Association between lifestyle and thyroid dysfunction: a cross-sectional epidemiologic study in the She ethnic minority group of Fujian Province in China

The She ethnic minority is one of the smaller ethnic populations in China. Confining our study to such a cohort with relatively homogenous genetic and general environmental background allows us to better isolate lifestyle factors from the genetic components of the disease, as well as minimize the effect of other hidden environmental variables. The study is part of an epidemic survey of the diabetes in the She ethnic minority group of Fujian Province. We recruited participants by advertising and phone calls made by the community workers. Subjects registered were permanent residents of the Fujian province She reservation area, aged 20–80 years. A multistage, stratified, cluster random sampling method was used in order to select a representative sample. A total of 5385 She ethnic residents were enrolled in the survey and 5154 subjects who had results of TSH and TPOAb levels were collected in our study. The study was approved by the Ethics Committee of Fujian Medical University. We had complied with the Declaration of Helsinki Ethical Principles for medical research involving human subjects [13]. All the participants signed informed consent authorized by the Chinese Medical Association before data collection.

The role of subjects in this study were participants. They were not involved in the recruitment or conduction of the study. After the completion of the study, we sent each participant a letter describing the detailed results of their own physical examinations and lab tests free of charge. If the lab tests or physical examinations showed abnormal results, we informed the participants by phone calls and advised them to go to the clinic for appropriate further examination and treatments.

Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared (kg/m²). Blood pressure was measured twice in the sitting position by manual sphygmomanometer on the right arm after at least 5 min of rest, and the mean of the two readings was used for analysis. All of the staffs conducting the physical examinations completed a training program of the entire study protocol before they began to collect data.

Serum TSH was assessed using an electrochemiluminescence (Nichols Institute Diagnostics, San Juan Capistrano, CA, USA). The working range for this method was 0.01–100 mIU/L. Serum TPOAb were measured with a highly sensitive, direct RIA system (Kronus, San Clemente, CA, USA). The reference range of TPOAb was ≤35 IU/ml. Serum triglycerides (TG). Total cholesterol (TC) and high–density lipoprotein cholesterol (HDL) were determined by an automatic colorimetric method (Hitachi; Boehringer Mannheim). LDL-cholesterol (LDL-c) was calculated using the Friedewald formula. All blood samples were obtained in a fasting state at 8 am.

Globally, the normal range of TSH level is not definitely set. Different regions, ages and ethnic groups may have different ranges. To set a reference range for normal TSH values, we selected 250 healthy participants aged 20–80 and carefully excluded those who self-reported thyroid disease or goiter, as well as those who had thyroid disease family history. We tested their TSH levels and set the range of 2.5th- 97.5th percentile as the reference range of normal TSH values. The resulting range was 0.34 mIU/L- 4.22 mIU/L. TSH level lower than 0.34 mIU/L was defined as hyperthyroidism (including subclinical hyperthyroidism). TSH level higher than 4.22 mIU/L was defined as hypothyroidism (including subclinical hypothyroidism).

Among the 5154 subjects included in the research survey, the overall prevalence of thyroid dysfunction was 6.72% (with 2.72 and 4% for hyper- and hypo-thyroidism, respectively, as shown in the result section in Table 1). The TPOAb positive rate was 10.7% (Table 1). The trend was consistent with a recent large-scale epidemiological survey in China [14]. In male, there was no significant difference between the prevalence of hyperthyroidism and hypothyroidism. In female, the incidence of hypothyroidism and TPOAb positive were significantly higher than that of hyperthyroidism (Table 1). With the increase of age, the incidence of hyperthyroidism and hypothyroidism both increased in male, which was consistent with the survey in other countries [15].

The effect of alcohol consumption on AITD is elusive. Some previous research found no association between alcohol consumption and Graves’ Disease [16], while others suggested that moderate alcohol consumption might reduce the risk of Graves’ disease [17]. Autoimmune thyroid disease seems to be much more dependent on environmental factors than hitherto anticipated. A population-based case-control study in Denmark likewise observed that moderate alcohol consumption reduced the risk of overt autoimmune hypothyroidism [18]. In our study, alcohol consumption was found to be associated with reduced risk in hyperthyroidism, hypothyroidism and positive TPOAb (see Result section, Tables 3 and 4). The observed associations were independent of the type of alcohol (e.g. wine or beer), or gender. A protective effect of alcohol had also been reported for other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes [19]. However, the mechanism of action of these protective effects of alcohol remains poorly understood.

The association between smoking and autoimmune thyroid disease (AITD) was explored by many epidemiological studies. It was confirmed that smoking is a risk factor for the development of Graves’ hyperthyroidism (GH), especially for Graves’ ophthalmopathy (GO) [20]. In consistence with these previous reports, our study also found smoking associated with increased incidence of hyperthyroidism. The association between smoking and hypothyroidism is less clear. According to a review by Vestergaard P. (2002), a number of previous studies failed to find any association between smoking and hypothyroidism [8]. However, several recent researches have provided strong evidence that smoking might reduce incidence of hypothyroidism [21, 22]. In our study, positive TPOAb was less prevalent in subjects who were smokers at the time of the study than it was in subjects who were not smoking (7.6% vs. 12.0%, P < 0.001). Similarly, hypothyroidism was less prevalent in smokers than it was in non-smokers (2.4% vs. 4.9%, P < 0.001). The mechanism of the protecting effect of smoking for hypothyroidism is unclear. Some research indicated that nicotine might play a role. Nicotine was thought to increase Tregs-mediated immune suppression of lymphocytes via α7 nicotinic acetylcholine receptor (α7 nAChR) [23]. Cigarettes smoking exposure was believed to inhibit Th1 cytokine production and may lead to enhancement of Th2 response [24]. Since Hashimoto’s thyroiditis was regarded as predominantly a disease caused by increased Th1 production, while Graves’s disease may be caused by the enhancement of Th2 response, the suppressive effect of cigarette smoking on Th1 response and the resulting enhancement of Th2 response may explain the decreased risk of hypothyroidism and increased risk of hyperthyroidism among smokers [25]. The effect of the smoking on the hyperthyroidism and hypothyroidism is interesting. Further research is required to better understand the underlying mechanisms.

Little has been done to examine potential impact of exercise and physical activities on thyroid function. Studies in healthy, well-trained male athletes had shown that short-term high intensity exercise increased levels of circulating thyroid hormones [26]. In contrast, for long-term exercise, a study of men after six months of endurance training reported that free T4 concentrations were slightly decreased, with no change in TSH [27]. In our study, we did not find any correlation between exercise and hyperthyroidism. However, in the case of hypothyroidism, the prevalence was lower in the subjects who exercised compared to those who did not (3, 8% vs. 5.5%). In the logistic regression analysis, exercise was found to be associated with risk reduction in hypothyroidism, although no association in any direction was found between exercise and positive TPOAb. These results indicate that regular physical activity may be a protective factor for hypothyroidism. In our research we also found that subjects on weight watch had lower BMI as expected (22.686 ± 3.037 vs. 22.961 ± 3.463, P = 0.014), and lower prevalence of positive TOPAb and hypothyroidism (Table 3). However, there was no correlation between hyperthyroidism and weight watching or BMI. Many studies had reported that obesity can cause autoimmune disorders and increased TOPAb level, thus increases prevalence of hypothyroidism [28]. Our results were consistent with those reported in previous research.

Globally, iodine supplementation has been the primary method to prevent mental retardation caused by iodine deficiency. However, in the recent few decades, there was a concern that excessive iodine exposure in some individuals may increase the incidence of autoimmune thyroiditis. Some began to question mandatory iodization of salt. In our research, we found no difference in the prevalence of hyperthyroidism, hypothyroidism or positive TPOAb among subjects’ groups with different amount of iodized salt consumption.

In this survey, we found an interesting relationship between subject’s daily staple amount and their probability of developing TPOAb positive. It seemed that increased daily staple was correlated with lower risk of TPOAb positive (see Results section, Tables 3 and 4). Though the trend was moderate. The OR was 0.956 with 95%CI of 0.918–0.995. It was unclear how daily staple affects thyroid disease development. However, several studies had indicated that starvation could cause hypothyroidism. It was shown that during long term energy withdrawal, thyroidal superoxide anion was able to lower the thyroid hormones thyroxine (T4) and triiodothyronine (T3) and cause a hypothyroid state in pigeons [29]. It was possible that decreased staple intake might raise TPOAb level, thus provoke the development of hypothyroidism.

It is well known that Stress was a provoking factor in the pathogenesis of Graves’s disease. Stress may also precipitate patients who are predisposed to autoimmune thyroid dysfunction [30]. However, the relationship between stress and hypothyroidism remains obscure. Two previous studies conducted by Pan [31] and Rossana [32], respectively, did not find association between life events and the development of thyroid dysfunction. Many life style factors can evoke stress. Previous researches had detected insomnia [33] and chronic daily headache [34] as chronic stressors that can result in health problems. In our study, we evaluated potential association of these two stress factors with thyroid dysfunction. We found hyperthyroidism was less prevalent in people who suffered from insomnia than it was in people free of insomnia, although the prevalence for hypothyroidism was similar between the two groups. This was surprising as stress is known to trigger Graves Disease. However, it was possible that different types and degrees of stress affect thyroid function differently and insomnia-induced stress might be very different from those studied in previous research. For chronic daily headache, we found no association between headache and hyperthyroidism. However, prevalence of hypothyroidism was reduced in people who suffer from chronic daily headache (5.7% vs. 3.2%). Again, the difference in the type and degree of stress investigated might explain the different observations in our study versus those of others.