Current Iodine Nutrition Status and Prevalence of Thyroid Disorders in Tibetan Adults in an Oxygen-Deficient Plateau,Tibet,China: A Population-Based Study

Abstract

Background:

Iodine deficiency (ID) is a global problem in individuals living in an iodine-deficient environment, specifically in mountainous regions. However, data regarding the iodine nutritional status of Tibetan people in the plateau are limited.

Methods:

A population-based survey was conducted from July 2016 to July 2017 in Lhasa, Tibet, including 12 communities in Lhasa city and 10 surrounding rural areas. The iodine nutritional status of Tibetan people was evaluated using the traditional iodine nutrition indexes: urinary iodine concentration (UIC), thyroid size, serum thyroxine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody (TPOAb).

Results:

A total of 2295 healthy participants were screened, and 2160 participants who had completed all the required examinations were enrolled in this study (response rate, 94.1%). Urinary iodine showed a skewed distribution, with a median (upper and lower quartiles) of 154 (99–229) μg/L. The percentages of low iodine (UIC <100 μg/L), adequate iodine (UIC, 100–199 μg/L), and high iodine (UIC ≥200 μg/L) were 25.6%, 42.0%, and 32.4%, respectively. The urinary iodine level in the urban region was higher than that in the rural region (p < 0.05). Urinary iodine levels were lower with increasing age (p < 0.05). The prevalence of hyperthyroidism, hypothyroidism, goiter, TPOAb positivity, and thyroglobulin antibody positivity was 1.0%, 21.8%, 4.7%, 6.6%, and 10.4%, respectively. Logistic regression analysis found that urinary iodine was an independent risk factor for TPOAb positivity (odds ratio = 0.997 [95% confidence interval, 0.995–0.999]; p < 0.001).

Conclusions:

Compared with individuals living in the plains of China, Tibetan adults have a higher rate of ID. UIC was an independent risk factor for TPOAb positivity. This public health issue should be further investigated.

Introduction

Iodine is a key and essential component during the synthesis of thyroid hormones, including thyroxine (T4) and triiodothyronine (T3) in the thyroid gland. Iodine nutritional status, different from most micronutrients, is not restricted to individuals with good or poor diet but depends on the contents of iodine in the soil. Iodine deficiency (ID) is a global problem in individuals living in an iodine-deficient environment as a result of past glaciation, compounded by the leaching effects of snow, water, and heavy rainfall, which remove iodine from the soil (1). The mountainous regions of Europe (such as the Alps and the Apennines), northern Indian subcontinent, Andean region in South America, and lesser ranges of Africa are all iodine-deficient areas (1). China is a mountainous country that has extensive mountain ranges, where the Tibet Plateau, considered the highest plateau in the world, has an average elevation of 4000 m and is known as the “Roof of the World.” It has always been considered as one of the major regions of the world experiencing ID (1).

A large body of previous evidences has shown that ID impairs cognition and growth early in life (1 –5). Additionally, iodine status is also an important determinant of thyroid disorders in adults. Systematic reviews have confirmed the benefits of treating ID (5,6). Since 1996, China has implemented the universal salt iodization (USI) regulations to prevent iodine deficiency disorders (IDDs). And, Tibet also responded to the national policy and promulgated the “Salt Iodization Elimination of Iodine Deficiency Management Regulations.” To eliminate the harm of ID, long-term supply of iodized salt was adopted, and comprehensive prevention and control measures were supplemented by iodized oil pills and iodized tea bricks. And during 2000 to 2004, there was an important international financial support for iodized oil pills from Australia and World Health Organization (WHO). During these two decades, the incidence of cretinism and endemic goiter has decreased significantly (7), and the goal of eliminating ID has been successfully achieved as shown in a cross-sectional study enrolling 15,008 adult participants from 10 cities in China (8). As such, the international authorities declared that China has eliminated IDDs and its iodine status was more than adequate. However, almost all the studies regarding iodine nutritional status were conducted in inland plains. There were relatively few investigations regarding iodine nutritional status in the Tibet Plateau, which covers 12.5% of the area in China and is also considered as one of the major regions of the world experiencing ID.

In this study, the iodine nutritional status of Tibetan people in the plateau was evaluated using the traditional iodine nutrition indexes [urinary iodine concentration (UIC) (9), thyroid size, serum T4, thyrotropin (TSH), thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) (10)] to obtain the complete data of the current iodine nutritional status and prevalence of thyroid disorders in China, including the Tibet Plateau, and to provide sufficient evidence regarding the iodine nutritional status in high-altitude region in the world.

Materials and Methods

Study participants

A population-based survey was conducted from July 2016 to July 2017 in Lhasa, Tibet, China, at 3680 m above sea level, including 12 communities in Lhasa city and 10 surrounding rural areas of Lhasa city (Sanda, Cai'na, Zun Mucai, Tarong, Qiang'ge, Daga, Chagong, Menba, Doilungdêqên, and Qushui County). Participation was voluntary, and subjects were recruited through educational advertisements about this study. Participants with the following characteristics were included in the study: (i) Tibetan, (ii) older than 18 years, (iii) living at the survey site for more than 5 years, (iv) not taking iodine or thyroid drugs, (v) not receiving iodine-containing agents during the past three months, and (vi) nonpregnant or nonlactating women. This study was approved by the Medical Science Research Ethics Committee of the First Affiliated Hospital of China Medical University and was in accordance with the Declaration of Helsinki. All participants provided written informed consent for inclusion in the study, and they could withdraw from this study at any time. Participant survey flowchart is shown in Figure 1.

FIG. 1.

Flowchart of the survey. UIC, urinary iodine concentration.

Data collection

Participants were asked not to take foods with high iodine content (seafood, such as kelp, nori, and wakame) 1 week before sampling. The participants were fasting for more than 8 hours on the day before sampling. On the day of sampling, participants were given at least 30 minutes of rest, and 10 mL of morning urine and 10 mL of fasting venous blood were collected. Vacuum blood collection tubes (additives-free, glass material, applicable altitude: 4000 m; Jiangsu Kangjian Medical Apparatus Co. Ltd) were used for blood sampling. The venous blood specimens were set to stand for coagulation and then centrifuged at 3000 rpm for 10 minutes on-site (Medical centrifuge BY-160C, Beijing Baiyang Centrifuge Co., Ltd, Beijing, China), and serum was extracted. Thyroid ultrasound was performed using a GE LOGIQ α 100 color Doppler ultrasound system (General Electric, Medical System (China) Co., Ltd, Wuxi, Jiangsu), with a transducer probe frequency of 7.5 MHz. Participants assumed a supine position and fully exposed their anterior neck area, and a lubricant was evenly applied. The size of the gland was measured, and the length, width, and thickness of the thyroid were measured in millimeters.

Laboratory methods

Due to the limitations of the Lhasa laboratory inspection equipment, to ensure the accuracy of urinary iodine and thyroid function, the collected morning urine and serum were immediately sealed into the specimen box and placed in a −20°C freezer, and all specimens were transported by refrigeration to the “National Thyroid Disease Investigation Project Laboratory” to conduct unified measurements. UIC was measured by plasma mass spectrometry (ICP-MS, Agilent 7700x; Agilent Technologies). We used certified reference material (CRM) for UIC analysis. The CRM (GBW09108, GBW9109, and GBW9110) was from the Chinese Center for Disease Control and Prevention (CDC), and the results measured by the central laboratory were 70.8 ± 9.0, 143 ± 10, and 224 ± 14 μg/L, respectively. The within-run coefficient of variance (CV) was 2.3%, 2.5%, and 2.4%, while the between-run CV was 2.7%, 1.4%, and 2.3%, respectively, in our central laboratory. TSH, free T4 (fT4), free T3 (fT3), TPOAb, and TGAb were measured by immunochemiluminometric assay (Roche Cobas e601; Roche Diagnostic, Switzerland).

Urinary iodine classification standard

According to the WHO, urinary iodine level <100 μg/L is insufficient iodine intake (urinary iodine level <20 μg/L for severe ID, 20–49 μg/L for moderate ID, 50–99 μg/L for mild ID), 100–199 μg/L adequate iodine intake, 200–300 μg/L more than adequate iodine intake, and >300 μg/L excessive iodine intake (11).

Diagnosis of goiter

The diagnosis of goiter was established according to the results of thyroid ultrasound. The thyroid volume was calculated using the ellipse correction method according to the following formula recommended by the WHO: thyroid volume (mL) = (length × width × thickness × 0.479)/1000, where the sum of the left and right lobe volume is the total volume of the thyroid (12). The diagnostic criteria for goiter were total volume >18.0 mL for adult female and total volume >25.0 mL for adult male.

Evaluation of thyroid function

The evaluation of the thyroid function included three steps. First, TSH, TPOAb, and TGAb levels were measured in all the participants. Second, when the TSH value exceeded the normal range, fT4 level was further measured. When TSH was lower than the normal range, fT4 and fT3 levels were further measured. The reference ranges of thyroid function were based on the Roche's reference intervals: TSH reference value, 0.27–4.20 mIU/L; fT3 reference value, 3.1–6.8 pmol/L; fT4 reference value, 12–22 pmol/L; TPOAb reference value, 0–34 IU/L; and TGAb reference value, 0–50 IU/L.

Statistical analysis

The skewed distribution measurement data are expressed by the median (upper and lower quartiles) [M (QR)], and logarithmic transformation of skewed distribution data was performed. Pairwise comparison was performed using independent sample T-test, multiple sets of data using one-way analysis of variance, and categorical variables using chi-squared test. All tests were two-sided, and the difference was statistically significant if p < 0.05. The Statistical Package for the Social Sciences version 23.0 software (IBM Corp., Armonk, NY) was used in data processing and statistical analysis.

Results

Clinical characteristics of the study population

A total of 2295 healthy participants were screened, and 2160 participants who had completed all the required examinations, including UIC, thyroid function, and thyroid ultrasound examinations, were enrolled in this study (response rate, 94.1%). The clinical characteristics of all the participants are shown in Table 1. The average age of the participants was 41 ± 16 years, 64.6% were females, and 83.1% lived in urban areas. The M (QR) of UIC was 154 (99–229) μg/L. The prevalence of goiter, hypothyroidism, and hyperthyroidism was 4.7%, 21.8%, and 1.0%, respectively.

Table 1.

Characteristics of the Study Population

Baseline characteristics	Total	Normal^a	Goiter	Hypothyroidism	Hyperthyroidism
n	2160	1422 (65.8%)	102 (4.7%)	470 (21.8%)	22 (1.0%)
Male/female	764/1396	568/854	13 (1.7%)^b/89 (6.4%)^c	142 (18.6%)^b/328 (23.5%)^c	8 (1.0%)^b/14 (1.0%)^c
Age (years), mean ± SD	41 ± 16	39 ± 15	52 ± 15	45 ± 15	53 ± 14
BMI (kg/m²), mean ± SD	23.8 ± 5.4	23.5 ± 4.4	24.1 ± 4.4	25.1 ± 7.9	24.5 ± 4.3
Region (urban/rural)	1795/365	1206/216	89/13	380/90	15/7
UIC (μg/L)	154 (99–229)	161 (102–239)	143 (82–195)	148 (100–208)	155 (92–253)
fT3 (pmol/L) (n = 22)	—	—	—	—	5.7 (4.9–6.6)
fT4 (pmol/L) (n = 492)	—	—	—	15.0 (13.5–16.7)	19.3 (15.1–26.1)
TSH (mIU/L)	2.4 (1.6–3.9)	2.1 (1.5–2.9)	1.2 (0.7–2.2)	5.9 (5.0–8.0)	0.1 (0–0.2)
TPOAb (IU/L)	11.6 (9.4–15.2)	11.1 (9.2–13.9)	12.0 (9.7–15.5)	12.1 (9.8–17.3)	13.7 (10.0–19.3)
TGAb (IU/L)	13.6 (11.1–18.1)	12.8 (10.8–16.0)	15.6 (12.4–21.9)	14.2 (11.4–24.2)	18.3 (15.6–26.4)

UIC, fT3, fT4, TSH, TPOAb, and TGAb are expressed as median (interquartile range).

Participants with normal TSH and thyroid ultrasound, negative TPOAb and negative TGAb.

The prevalence of the disease in male participants.

The prevalence of the disease in female participants.

BMI, body mass index; fT3, free triiodothyronine; fT4, free thyroxine; SD, standard deviation; TGAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody; TSH, thyrotropin; UIC, urinary iodine concentration.

Urinary iodine distribution and associated factors

The urinary iodine levels of Tibetan adults in Lhasa showed a skewed distribution, and the M (QR) was 154 (99–229) μg/L. The prevalence of ID was 25.6% (including mild ID, moderate ID, and severe ID, 18.7%, 5.6%, and 1.3%, respectively). The prevalence of adequate, more than adequate, and excessive iodine was 42.0%, 20.8%, and 11.6%, respectively (Table 2).

Table 2.

Distribution of Urinary Iodine Concentration by Sex, Region, and Age

UIC (μg/L)			UIC range					t/F	p-Value
UIC (μg/L)			<50	50–99	100–199	200–299	≥300
	n (%)	M (QR)	n (%)	n (%)	n (%)	n (%)	n (%)
Sex
Male	764 (35.4)	153 (97–221)	63 (8.2)	139 (18.2)	327 (42.8)	157 (20.6)	78 (10.2)	−1.398	0.162
Female	1396 (64.6)	155 (100–231)	86 (6.2)	264 (18.9)	581 (41.6)	293 (21.0)	172 (12.3)	−1.398	0.162
Region
Urban	1795 (83.1)	158 (101–232)	119 (6.6)	324 (18.1)	740 (41.2)	395 (22.0)	217 (12.1)	3.201	0.001
Rural	365 (16.9)	140 (90–197)	30 (8.2)	79 (21.7)	168 (46.0)	55 (15.1)	33 (9.0)	3.201	0.001
Age
Youth (18–44 years)	1249 (57.8)	174 (116–256)	52 (4.2)	185 (14.8)	498 (39.9)	320 (25.6)	194 (15.5)	74.302	0.000
Middle (45–59 years)	599 (27.7)	136 (92–198)	45 (7.5)	139 (23.2)	269 (44.9)	98 (16.4)	48 (8.0)
Elderly (≥60 years)	312 (14.5)	114 (68–164)	52 (16.7)	79 (25.3)	141 (45.2)	32 (10.3)	8 (2.6)
Total	2160 (100)	154 (99–229)	149 (6.9)	403 (18.7)	908 (42.0)	450 (20.8)	250 (11.6)

Logarithmic transformation of urinary iodine data, pairwise comparison using independent sample T test, t for test statistic, multiple sets of data using one-way ANOVA, F for test statistic.

ANOVA, analysis of variance; M (QR), median (upper and lower quartiles).

The urinary iodine level was similar between females and males (155 [100–231] vs. 153 [97–221] μg/L, χ ² = −1.398, p = 0.162) but significantly higher in participants living in the urban region than those living in rural regions (158 [101–232] vs. 140 [90–197], χ ² = 3.201, p = 0.001). Subsequently, we divided the whole population into three groups according to age, and we found that with the higher age, urinary iodine levels were lower (F = 74.302, p ≤ 0.001).

Prevalence of thyroid goiter and the distribution of thyroid function

The prevalence of goiter was 4.7% as shown in Table 3. The prevalence of goiter was higher in females (6.4%) than in males (1.7%) (χ ² = 23.973, p < 0.001). The prevalence of goiter was not significantly different between the urban (5.0%) and rural (3.6%) areas (χ ² = 1.315, p = 0.252). With higher age, the prevalence of goiter was higher (χ ² = 45.169, p < 0.001).

Table 3.

Prevalence of Goiter by Sex, Region, and Age

Goiter	Sex		Region		Age			Total
	Male	Female	Urban	Rural	Youth (18–44 years)	Middle (45–59 years)	Elderly (≥60 years)	Total
	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Yes	13 (1.7)	89 (6.4)	89 (5.0)	13 (3.6)	27 (2.2)	45 (7.5)	30 (9.6)	102 (4.7)
No	751 (98.3)	1307 (93.6)	1706 (95.0)	352 (96.4)	1222 (97.8)	554 (92.5)	282 (90.4)	2058 (95.3)
Total	764 (100)	1396 (100)	1795 (100)	365 (100)	1249 (100)	599 (100)	312 (100)	2160 (100)
χ ²	23.973		1.315		45.169
p-Value	0.000		0.252		0.000

Categorical variables using chi-square test, χ ² for test statistic.

According to the distribution of thyroid function, all the 2160 participants completed the TSH, TPOAb, and TGAb measurements, 492 completed the fT4 assay, and 22 completed the fT3 assay. As summarized in Table 4, the levels of TPOAb and TGAb were significantly higher in females than in males (both p < 0.001). The level of TPOAb was higher in rural area than in urban area (p = 0.003). With higher age, the level of TGAb was higher (p < 0.001).

Table 4.

Distribution of Thyroid Function by Sex, Region, and Age

	TSH (mIU/L, n = 2160)	fT4 (pmol/L, n = 492)	fT3 (pmol/L, n = 22)	TPOAb (IU/L, n = 2160)	TGAb (IU/L, n = 2160)
Total	2.4 (1.6–3.9)	15.1 (13.5–16.8)	5.7 (4.9–6.6)	11.6 (9.4–15.2)	13.6 (11.1–18.1)
Sex
Male	2.3 (1.6–3.6)	16.1 (14.5–18.4)	5.9 (5.0–7.2)	11.0 (9.1–14.4)	12.9 (10.8–16.1)
Female	2.5 (1.6–4.1)	14.6 (13.2–16.3)	5.6 (4.8–6.6)	11.8 (9.5–15.6)	14.1 (11.3–19.6)
T	−2.666	5.151	0.502	−4.531	−7.874
p-Value	0.008	0.000	0.621	0.000	0.000
Region
Urban	2.4 (1.6–3.9)	15.1 (13.6–16.6)	5.7 (4.8–6.3)	11.3 (9.2–14.8)	13.5 (11.0–18.1)
Rural	2.4 (1.4–4.2)	14.8 (13.2–17.9)	5.9 (5.0–8.3)	12.8 (10.5–16.8)	14.2 (11.8–18.5)
t	0.373	−0.756	−0.202	−2.981	−1.165
p-Value	0.709	0.451	0.842	0.003	0.244
Age
Youth (18–44 years)	2.4 (1.7–3.5)	15.3 (13.7–17.3)	4.6 (4.3–8.7)	11.0 (9.1–14.2)	12.8 (10.7–16.8)
Middle (45–59 years)	2.5 (1.5–4.9)	14.9 (13.3–16.6)	5.7 (5.3–7.5)	12.6 (10.1–17.2)	15.0 (12.1–21.3)
Elderly (≥60 years)	2.6 (1.7–4.4)	15.0 (13.1–16.6)	6.0 (4.8–6.8)	11.9 (9.4–15.6)	14.6 (12.2–19.3)
F	2.249	0.628	0.293	17.813	14.226
p-Value	0.106	0.534	0.750	0.000	0.000

TSH, fT4, fT3, TPOAb, and TGAb are expressed as median (interquartile range).

Logarithmic transformation of urinary iodine data, pairwise comparison using independent sample T test, t for test statistic, multiple sets of data using one-way ANOVA, F for test statistic.

Urinary iodine and prevalence of thyroid disorders

The prevalence of TPOAb positivity decreased gradually with the higher UIC (χ ² = 26.777, p < 0.001) as shown in Table 5. However, the prevalence of overt/subclinical hyperthyroidism, overt/subclinical hypothyroidism, TGAb positivity, and goiter was not significantly different among each urinary iodine group (p > 0.05). Using TPOAb positivity as a dependent variable and urinary iodine as an independent variable, after adjusting for age, sex, and body mass index, multivariate logistic regression found that urinary iodine was an independent risk factor for TPOAb positivity (odds ratio [OR] = 0.997 [95% confidence interval, CI 0.995–0.999]; p < 0.001).

Table 5.

Prevalence of Thyroid Diseases in Different Urinary Iodine Groups

Thyroid disorders	Total (2160)	Insufficient (n = 552)	Adequate (n = 908)	More than adequate (n = 450)	Excessive (n = 250)	χ²	p-Value
Thyroid disorders	Total (2160)	(<100 μg/L)	(100–199 μg/L)	(200–299 μg/L)	(≥300 μg/L)	χ²	p-Value
Overt hyperthyroidism	8 (0.4)	1 (0.2)	3 (0.3)	1 (0.2)	3 (1.2)	5.506	0.138
Subclinical hyperthyroidism	14 (0.6)	6 (1.1)	6 (0.7)	0 (0)	2 (0.8)	4.678	0.197
Overt hypothyroidism	51 (2.4)	15 (2.7)	25 (2.8)	9 (2.0)	2 (0.8)	3.807	0.283
Subclinical hypothyroidism	419 (19.4)	102 (18.5)	199 (21.9)	74 (16.4)	44 (17.6)	7.009	0.072
TPOAb+	143 (6.6)	56 (10.1)	66 (7.3)	15 (3.3)	6 (2.4)	26.777	0.000
TGAb+	224 (10.4)	61 (11.1)	100 (11.0)	37 (8.2)	26 (10.4)	2.913	0.405
Goiter	102 (4.7)	33 (6.0)	44 (4.8)	16 (3.6)	9 (3.6)	4.028	0.259

Categorical variables using chi-square test, χ ² for test statistic.

All values are expressed as n (%).

Discussion

In this population-based study, we found that the urinary iodine levels of Tibetan adults in Lhasa were 154 (99–229) μg/L. The percentages with low iodine (UIC <100 μg/L), adequate iodine (UIC 100–199 μg/L), and high iodine (UIC ≥200 μg/L) were 25.6%, 42.0%, and 32.4%, respectively. The prevalence of hyperthyroidism, hypothyroidism, goiter, TPOAb positivity, and TGAb positivity was 1.0%, 21.8%, 4.7%, 6.6%, and 10.4%, respectively. Moreover, we also found that UIC was an independent risk factor for TPOAb positivity (OR = 0.997 [CI 0.995–0.999]; p < 0.001).

Since 1996, China has implemented the USI regulations to prevent IDDs. Subsequently, UIC levels significantly changed according to subsequent iodine nutrition surveys. At the beginning of the mandatory salt iodization program in 1995, the median UIC was 165 μg/L. Considering the occurrence of iodine excess in 1997 (median UIC, 330 μg/L) and 1999 (median UIC, 306 μg/L), the Chinese central government revised the national salt iodization task in 2002. The iodine level was reduced to 241 μg/L in 2002 and 246 μg/L in 2005 (13), after adjusting the salt iodine content again in 2012, a recent survey in China in 2016 showed that the UIC level was 205 μg/L (8). However, in the abovementioned national surveys, Tibetan adults were not included and nor was the study conducted in Tibet area. Hence, this study is the first one to report the iodine status in Tibetan adults in Tibet using UIC level.

We found that the average urinary iodine level was 154 (99–229) μg/L in Tibetan adults, which was significantly lower than that of the current average of other mainland plains in China while similar to that when China first started implementing the mandatory salt iodization program in 1995. We found that the population with low iodine (UIC <100 μg/L) was 25.6%. According to Teng's research in 10 low-altitude cities in China, the population with urinary ID was 15.7% (8). Thus, the iodine nutritional level of Lhasa adult Tibetans is significantly lower than that of individuals living in mainland China.

Tibet belongs to the plateau region in the world. Compared with other plateau regions, a meta-analysis of the Brazilian plateau found that the ID population is between 24% and 32% (14). Additionally, according to the study in the highlands of Mexico with an altitude of 600–2700 m, 19.5% of individuals with ID were noted (15). It may be observed that because of the special characteristics of the environment in high-altitude areas, that is, they are iodine-deficient areas, ID is significantly experienced by dwellers, which is consistent with the result of our study, that is, that the proportion of ID in Tibet is relatively high.

The relatively high proportion of iodine-deficient people in Tibet may be due to the following reasons: (i) From a geographical point of view, as mentioned earlier, the Himalayas in Tibet, European Alps, and South American Andes in the same area were considered the major regions experiencing ID due to the insufficient iodine present in these areas (1). Iodine insufficiency is the most important reason for the high proportion of individuals with ID in the Tibetan Plateau. (ii) It may also be related to the eating habits of the Tibetan people in the plateau. The main traditional food is highland barley, accounting for about 60% of the grain in Tibet, with iodine content of 4 μg/100 g. The meat products in traditional diet are mainly Yak meat, with iodine contents of 8.6 μg/100 g. Although in 1998, the government allocated land without compensation to establish iodized salt factory in Tibet, and iodized salt coverage in Tibet increased from 19.0% in 1997 to 97.4% in 2016 (16), some Tibetans still did not consume salt in the market but used local Tibetan homemade salt (the salt made by drying the high salty river water), specifically some of the farmers in remote areas and herdsmen and temple monks we investigated. (iii) Considering the special environmental anoxic factors in the plateau, the bodies of the Tibetans experience oxygen deficiency for a long time. There is no relevant literature report yet that assesses the effects of iodine metabolism in the oxygen-deficient environment. Hence, this should be investigated in the future.

In this study, we also found that lower UIC with increasing age, which is consistent with the results of previous studies (17). Considering that the body's iodine is mainly from diet, the food intake of the elderly is smaller and the diet is lighter than that of the youth, hence reducing the intake of iodized salt, and some studies suggest that it may be related to malnutrition in the elderly (18). Concurrently, with the increase of age, estimated glomerular filtration rate (eGFR) gradually decreases, decreasing urinary iodine excretion; thus, iodine measurement is low, but there is still insufficient research on the association between urinary iodine and eGFR.

The urinary iodine level in urban areas was (158 [101–232] μg/L) higher than that in rural areas (140 [90–197] μg/L). From the distribution law of iodine, the urinary iodine level in mountainous area is less than that of the plain area, and the rural area is at a higher altitude than the urban area, and its iodine content is lower than that of the urban. In rural areas, the diet structure is not urban-diversified, thus reducing the chances of iodine intake (19). Also, some studies have also found that (20) educational level is also a factor of urinary iodine. The higher the educational level, the closer the urinary iodine is to the normal level. The educational level in rural areas is generally lower than that in urban areas.

The prevalence of hypothyroidism, hyperthyroidism, and TGAb positivity in this study was similar to that reported by Teng and colleagues in 2016 (8), while the proportion of TPOAb positivity (6.6%) was significantly lower than that reported in 2016 (11.5%). Our study also found that the prevalence of goiter is 4.7%, this result is close to that of 1995 (5.02%) when China started the mandatory salt iodization program, but higher than that in the study by Teng and colleagues in 2016, which included 10 low-altitude cities in China (2.9%) (8). Goiter is closely associated with ID because ID will hinder the synthesis of thyroid hormone, which results in increased TSH secretion, resulting in abnormal thyroid growth (21,22). The prevalence of goiter in school-age children is a more appropriate tool to assess iodine nutrition than in adulthood due to its sensitivity to iodine (11). So the limitation of this study was that we did not evaluate the prevalence of goiter in school-age children. Another limitation was that the UIC was measured from a spot urine sample and that may lead to bias.

The prevalence of goiter was higher in females (6.4%) than in males (1.7%), which is consistent with the results of previous studies (23) because of the following probable reason: thyroid growth factor is susceptible to sex hormones such as estrogen (24), and females are diagnosed more commonly with autoimmune thyroid diseases than males (25,26). With the increase of age, the prevalence of goiter was higher. It may also be related to the elderly's UIC being lower than those that are younger, and ID is associated with goiter or it could also due to hypothyroidism being more frequent in the elderly (27).

TSH, fT4, TPOAb, and TGAb all showed differences by sex. TSH was slightly higher in females than in males, and fT4 was slightly higher in males than in females, which is consistent with the results of previous studies (28,29). The association between sex and TSH and thyroid hormone may be related to estrogen regulation (30). TPOAb and TGAb were higher in females than in males, and TPOAb and TGAb associated with autoimmune thyroid disease (31). Furthermore, it is worth noting that between the age groups, TPOAb and TGAb are statistically different, and the most prominent in the middle-aged group may be due to the sudden changes in estrogen in women during menopause, which may affect the changes of TPOAb and TGAb in the middle-aged group. The previous studies have also shown that positive antibodies peak at 45–55 years old (32). However, the specific mechanism is unknown and needs to be investigated in the future.

We found that TPOAb was associated with UIC, lower UIC was associated with higher prevalence of TPOAb positivity. This finding is inconsistent with the current view that excessive intake of iodine leads to an increase in the positive rate of thyroid autoantibodies (33 –35). This discrepancy may be due to the following: (i) Whether iodine will aggravate or induced thyroid autoimmune diseases is still controversial, and the focus of the controversy is mainly on whether iodine supplementation has changed the thyroid immune markers, and there are different findings that iodine does not always cause thyroid autoimmunity, consistent with the results in the studies conducted in India (36) and Morocco (37). Some studies found that urinary iodine is not associated with thyroid autoimmunity after iodine supplementation. (ii) A cohort study conducted by Terpling and colleagues reported that increased levels of thyroid antibodies are associated with genetic and environmental factors in the population (38). The selected populations include high-altitude and high-cold Tibetan adults in Lhasa. Due to the differences in diet structure, genetic background, and environmental factors, the physiological functions of the body are significantly different from those in the plain area, which may be the reason for discrepant results in this study.

In conclusion, in this population-based study, compared with the individuals living in the plains of China, Tibetan adults have a higher rate of ID. UIC was an independent risk factor for TPOAb positivity. This public health issue should be further investigated and direct effort for iodine supplementations initiatives.

Footnotes

Acknowledgments

We thank all the participants in the study. We also thank the Institute of Endocrinology, China Medical University, for their help during the survey, measurements of UIC and thyroid function.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This research was supported by the Research Fund for Public Welfare from National Health and Family Planning Commission of China (Grant No. 201402005), and the Special Scientific Research Fund of Clinical Medicine of Chinese Medical Association (15010010589).

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