How was a sedentary lifestyle associated with the prevalence of thyroid nodules among government staff?

doi:10.21203/rs.3.rs-2413159/v1

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Research Article

How was a sedentary lifestyle associated with the prevalence of thyroid nodules among government staff?

https://doi.org/10.21203/rs.3.rs-2413159/v1

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Purpose

A sedentary lifestyle has been an increasing public health issue especially since the outbreak of COVID-19. Limited evidence was reported on the association between sedentary lifestyle and prevalence of thyroid nodules, a benign but prevalent health concern in the modern society.

Methods

This study used the annual examination data of Guangzhou public officials in 2020. Thyroid nodules were diagnosed following standard criteria. Sedentary lifestyle was self-reported as spending < 2 h, 2 ~ 4 h, 4 ~ 6 h, or > 6 h per day staying sedentary. Multivariate logistic regressions were used to evaluate the association between sedentary lifestyle and thyroid nodules. Results were also stratified by covariates.

Results

Among 18,023 participants, sedentary lifestyle was positively associated with the prevalence of thyroid nodules, with ORs (95%CIs) of 1.23 (1.05–1.43), 1.69 (1.45–1.96), and 1.74 (1.49–2.03) for those with daily sedentary time of 2 ~ 4h, 4 ~ 6h, >6h compared with < 2h group (P-trend < 0.01). The three estimates (i.e., 1.29, 1.92, and 1.96 respectively) were stronger among the participants with thyroid nodules of TI-RADS-2 stage compared with other groups. Stratified analysis also indicated a modification effect of age, with the estimates for participants aged ≥ 50 being 1.21, 1.79 and 2.00, compared with 1.04, 1.29 and 1.31 among those aged 35 ~ 49, and 1.13, 1.37 and 1.34 among those under 34 years old (P-interaction = 0.012).

Conclusions

A sedentary lifestyle may be associated with increased prevalence of thyroid nodules among government staff, with the elderly being the most vulnerable. The sedentary lifestyle should be modified to promote their well-being.

Thyroid nodules

sedentary lifestyle

government staff

risk factor

population health

A sedentary lifestyle has become a common health problem in modern society. Almost one-third of the world's population are physically inactive[1], and the rate is particularly higher among the Chinese. A study in 2019 estimated that 43% of Chinese office workers sit for at least 8 hours per day[2]. It has become more common an issue since the outbreak of the COVID-19 pandemic when more people have to work remotely for certain reasons[3]. It has been well documented that a sedentary lifestyle is an independent predictor for multiple metabolic disorders including insulin resistance[4, 5], even among those who had sufficient time of physical activities after work[6, 7]. In addition, various cancers were found to be related to a sedentary lifestyle, including endocrine system cancers (e.g., ovarian[8], breast[9], endometrial[10], prostate cancer[11]) as well as the common ones (e.g., colorectal[12], lung cancer[10]). Therefore, changing a sedentary lifestyle may be an important and effective approach to improve the population health.

Thyroid nodules (TNs) are one of the most common disorders of the endocrine system[13]. The prevalence of TNs is estimated to be as high as 36.9% in China in 2017[14]. Among these people, about 7–15% may end up with thyroid cancer[15]. Most TNs are initially asymptomatic, thus, are difficult to be detected until later stages. In addition, people diagnosed with TNs usually need to take an annual examination to prevent exacerbation, resulting in psychological stress and financial loss of the patients[15].

Emerging evidence shows that the risk of TNs may be partially attributed to a sedentary lifestyle and the association was biologically plausible. Sunshine exposure usually is limited among the sedentary people, leading to a deficiency of serum vitamin D. However, vitamin D is directly protective against TNs[16]. Besides, vitamin D deficiency was considered to be associated with an increased level of serum thyroid stimulating hormone (TSH) which was responsible for TNs and thyroid carcinoma[17] [18]. Other pathways such as chronic low-level inflammation, insulin resistance and metabolic disorders may also interpret the association between a sedentary lifestyle and the risk of TNs, according to the existing clues [18] [19–23] [5]. However, limited epidemiological evidence was available on the potential impact of a sedentary lifestyle on the prevalence of TNs.

To address this important research gap, we investigated the association between the prevalence of TNs and the duration of daily average time of being sedentary. We also evaluated the potential modification effect of multiple individual factors by stratified analysis.

Study population

We focused on the participants who visited the Guangzhou Cadre Health Management Center during 2020. The center is responsible for annual examinations of all government staff in Guangzhou. We included the participants who 1) voluntarily completed the questionnaire and signed informed consent; 2) had completed thyroid ultrasound results and other required information. The participants 1) with clinically diagnosed mental illness; 2) with cancers; or 3) being pregnant were excluded. Finally, 18,023 individuals, aged 21–85 years, were included in this study. This work was approved by the Ethics Committee of the Guangzhou Cadre Health Management Center.

Outcome Assessment

Color Doppler ultrasonography was performed by experienced physician for each participant, with TNs being diagnosed following the "Expert consensus on some common clinical problems in ultrasound of thyroid and related cervical lymph nodes (2018 version)"[24]. Specifically, we defined our primary outcome, the TNs, according to the TI-RADS criteria (i.e., TI-RADS1: no nodules; TI-RADS2: benign; TI-RADS3: mildly suspicious; TI-RADS4: moderately suspicious; TI-RADS5: highly suspicious). Secondary outcomes included multiple metrics of TN features measured with ultrasound test, including blood flow signal, aspect ratio, unclear margins, calcification, anechoic, mixed echogenicity, isoechoic, hypoechoic and hyperechoic nodules.

Clinical Diagnosis And Examination

General information was collected for each participant, including height, weight, blood pressure, chronic diseases and medications. Venous blood for biochemical tests was collected in the morning, with all participants being fasted for at least 8 hours. The blood biochemical biomarkers included blood glucose, lipids, liver function biomarkers, kidney function biomarkers, etc. The existing condition of diabetes, hyperuricemia, hypertension and dyslipidemia were all diagnosed by physicians following the standard criteria listed in the supplement (Table S1).

Study Questionnaire

The questionnaire was filled out by the study participants under the advice of trained medical professionals. According to the length of sedentary time during the day, participants were classified into four groups (i.e., < 2 hours, 2–4 hours, 4–6 hours and > 6 hours group). The potential confounders included gender, age, overweight (i.e., BMI ≥ 24 according to Chinese adult criteria[25]), physical activity (i.e., 1: Never; 2: Sometimes; 3: Regular: averagely ≥ 3 times per week and > 30 minutes per time), sleep time (i.e., < 5, 5–7 (including 7), 7–9, > 9 hours), smoking (i.e., more than 1 cigarette per day for ≥ 1 year), alcohol drinking (i.e., more than once a week for ≥ 1 year), perception of stress (i.e., no, a little, significant, extreme) and medication use (regularly taking drugs including antihypertensive drugs, hypoglycemic drugs, lipid-lowering drugs, uric acid-lowering drugs, anti-arrhythmic drugs, asthma relief drugs, cardiovascular drugs, glucocorticoids, painkillers, tranquilizers, antidepressants, birth control pills).

Statistical analysis

All the variables in this study was categorical and described using number and percentage, with the difference between people with and without TNs being examined using χ2 tests. The associations between sedentary lifestyle and thyroid nodules were explored using logistic regression, where variables with a P < 0.1 in the chi-square test were sequentially included as covariates in the adjusted models. The details were described as following:

The crude model only included a single variable of sedentary lifestyle (i.e., < 2 hours, 2–4 hours, 4–6 hours and > 6 hours group).

Adjusted model 1 adjusted for age and gender.

Adjusted model 2 additionally adjusted for overweight and physical activity.

Adjusted model 3 additionally adjusted for sleep time, smoking and alcohol consumption.

Adjusted model 4 additionally adjusted for dyslipidemia, hyperuricemia and perception of stress, which is the final model for this study.

Results were further stratified by the abovementioned covariates and nodules with different features. The significance of modification effects was tested by adding an interaction term into the model. To confirm the robustness of our findings, we conducted a sensitivity analysis by excluding population with medication use and reran the models. Two-sided P < 0.05 was considered statistically significant. We used “forestplot” and “ggplot2” for result visualization.

Characteristics of the study population

Characteristics of the study population are shown in Table 1. Among the 18,023 participants, 35.03% were females, 46.64% aged 35–49 and 32.58% aged ≥ 50. Most individuals had > 6 h sedentary time per day (35.88%), followed by the 4–6 h group (35.49%), and the < 2 h group (6.02%). 6,216 (34.5%) participants were diagnosed with TNs. χ² test results showed that the distribution of TNs patients differed across different levels of sedentary lifestyle (P < 0.001). For covariates, TNs patients were more likely to be female, older, smoking less, drinking more alcohol, dyslipidemia, not overweight, hyperuricemia, sleep less, more stressed, and less physically active (P < 0.1). Therefore, these variables were included as covariates in the adjusted models.

Table 1

Characteristics of the study population
Factors	Total (n = 18,023)	TNs (n = 6,216)	No-TNs (n = 11,807)	P-value^⁎
Sedentary lifestyle
< 2 h	1085 (6.02)	301 (4.84)	784 (6.64)	< 0.001
2 ~ 4 h	4076 (22.62)	1238 (19.92)	2838 (24.04)
4 ~ 6 h	6396 (35.49)	2308 (37.13)	4088 (34.62)
> 6 h	6466 (35.88)	2369 (38.11)	4097 (34.70)
Gender
Male	11709 (64.97)	3269 (52.59)	8440 (71.48)	< 0.001
Female	6314 (35.03)	2947 (47.41)	3367 (28.52)
Age
≤ 34	3746 (20.78)	921 (14.82)	2825 (23.93)	< 0.001
35 ~ 49	8406 (46.64)	3032 (48.78)	5374 (45.52)
≥ 50	5871 (32.58)	2263 (36.41)	3608 (30.56)
Smoking
No	13782 (76.47)	4940 (79.47)	8842 (74.89)	< 0.001
Yes	4241 (23.53)	1276 (20.53)	2965 (25.11)
Alcohol consumption
No	10924 (60.61)	3460 (55.66)	7464 (63.22)	< 0.001
Yes	7099 (39.39)	2756 (44.34)	4343 (36.78)
Hypertension
No	14475 (80.31)	5025 (80.84)	9450 (80.04)	0.225
Yes	3548 (19.69)	1191 (19.16)	2357 (19.96)
Dyslipidemia
No	8247 (45.76)	2727 (43.87)	5520 (46.75)	< 0.001
Yes	9776 (54.24)	3489 (56.13)	6287 (53.25)
Overweight
No	9652 (53.55)	3492 (56.18)	6160 (52.17)	< 0.001
Yes	8371 (46.45)	2724 (43.82)	5647 (47.83)
Hyperuricemia
No	10423 (57.83)	3724 (59.91)	6699 (56.74)	< 0.001
Yes	7600 (42.17)	2492 (40.09)	5108 (43.26)
Diabetes
No	16689 (92.60)	5764 (92.73)	10925 (92.53)	0.654
Yes	1334 (7.40)	452 (7.27)	882 (7.47)
Sleeping time
< 5 h	1130 (6.27)	392 (6.31)	738 (6.25)	0.057
5 ~ 7 h	11639 (64.58)	4083 (65.69)	7556 (64.00)
> 7 h	5254 (29.15)	1741 (28.01)	3513 (29.75)
Perception of stress
No	2379 (13.20)	695 (11.18)	1684 (14.26)	< 0.001
A little	10368 (57.53)	3627 (58.35)	6741 (57.09)
Significant	4299 (23.85)	1550 (24.94)	2749 (23.28)
Extreme	977 (5.42)	344 (5.53)	633 (5.36)
Physical activity
Never	986 (5.47)	396 (6.37)	590 (5.00)	< 0.001
Sometimes	9977 (55.36)	3443 (55.39)	6534 (55.34)
Regular	7060 (39.17)	2377 (38.24)	4683 (39.66)
Medication use
No	14608 (81.05)	5004 (80.50)	9604 (81.34)	0.195
Yes	3415 (18.95)	1212 (19.50)	2203 (18.66)
Values were presented with n (%). TNs: thyroid nodules.
^⁎P-value between TNs and control group were tested by χ² test.

Positive associations between sedentary lifestyle and TNs

The results of the crude and the main adjusted models were shown in Table 2. The results for other models in the sequential analysis were shown in Figure S1. According to the estimates in Table 2, the increase in daily sedentary time was positively associated with the prevalence of TNs, with ORs of 1.23 (1.05–1.43), 1.69 (1.45–1.96) and 1.74 (1.49–2.03) for 2 ~ 4 h, 4 ~ 6 h and > 6 h respectively compared with individuals with daily sedentary time < 2 h (P-trend < 0.001). When the results were stratified by TNs stages (i.e., TI-RADS2, TI-RADS3 and TI-RADS ≥ 4), we found that the ORs and P-trends across groups of different sedentary time remained significant. Generally, the TI-RADS2 group had the highest ORs in both crude (1.33–2.29) and main adjusted models (1.29–1.96), except for the group with daily sedentary time > 6 h. Table S2 shows that the association remained consistent after excluding participants with medication use.

Table 2

Associations between sedentary lifestyle and the prevalence of TNs as well as the associations across groups with different TN stages
Outcome	Daily sedentary time	Number of Cases: Controls*	Crude model		Main adjusted model
Outcome	Daily sedentary time	Number of Cases: Controls*	OR (95% CI)	P-trend	OR (95%CI)	P-trend
TNs	< 2 h	301: 784	1.00 (ref)		1.00 (ref)
	2 ~ 4 h	1238: 2838	1.14 (0.98–1.32)		1.23 (1.05–1.43)
	4 ~ 6 h	2308: 4088	1.47 (1.28–1.70)		1.69 (1.45–1.96)
	> 6 h	2369: 4097	1.51 (1.31–1.74)	< 0.001	1.74 (1.49–2.03)	< 0.001
TI-RADS2	< 2 h	73: 784	1.00 (ref)		1.00 (ref)
	2 ~ 4 h	352: 2838	1.33 (1.02–1.73)		1.29 (0.99–1.69)
	4 ~ 6 h	796: 4088	2.09 (1.63–2.69)		1.92 (1.48–2.50)
	> 6 h	874: 4097	2.29 (1.78–2.94)	< 0.001	1.96 (1.51–2.56)	< 0.001
TI-RADS3	< 2 h	211: 784	1.00 (ref)		1.00 (ref)
	2 ~ 4 h	823: 2838	1.08 (0.91–1.28)		1.23 (1.03–1.47)
	4 ~ 6 h	1403: 4088	1.28 (1.08–1.50)		1.63 (1.37–1.95)
	> 6 h	1370: 4097	1.24 (1.05–1.46)	< 0.001	1.67 (1.40–2.00)	< 0.001
TI-RADS ≥ 4	< 2 h	12: 784	1.00 (ref)		1.00 (ref)
	2 ~ 4 h	45: 2838	1.04 (0.55–1.97)		1.13 (0.59–2.16)
	4 ~ 6 h	75: 4088	1.20 (0.65–2.22)		1.43 (0.76–2.69)
	> 6 h	99: 4097	1.58 (0.86–2.89)	0.011	2.00 (1.06–3.79)	0.001

Stratified analysis and modification effects of covariates

In stratified analysis, a positive association was found in all groups, although a few were not significant. Population aged over 50 years were observed with the highest association between sedentary lifestyle and TNs, with ORs (95%CIs) of 1.21 (1.01–1.46), 1.79 (1.48–2.15), and 2.00 (1.62–2.46) for the 2 ~ 4, 4 ~ 6 and > 6 h sedentary group compared with the < 2 h group. In contrast, people aged 35 ~ 49 years had a relatively lower ORs of 1.04 (0.76–1.42), 1.29 (0.95–1.74), and 1.31 (0.97–1.78) respectively, while the estimates were 1.13 (0.59–2.14), 1.37 (0.74–2.54), and 1.34 (0.72–2.49 for those aged ≤ 34. The modification effect was significant (P-interaction = 0.012) for age but not for other covariates.

Association between sedentary lifestyle and different features of TNs

Table 3 shows the association of sedentary lifestyle with features of TNs. In general, the prevalence of TNs with a certain characteristic (relative to other TN patients or those without TNs) was associated with the increase of sedentary time. Given the small sample size, we did not find significant results for calcification, isoechoic and hyperechoic TNs groups whereas the results for TNs with aspect ratio was borderline significant. When comparing the results across participants with different TN characteristics, we found that those who had TNs without blood flow signal tended to be more vulnerable to the impact of increased sedentary time. The association did not significantly differ across other groups of TN characteristics.

Table 3

Association between sedentary lifestyle and different features of TNs
Features of TNs	Sedentary lifestyle		With character vs control group		Without character vs control group		With character vs without character
Features of TNs	Sedentary lifestyle		OR (95% CI)	P-trend	OR (95% CI)	P-trend	OR (95% CI)	P-trend
Blood flow signal		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 1,046)		2 ~ 4 h	1.38 (0.98–1.93)		1.35 (1.09–1.68)		0.98 (0.68–1.42)
		4 ~ 6 h	1.68 (1.20–2.34)		1.84 (1.50–2.27)		0.89 (0.62–1.27)
		> 6 h	1.54 (1.10–2.17)	0.035	1.88 (1.52–2.32)	< 0.001	0.79 (0.55–1.14)	0.028
Aspect Ratio > 1		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 141)		2 ~ 4 h	1.64 (0.56–4.79)		1.34 (1.10–1.63)		1.18 (0.40–3.48)
		4 ~ 6 h	2.34 (0.83–6.64)		1.78 (1.47–2.15)		1.29 (0.45–3.68)
		> 6 h	2.36 (0.82–6.77)	0.067	1.77 (1.46–2.15)	< 0.001	1.28 (0.44–3.67)	0.677
Unclear margins		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 237)		2 ~ 4 h	1.18 (0.62–2.24)		1.36 (1.11–1.66)		0.82 (0.43–1.57)
		4 ~ 6 h	1.56 (0.84–2.91)		1.80 (1.49–2.19)		0.83 (0.44–1.56)
		> 6 h	1.82 (0.96–3.44)	0.014	1.79 (1.47–2.18)	< 0.001	0.94 (0.50–1.77)	0.689
Calcification		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 75)		2 ~ 4 h	1.14 (0.32–4.07)		1.35 (1.11–1.64)		0.79 (0.22–2.83)
		4 ~ 6 h	1.53 (0.45–5.20)		1.79 (1.48–2.16)		0.79 (0.23–2.69)
		> 6 h	1.42 (0.41–4.95)	0.499	1.79 (1.47–2.17)	< 0.001	0.75 (0.22–2.62)	0.747
Anechoic		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 866)		2 ~ 4 h	1.48 (0.94–2.32)		1.34 (1.09–1.64)		1.12 (0.70–1.80)
		4 ~ 6 h	1.89 (1.22–2.93)		1.78 (1.46–2.18)		1.07 (0.68–1.69)
		> 6 h	1.93 (1.24–3.01)	0.001	1.78 (1.45–2.17)	< 0.001	1.12 (0.71–1.78)	0.747
Mixed echogenicity		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 361)		2 ~ 4 h	1.86 (1.01–3.40)		1.31 (1.07–1.60)		1.37 (0.74–2.55)
		4 ~ 6 h	2.04 (1.12–3.71)		1.77 (1.46–2.15)		1.13 (0.62–2.07)
		> 6 h	2.25 (1.23–4.14)	0.019	1.75 (1.44–2.13)	< 0.001	1.23 (0.67–2.28)	0.947
Isoechoic		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 214)		2 ~ 4 h	1.80 (0.87–3.72)		1.33 (1.09–1.61)		1.34 (0.64–2.79)
		4 ~ 6 h	1.67 (0.81–3.46)		1.79 (1.48–2.17)		0.92 (0.45–1.92)
		> 6 h	1.72 (0.82–3.60)	0.505	1.79 (1.47–2.18)	< 0.001	0.95 (0.45–1.99)	0.212
Hypoechoic		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 3,492)		2 ~ 4 h	1.27 (1.02–1.58)		1.59 (1.15–2.20)		0.79 (0.55–1.13)
		4 ~ 6 h	1.78 (1.44–2.20)		1.86 (1.35–2.56)		0.95 (0.67–1.34)
		> 6 h	1.75 (1.41–2.17)	< 0.001	1.95 (1.41–2.69)	< 0.001	0.88 (0.62–1.25)	0.765
Hyperechoic		< 2 h	1.00 (ref)		1.00 (ref)		1.00 (ref)
(n = 50)		2 ~ 4 h	0.97 (0.26–3.64)		1.35 (1.11–1.64)		0.72 (0.19–2.71)
		4 ~ 6 h	1.00 (0.27–3.66)		1.80 (1.49–2.17)		0.58 (0.16–2.12)
		> 6 h	1.21 (0.32–4.50)	0.608	1.79 (1.48–2.17)	< 0.001	0.68 (0.19–2.49)	0.726

In this study, each level increase in the daily sedentary time (i.e., 2h) was related to 23–46% increase in the prevalence of TNs, with the association being particularly stronger for the risk of TI-RADS2 TNs (29–46%). The ORs among the elderly doubled the estimates among the younger ones.

Association between sedentary lifestyle and TNs

We found a positive association between a sedentary lifestyle and the prevalence of TNs. Although no relevant studies were available for comparison, some existing evidence may support our findings. A cohort study of patients with TNs suggested that mental workers were more likely to suffer from TNs of increased sizes compared with manual workers (RR: 1.948, 1.638–2.164)[26]. A sedentary lifestyle may interpret the increased risk among the mental workers. Furthermore, a sedentary lifestyle was found to be associated with the increased incidence of ovarian cancer (RR = 1.29, 95%CI = 1.07–1.57)[8], breast cancer (RR = 1.20, 95%CI 1.10–1.30)[9], endometrial cancer (ORs, 1.28–1.36)[10], prostate cancer (RR = 1.07; 95%CI 0.99–1.16; P = 0.10)[11], colorectal cancer (ORs, 1.08–1.21)[12], and lung cancer (ORs, 1.21–1.27)[10]. As a kind of early-stage tumor, TNs may share similar biological mechanisms with cancers, thus, the existing evidence on the relationship between a sedentary lifestyle and cancer may also to some extent explain the impact of the sedentary lifestyle on TNs.

Implications and public health significance of the findings

Our findings provide additional evidence on the hazards of a sedentary lifestyle. Sedentary lifestyle has become a growing issue in modern society, especially since the COVID-19 pandemic. The adverse health effects caused by a sedentary lifestyle may become one of the long-term effects of COVID[27]. Preventive strategies are needed to alter the sedentary lifestyle among the population and improve public well-being. For the government staff, the health management center should promote the health education and healthy work patterns, especially among the high-risk groups.

Potential mechanisms of the association

In summary, the possible mechanisms underlying the increased prevalence of TNs included vitamin D and hormonal changes, metabolic dysfunction, and chronic low-level inflammation. Vitamin D deficiency and altered hormone levels were probably the most important mechanism. Epidemiological studies have found that a sedentary lifestyle was related to vitamin D deficiency due to limited sunlight exposure[28]. Vitamin D could regulate the function of thyroid as well as the release of TSH from the pituitary gland through vitamin D receptor[16]. Increased level of TSH following vitamin D deficiency was considered to stimulate the growth of thyroid cells, causing TNs and thyroid carcinoma[18]. In addition, with the vitamin D receptor and ossifying triol involved[29], vitamin D was related to the regulation of cell differentiation, apoptosis, and inflammation[30], all of which significantly contributed to the formation of TNs[31]. Metabolic dysfunction might a potential mediator on the pathway from the sedentary lifestyle to TNs [5] [32]. Nevertheless, more research would be needed to confirm or refute this hypothesis.

The inflammatory response is another potential pathway from the sedentary lifestyle to TNs. Previous studies have shown that sedentary people tended to have a higher concentration of inflammatory biomarkers such as C-reactive protein[19–23] which was considered to cause tumors through multiple pathways[33, 34]. In addition, inflammatory biomarkers may inhibit thyroid hormone synthesis, leading to an increased serum level of TSH[35] which was considered an independent predictor of TNs and thyroid carcinoma.

Modification effect of age

We found that the adverse effect of sedentary lifestyle was more pronounced in people of higher age. This finding was expected as the elderly tended to have a decreased ability to ingest materials, synthesize and process vitamin D[36] as well as a decreased function of metabolic system[37] and immune system[38]. In addition, the long-term sedentary lifestyle over previous years tended to cumulatively contributed to a higher vulnerability to TNs among the elderly. The results implied that medications targeted on the dysfunction of metabolic and immune systems such as vitamin D supplements may be an effective way to protect the elderly against the adverse impact of the sedentary lifestyle.

Association of sedentary lifestyle with the risk of TNs of different features

We found that the increased sedentary time was associated with a lower risk of TNs with blood flow signal. Similar studies were very limited, with only one suggesting that lack of exercise (as a surrogate of the sedentary lifestyle) was associated with less vascularity in TNs[39]. Given that blood flow signal usually represents a lower possibility of malignancy, this finding was consistent with the findings of our main analysis, suggesting that sedentary lifestyle may be more associated with TNs of low malignancy. We believe it would be reasonable to consider the sedentary lifestyle as a mild exposure which more likely to cause benign rather than malignant TNs. Our results indicated a positive association of sedentary lifestyle with TNs of all grades and features compared with the control group.

Strengths and limitations

The study has several strengths including that it used data from annual medical examination of government staff which have a higher quality than regular screening records. We focused on the public employees who were suffering a greater issue of sedentary lifestyle. However, some limitations should be acknowledged. Since all TNs were diagnosed based on ultrasound results and TI-RADS level but not based on biopsy, the malignancy of TNs could not be determined. The sedentary time was self-reported, which may lead to bias and only reflects approximate trends. However, the recall bias was acceptable, because most thyroid nodules do not have symptoms to affect their reports on sedentary time. Thyroid-related information such as that for TSH and 25 hydroxyvitamin D was not collected for interpretation of the mechanism. More data are needed to clarify the potential biological mechanisms and the potential causality between the sedentary lifestyle and TNs.

Our study discovered a significant association between sedentary lifestyle and TNs, with the strongest association being observed for TNs of TI-RADS2. Population over 50 years old were the most vulnerable. More studies on sedentary lifestyle and TNs are warranted to further examine the potential mechanisms and pathways.

Funding: The study was funded by the Guangzhou Cadre Health Management Center.

Disclosure Statement: The authors have nothing to disclose.

Competing Interests: The authors declare they have no financial interests.

Author Contributions: All authors contributed to the study conception and design. Material preparation and data collection were performed by Weizheng Zhang and Shuo Yang; bibliographic research and original draft preparation were performed by Peien Zhou and Hongli Zeng; conception, design, supervision of the manuscript were performed by Hui Zhou and Wangjian Zhang. The first draft of the manuscript was written by Peien Zhou and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the he Guangzhou Cadre Health Management Center. (Date 2022-03-01/No k2022-04).

Consent to participate: An informed consent was obtained from all participants included in the study.

Consent to publish: No individual data were published in this study.

Acknowledgments: The authors thank the participants, and the support by the Guangzhou Cadre Health Management Center.

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How was a sedentary lifestyle associated with the prevalence of thyroid nodules among government staff?

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