At present, there are different research results on the relationship between obesity and thyroid disease. Obesity can cause insulin resistance and hyperinsulinemia, making the body inclined to the state of energy reserve . This may inhibit the synthesis and release of thyroid hormones, and studies have shown that insulin itself can also promote abnormal proliferation of thyroid tissue [15, 16]. In addition, the accumulation of fat in the body and the increase of free fatty acids in circulation may also lead to steatosis and infiltration of the thyroid gland, resulting in changes in thyroid morphology and function . By comparing the thyroxine levels of patients before and after bariatric surgery, several studies found that TSH levels decreased significantly after bariatric surgery, and lasted for a long time without taking L-T4, indicating that subclinical hypothyroidism tends to be improved spontaneously after weight loss [18–20]. Since many weight loss operations are performed by gastrectomy, obesity-mediated subclinical hypothyroidism is more likely to be affected by some intestinal hormones . For example, GLP-1 can improve the activity of deiodinase and promote the synthesis of thyroid hormone, while the secretion of this hormone increases after weight loss . In addition, leptin secreted by adipose tissue has also been shown to affect the regulation of the hypothalamic-pituitary-thyroid axis, thereby inhibiting thyroid hormone release and stimulating TSH secretion [23–25].
In this study, difference and correlation analysis showed that the risk of subclinical hypothyroidism and thyroid nodules in obese patients (BMI ≥ 25 kg/m2) was higher than that in non-obese patients. Other factors associated with obesity and metabolic syndrome, such as waist circumference and blood pressure, however, were only associated with thyroid nodules. Two studies from South Korea on the clinical characters of subclinical hypothyroidism and thyroid nodules also found similar results [26, 27], although the level of BMI is positively correlated with the level of TSH, and this correlation persists even the TSH level fluctuates slightly within the normal reference range, the presence or absence of metabolic syndrome does not affect the occurrence of subclinical hypothyroidism. It is suggested that metabolic status may have a more significant effect on the occurrence of thyroid nodules than subclinical hypothyroidism. To some extent, this proves that there is no direct correlation between insulin resistance and subclinical hypothyroidism. In addition, a study of women with polycystic ovary syndrome(PCOS) found that other metabolic conditions were associated with TSH levels only in obese PCOS women , suggesting that obesity may be a necessary condition for mediating the mechanism of hyperinsulinemia on thyroid gland. In contrast, the relationship between thyroid nodules and metabolic disorders such as impaired glucose tolerance, metabolic syndrome and insulin resistance has been confirmed in a number of observational studies [29–31]. In our study, the high correlation between thyroid nodules and these indexes also suggests that the effect of adverse metabolic status on thyroid may be more emphasis on non-functional and morphological changes, which does not need to be mediated by obesity. This needs to be proved by further pathological results.
Among participants in different age groups, we found that people aged 40–60 had the highest risk of subclinical hypothyroidism. But for thyroid nodules, the older the age, the greater the risk. In elderly patients, the effect of BMI on thyroid nodules is also more obvious. The different effects of age on the two diseases may be due to subtle differences in pathogenesis, the exact mechanism of which is still unclear. However, we speculate that the protective effect of advanced age (> 60 years old) on subclinical hypothyroidism may be due to the decrease of fat factors such as leptin in the elderly, which can inhibit the secretion of thyroid hormone. In contrast, the occurrence of thyroid nodules is less affected by the regulation of hormones in the body, while the slow local metabolism of the thyroid gland in the elderly leads to the accumulation and proliferation of thyroid tissue, which has a synergistic effect with obesity. In terms of gender, the prevalence of thyroid disease was higher in women than in men, but subgroup analysis did not show that BMI had different effects on men and women. Our findings may be due to a small sample size, but the association between gender, obesity and thyroid disease may be complex. A previous study, also from Tianjin, China, showed that BMI was not associated with the incidence of subclinical hypothyroidism in women, but played a protective role in men , which contradicted the results of many previous studies [33–35]. Estrogen may have a unique pathological effect on thyroid gland so that women are susceptible to thyroid disease , but it also has a different effect on the distribution and metabolism of human fat than that of men. These two mechanisms make the relationship between obesity and thyroid disease different in different genders, and more in-depth research is needed to prove it.
Thyroid autoantibody levels are increased in patients with subclinical hypothyroidism, but there is no such trend in patients with thyroid nodules. Patients with TPOAb have the highest risk of subclinical hypothyroidism because TPOAb has been shown to play a direct role in thyroid destruction through antibody and complement-mediated cytotoxicity. In the subgroup analysis, BMI was directly associated with the risk of subclinical hypothyroidism only in antibody positive patients. There is often abnormal lymphocyte infiltration in the thyroid tissue of these patients, and studies have shown that obesity itself is also a chronic inflammatory state. In obese patients, there is an increasing trend of cytokines secreted by immune cells as inflammatory markers . By comparing the changes of inflammatory factors in patients with subclinical hypothyroidism after weight loss, Zhu, C et al found that the decreasing trend of pro-inflammatory factors such as IL-6, CRP and TNF- α was positively correlated with the decrease of TSH . This suggests that obesity and Hashimoto's thyroiditis may have a synergistic effect on thyroid tissue damage, making the effect of obesity on thyroid more obvious. Hashimoto's thyroiditis patients with obesity are more likely to develop subclinical or even clinical hypothyroidism than non-obese patients.
Current studies have shown that lifestyles such as smoking and drinking have certain benefits for thyroid disease, but the exact mechanism is unknown. A cohort study of 10 million people in South Korea showed that smokers and drinkers had a reduced risk of thyroid cancer, and the two had a synergistic effect . Other studies have shown that stopping smoking leads to an increased risk of thyroid autoantibodies, which leads to subclinical hypothyroidism . In our study, the effects of smoking and drinking on thyroid disease showed very complex results after multivariate analysis and subgroup analysis. Univariate logistics regression showed that smoking had a certain protective effect on two kinds of thyroid diseases, and the prevalence rate of two kinds of thyroid diseases in smokers was significantly lower than that in non-smokers. However, after adjusting other covariates, the protective effect of smoking was eliminated. In the subgroup analysis, no association between smoking and disease was observed in a subgroup. The history of alcohol addiction only has a protective effect on thyroid nodules, especially in smokers and non-obese people, drinking has a significant statistical significance on the reduction of the prevalence of thyroid nodules.
It is worth noting that in the subgroup analysis, smokers were more likely to be affected by BMI-induced subclinical hypothyroidism than non-smokers after matching other factors. Similarly, drinkers are more susceptible to the effects of BMI on thyroid nodules than non-drinkers. This may be due to our small sample size, because there are only 38 patients in the subgroup of smoking with subclinical hypothyroidism and 36 patients with thyroid nodules while drinking alcohol. Considering that the lifestyle of smoking and drinking can also lead to obesity and metabolic disorders, the proportion of obese patients is relatively large. Previous studies have also shown that there is no difference in the effects of obese subclinical hypothyroidism between smokers and non-smokers . However, the independent protective effect of smoking and drinking on thyroid disease seems to contradict the harm caused by obesity, especially the protection of drinking on thyroid nodules may interact with the pathological mechanism of obesity on thyroid disease. Therefore, the future research on the risk of thyroid disease should pay more attention to the people who are obese at the same time of smoking and drinking.
In our study, urinary iodine levels were used as continuous variables and enumerative variables, respectively, but no differences were found between patients with subclinical hypothyroidism and thyroid nodules and non-patients. This shows that iodine nutrition status has no effect on the prevalence of thyroid diseases, and the results are not consistent with the results of the national iodine nutrition survey in China . Although it is considered that the effect of iodine on thyroid is long-term, the cross-sectional difference of small sample size may not be significant. However, it also shows that high iodine diet as a lifestyle has less significant effect on thyroid than obesity, smoking and drinking, and there is no need to deliberately control iodine intake for prevention of subclinical hypothyroidism and thyroid nodules.
Our study has the following limitations. Because it is based on population screening, the sample size of the disease is small. In addition, the study is a cross-sectional study, so it is not possible to determine the causal relationship between risk factors and disease. For the subgroups in this study, larger studies are still needed to confirm the exact relationship between the covariates.