thyroid autoantibodies were involved in thyroid abnormalities.^18–20 The presence of TPOAb and TgAb was associated with lymphocytic infiltration in NOD.H-2h4 mice.²¹ This association suggests that TPOAb and TgAb may play an important role in the pathogenesis of thyroid abnormalities. Several studies have suggested that TPOAb could induce antibody-dependent cell-mediated cytotoxicity, and that concentrations of TPOAb might correlate with severity of thyroid lymphocytic infiltration, regardless of the presence or absence of hypothyroidism.^18,22,23 The antibody to thyroglobulin (Tg) could facilitate the formation of complement-activating Tg/TgAb complexes.²⁴ Patients with high-avidity TgAb might be at a high risk of developing subclinical and clinical hypothyroidism.²⁵ However, the positive rate for thyroid TPOAb and/or TgAb was 13.8% in euthyroid subjects in the present study. A longitudinal study in China found that the prevalence of abnormal thyroid function, especially hypothyroidism, in euthyroid subjects with positive antibodies at baseline, either alone or combined (TgAb and/or TPOAb), was much higher than in euthyroid subjects who were antibody negative after 5 years.¹⁵ Populations positive for thyroid autoantibodies may be at a high risk of abnormal thyroid function.¹⁷ A routine examination of thyroid function in individuals with positive thyroid autoantibodies may be necessary and is suggested, based on these current findings.

The univariate and multivariate logistic analyses in the present study revealed that female sex was a risk factor for TPOAb and TgAb positivity. A previous study showed that presence of thyroid autoantibodies was significantly associated with female sex.¹⁶ Female sex was reported to be a risk factor for TgAb positivity.¹⁵ Cross-sectional²⁶ and longitudinal²⁷ studies found that the prevalence of thyroid autoantibodies was higher in subjects with thyroid goitres than in those without thyroid goitres. In the Whickham Survey follow-up study,¹⁷ patients who had developed a goitre had also developed thyroid autoantibodies. However, findings of the current study showed that thyroid goitres were not in the final multivariate analysis. In addition, thyroid volume was a risk factor for the presence of thyroid autoantibodies in the current study, both in the univariate and multivariate logistic regression analyses. A study undertaken in people with elevated TSH demonstrated that there was a strong association between thyroid autoantibodies and an enlarged thyroid.²⁸ In hypothyroidism patients, a high level of autoantibodies (TPOAb and/or TgAb) was significantly associated with thyroid enlargement: patients with thyroid enlargement had the highest values of both TPOAb and TgAb.²⁹ In another study, antibody-positive subjects had larger thyroid volumes than control subjects.³⁰ Various associations may exist between thyroid autoantibodies, thyroid volume and goitres. TgAb formation might reduce the level of Tg, and low Tg levels maximize growth-promotion activity and induction of the apical iodide transporter, which stimulates follicular cell growth.³¹ In addition, the co-ordinated actions of TSH and insulin/insulin-like growth factor-1 signalling might regulate thyroid cell growth.^32,33

Thyroid hypoechogenicity was reported to be involved in thyroid autoimmune inflammation and lymphocytic infiltration.³⁴ Thyroid hypo- and heteroechogenicity were found to be highly indicative of autoimmune thyroiditis.³⁵ In the current study, thyroid hypoechogenicity and heteroechogenicity were risk factors for thyroid autoantibody positivity. The prevalence of hypoechoic thyroid increased with elevated concentrations of TPOAb and TgAb. Hypoechogenicity and heteroechogenicity were associated with significantly higher levels of TPOAb activity and were indicative of a high level of autoimmune inflammatory activity of the thyroid gland.³⁶ A close relationship between the heteroechogenicity of the thyroid gland and TPOAb was reported in euthyroid patients with Hashimoto’s thyroiditis before the heteroechogenicity became distinguishable from normal thyroid glands.³⁷

How smoking affects thyroid autoimmunity remains controversial. The NHANES III study found that the prevalence of thyroid autoantibodies was lower in smokers than in nonsmokers.⁵ A significant negative association was observed between smoking and the presence of TPOAb and TgAb.³⁸ Furthermore, a prospective study reported that smoking cessation might increase the risk of TPOAb and TgAb positivity.³⁹ Similarly, the current study demonstrated that the prevalence of TPOAb and/or TgAb positivity was lower in smokers (occasional and frequent) than in nonsmokers. In addition, using univariate logistic regression analysis, being a frequent smoker was a protective factor for positive TPOAb and TgAb (TPOAb: odds ratio [OR] 0.52, P = 0.033; TgAb: OR 0.15, P < 0.001). However, smoking was not in the final model of the multivariate logistic analysis. In the current study, BMI was a risk factor for TPOAb positivity, but not for TgAb, in the univariate logistic regression analysis; however, BMI was not in the final model of the multivariate analysis. The prevalence of positive thyroid autoantibodies was increased in obese children, particularly in those with elevated TSH.⁴⁰ Obese patients had a higher frequency of antithyroid antibodies than control patients.⁴⁰ The prevalence of TPOAb positivity was greater in the obese group in a cross-sectional study undertaken in 165 obese and 118 lean subjects.⁴¹ This finding may be due to increased antigen presentation by amplified thyroid stimulation, or it may be associated with another factor, such as the leptin level.⁴¹ Future studies are needed to understand how obesity might enhance the risk of thyroid autoimmunity.

The current investigation had a number of limitations. First, the study did not include subjects <18 years of age. Secondly, the study was cross-sectional and hence did not investigate individual changes over time. Thirdly, laboratory tests assessing FT4 and/or FT3 were only performed in subjects with abnormal TSH levels.

In conclusion, female sex, thyroid volume, thyroid hypoechogenicity and heteroechogenicity were risk factors for the presence of the thyroid autoantibodies TPOAb and TgAb. Thyroid autoantibodies were detected in subjects with thyroid dysfunction and in those who were euthyroid. An increased prevalence of thyroid hypoechogenicity correlated with elevated levels of TPOAb and TgAb. The presence of thyroid autoantibodies was indicative of autoimmune thyroiditis. Smoking may be a protective factor for the presence of TPOAb and TgAb. Women with thyroid enlargement, thyroid hypoechogenicity and heteroechogenicity would benefit from routine evaluation of thyroid autoantibody status and thyroid function.

Footnotes

Authors' contributions

Yue-Rong Yan and Xi-Lian Gao contributed equally to this work. Hui Huang and Nan-Wei Tong conceived of the project concept, assisted with the data interpretation, and helped write and modify the manuscript together.

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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