INTRODUCTION
Sleep is an important component of health status. Although many people recognize that sleep is essential for life, they do not complete the required sleep duration due to social, leisure, or business-related activi-ties [1]. If the situation persists, it can negatively affect lifestyle and men-tal status and can lead to the occurrence of several diseases. In particular, insufficient sleep aggravates depression, physical health, immune, car-diovascular, and metabolic syndrome [2]. It affects patients with chronic pain and physical and psychological symptoms [3]. Sleep is related to an increased risk of mortality [4] and affects metabolic syndrome by sex [5]. Increased risk of all-cause mortality such as ischemic heart disease, other heart disease, cerebrovascular accidents, cancer, suicide and homicide were associated with short and long sleep duration [4]. Concerning met-abolic syndrome, men are associated with short sleep duration, and women are affected by long sleep duration [5]. Therefore, it is essential to sleep properly to maintain adequate sleep duration and prevent diseases.
There are many thyroid diseases such as autoimmune disease and Graves’ disease, which cause hyperthyroidism and Hashimoto's thyroid-itis, which results in hypothyroidism [6]. Based on the reference range of serum thyroid stimulating hormone (TSH) (0.62-6.68 mIU/L), the prev-alence of subclinical hypothyroidism and subclinical hyperthyroidism was 0.73% (0.40% men, 1.10% women) and 3.10% (2.26% men, 4.04% women), respectively, in Korea, from 2013-2015 [7]. Previous studies have investigated the association between sleep and thyroid diseases [8]. Sleep can affect hormone secretion, thyroid dysfunction, subclinical hyperthy-roidism, and subclinical hypothyroidism [8]. Insufficient sleep indicated a significantly increased risk of subclinical hyperthyroidism not hypo-thyroidism; however, prolonged sleep were elevated risk of subclinical hyperthyroidism and hypothyroidism [8]. A previous study indicated an increase in serum concentrations of fT3 and fT4 among individuals with sleep restriction compared to normal sleepers [9]. Furthermore, acute partial sleep deprivation has been shown to be influenced by en-docrine homeostasis, health, and wellbeing status [9].
Although numerous studies have shown the associations between sleep duration and thyroid hormones, little is known about whether sleep durations were associated with thyroid disease. Further, few studies have investigated the association between sleep duration and the preva-lence of thyroid disease according to sex. Thus, our study examined sleep duration and thyroid disease according to sex among South Kore-an adults, using data from the Korea National Health and Nutrition Ex-amination Survey (KNHANES) from 2016 to 2018.
METHODS
Study population and database information
The KNHANES is a national questionnaire designed to analyze the health and nutrition stations among Koreans and is often used as pri-mary data. The questionnaire provides objective and standardized sources while estimating the prevalence of diseases, conditions, and risk behaviors [10]. The study data were extracted from the seventh KNHANES, conducted from 2016-2018. First, 24,269 participants were identified from the KNHANES VII-3. We excluded the data collected from participants who were <19 years (n=4,880), cases with missing in-formation concerning the average sleep time per day during the weekday (n=1,116) and weekend (n=1), as well as cases involving no responses concerning average sleep time per day during the weekday (n=711) and the weekend (n=6). After excluding the data, 17,555 individuals (7,641 men, 9,914 women) were included in this study.
Definition of thyroid disease
Thyroid disease includes autoimmune disease, Graves’ disease, Hashi-moto's thyroiditis, hyperthyroidism, and hypothyroidism [6]. In this study, participants were classified as having thyroid diseases and not having thyroid disease. Thyroid disease was defined as participants who responded “ yes” to the following questions from the KNHANES: 1) Have you been diagnosed with thyroid disease by a physician? 2) Are you currently suffering from thyroid disease? Following these questions, individuals were defined as having thyroid disease diagnosed by a physi-cian and currently suffering from thyroid disease. Participants without thyroid disease were defined as individuals who answered “ no” to the above-mentioned questions.
Assessment of sleep duration
Sleep duration was assessed by the following questions: (1) On the week-day, what time did you go to sleep and wake up? (2) On the weekend, what time did you go to sleep and wake up? Using these questions, we calcu-lated the average sleep duration on weekdays and weekends. We classi-fied individuals into three groups according to previous research [11]: in-sufficient sleepers (<7 hour/day), normal sleepers (7-8 hour/day), and prolonged sleepers (≥9 hour/day).
Covariates
The following covariates were obtained using a standardized question-naire in the KNHANES: sex, age, household income, education, marital status, current smoking, high-risk alcohol consumption, body mass in-dex, working hours, physical activity, and year. The participants were stratified by age into five groups: 19-29 years, 30-39 years, 40-49 years, 50-59 years, and ≥60 years of age. The participants were stratified by household income into four categories: low, low-moderate, moderate-high, high. The individuals were divided by education into four groups: ele-mentary school, middle school, high school, and college and above. Cur-rent smoking was defined as participants who smoked >100 cigarettes in their lifetime and current smokers [12]. High-risk alcohol consumption was defined as the consumption of more than 14 drinks per week for men and 10 drinks per week for women [11]. Body mass index (BMI) was stratified into three groups: underweight (BMI<18.5 kg/m2), normal (18.5 kg/m2 ≤BMI<25 kg/m2), and obese (BMI≥25 kg/m2) [13]. Working hours per week were classified into five groups: not working, <20, 20-39, 40-59, and ≥60 [14]. Physical activity was defined as moderate-in-tensity physical activity for more than 150 minutes per week, high level of physical activity for more than 75 minutes, or a mix of moderate-and high-intensity physical activity [15].
Statistical analysis
We assessed the association between sleep duration and the prevalence of thyroid disease according to sex. A chi-squared test was performed to assess baseline characteristics. Multiple logistic regression analyses were performed to calculate odds ratio (OR) and 95% confidence interval (CI) for general characteristic and thyroid disease. Sleep duration and thyroid disease according to sex were used for multiple logistic regression analy-ses. Statistical significance was set at p <0.05. SAS 9.4 (SAS Institute Inc., Cary, NC, USA) was used for all statistical analyses.
RESULTS
The general characteristics of the study population are summarized in Table 1. The study included 7,641 men and 9,914 women. There were 685 and 16,870 patients with and without thyroid disease, respectively. The prevalence of thyroid disease was 1.4% and 5.8% in men and women, re-spectively. Approximately, 4.1%, 3.8%, and 3.8% of the cases involving in-sufficient sleep, normal sleep, and prolonged sleep were associated with the prevalence of thyroid disease. Statistical significance was observed for sex, age, marital status, current smoking, and working hours among participants with thyroid disease (p-value <0.0001, respectively).
Table 1.
General characteristics of study population in the Korea National Health and Nutrition Examination Surveys 2016-2018
Table 2 shows that the association between general characteristic and thyroid disease among South Korean adults. Women were statistically significant for thyroid disease (OR=4.52, 95% CI=3.56-5.73). However, the prevalence of thyroid disease was not associated with sleep duration.
Table 2.
The association between general characteristic and prevalence of thyroid disease among Korean adults in the Korean National Health and Nutrition Examination Surveys 2016-2018
In the subgroup analysis, We compared sex differences in the association between sleep duration and the prevalence of thyroid disease among South Korean adults (Figure 1). Among men, insufficient sleep (OR=1.85, 95% CI=1.19-2.87) and prolonged sleep (OR=1.71, 95% CI=1.02-2.87) were associated with the prevalence of thyroid disease; however, the same was not observed for women.
Figure 1.
The sex difference in the association between sleep duration and prevalence of thyroid disease among South Korean adults. Results are demonstrated odds ratios and 95% confidence intervals. Adjusted for age, household income, education, marital status, current smoking, high-risk alcohol consumption, body mass index, working hours, physical activity, and sleep duration.
DISCUSSION
The results of the present study demonstrated that sleep duration was not associated with the prevalence of thyroid disease. However, we found that there was a sex difference between sleep duration and the preva-lence of thyroid disease. In subgroup analysis, insufficient and prolonged sleep was related to the risk of thyroid disease for men. However, no sta-tistically significant association was observed in women.
Most previous studies have confirmed the effects of sleep on various diseases and mortality, including cardiometabolic health [1], depression [16], chronic pain [3], increased risk of death [17], myriad adverse behav-ioral consequences [2] and metabolic syndrome [5]. Based on those studies, our study defined 7-8 hours as adequate sleep duration which was found to be preventive factor for thyroid disease. However, few studies have investigated the influence of sleep on thyroid function by sex, and there is a lack of information concerning the topic.
In previous studies, subclinical thyroid disease was associated with short and long sleep durations [8]. Based on this study, short sleep was increased in hyperthyroidism; however, the same was not observed in hypothyroidism. Further, short sleep was associated with a high proba-bility of TSH suppression. Long sleep duration was associated with in-creased TSH secretion and subclinical hypothyroidism. In addition, both short sleep and long sleep are increased in hyperthyroidism [8].
Although there are few studies detailing sleep duration and thyroid disease, several studies have shown that changes in serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were controlled by circadian rhythm and partial sleep and they impacted secretory activity and thyroid function [9,18–20]. Several studies have evaluated the influence of sleep on TSH, fT3, and fT4, which are affected by thyroid and other diseases [9]. In previous studies, women were higher 24 h-fT4 concentrations than men. In both men and women, partial sleep loss was related to a decline in free T4 and TSH; however, the results indicated that women had a statistically signif-icant association [20]. Ferdinand [19] showed that elderly men had lower average nocturnal TSH levels compared to young individuals. In these sleep loss studies, sleep restriction for two consecutive nights among young men influenced the thyrotrophic axis [9]. Serum concentrations of fT3 and fT4 were increased, and serum TSH levels were slightly ele-vated in the evening hours [9]. Additionally, studies of thyrotropin secretion profiles demonstrated that TSH concentrations were slightly higher in men than in women at night [18].
According to our results, sleep duration was not associated with the prevalence of thyroid disease compared to a previous study [8]. A previous study explained that sleep duration exerted an influence on subclinical hyperthyroidism and subclinical hypothyroidism with thyroid hormone [8]. Further, our study indicated a statistical significance for men, when the correlation between insufficient sleep and prevalence of thyroid dis-ease was analyzed by sex. Our study data from KNHANES 2016-2018 were not investigated for serum concentrations of TSH, fT3, and fT4. We could not confirm the mechanism underlying the association between sleep duration and the prevalence of thyroid disease. Therefore, our study is based on several previous studies. Thus, more studies are required to examine the influence of sleep duration on thyroid disease by sex, sleep quality, large population, and nationally representative data.
This study had several strengths. First, this study used a nationally representative sample with a large population compared to previous studies. To our knowledge, this is the first study detailing sex difference between sleep duration and the prevalence of thyroid disease. Second, various covariables were used in our studies and defined as thyroid dis-ease with physician diagnosis and current prevalence to ensure precise measurement. Third, we investigated the wakeup time and bedtime on weekdays and weekends, respectively, using KNHANES questionnaires. Using these individuals'sleep time, we calculated the average sleep duration on weekdays and weekends.
However, there are some limitations to our study. First, sleep quality was not analyzed in the present study. The sleep quality and sleep duration affected thyroid disease [21–24], so it should be included in future studies. Second, there was no information about TSH, fT4, and fT3 in the KNHANES from 2016 to 2018. Therefore, thyroid hormones could not be measured. However, we could provide exact measurements as we used the KNHANES questionnaires for information concerning physi-cian diagnosis and the prevalence of thyroid disease. Third, hyperthy-roidism, hypothyroidism, thyroid positive nodules and Hashimoto thy-roiditis were included thyroid disease in KNHANES. This study was not investigated in detail, such as the relationship between hyperthyroidism and sleep duration.
CONCLUSIONS
In conclusion, sex differences showed a relationship between sleep du-ration and thyroid disease. We propose to add thyroid hormones in gen-eral health examination blood tests and include thyroid cancer in the national cancer examination for examination once every two years for men and women. Additional studies are needed to confirm the association of sleep duration and thyroid disease with sleep quality according to sex and analyses with other interesting variables.
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