Impact of micronutrient status on thyroid function in adolescent Afghan refugees; a cross-sectional study

Impact of micronutrient status on thyroid function in adolescent Afghan refugees; a cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of micronutrient status on thyroid function in adolescent Afghan refugees; a cross-sectional study Saima Shaheen, Muhammad Shahzad, Nabila Sher, Muhammad Shabbir Khan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5349851/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Jun, 2025 Read the published version in Thyroid Research → Version 1 posted 10 You are reading this latest preprint version Abstract Micronutrients play crucial role in several metabolic processes including thyroid hormone metabolism and functions. The current study aimed to assess the associations between thyroid hormone levels and micronutrient status in a cohort of adolescents Afghan refugees residing in a refugee camp in Pakistan. A randomised, community based, cross-sectional study design was employed to recruit 206 adolescent (both male and female) Afghan refugees aged 10–19 years. Sociodemographic data, anthropometric assessments and blood samples were collected using standard methods. Serum vitamins, minerals and thyroid hormones levels were assessed using ELISA, electrochemiluminescence and inductively coupled plasma mass spectrometry (ICP-MS) respectively. Overall results showed the median levels of T3 and TSH were significantly higher (p < 0.05) in younger adolescents (10–14 years) compared to 15–18 years old while T4 significantly higher in boys compared to girls. Correlational analysis between serum micronutrients status (vitamin D, vitamin B12, ferritin, folate, zinc, copper, selenium) and thyroid hormones revealed significant relationship in different age groups. Overall, vitamin D exhibits a statistically significant positive correlation with T4 (r = 0.279) in the combined, younger (r = 0.277) and older (r = 0.319) age groups. In contrast, a statistically significant but negative correlation was observed when zinc levels were compared with T3 (r=-0.288) in the older age group and with T4 (r=-0.195) in the younger age group. In conclusion, micronutrients status especially vitamin D and zinc have important implications for thyroid health thereby requiring close monitoring of any thyroid deficiency related disorders in vulnerable population such as refugees. Clinical trial number: Not applicable Figures Figure 1 Introduction Micronutrient deficiencies are generally caused by inadequate intake of essential micronutrients (vitamins and minerals) and represent a major global public health burden. This problem is largely limited to developing nations and socioeconomically disadvantaged populations. Estimated reports from the World Health Organization (WHO) indicate that over 2 billion people worldwide suffer the physiological consequences of micronutrient insufficiency [ 1 ]. Micronutrient insufficiencies are widespread causes of suppressed immune function, disturbed metabolism, impaired physical and cognitive development in children, and increased risk of chronic conditions such as cancer and cardiovascular diseases [ 2 , 3 ]. Optimal metabolism in humans is predicated on adequate supplies of micronutrients that act as enzyme cofactors and structural components for macromolecules. One of the major human-health impacts of micronutrient availability is thyroid metabolism and function [ 4 – 6 ]. In humans, the thyroid gland plays an important role in growth and development through maintenance of homeostasis and supporting the normal function of the cardiovascular, reproductive and nervous systems [ 7 ]. Thyroid function is primarily regulated by the hypothalamic-pituitary-thyroid axis through the action of thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine [T4]. Thyroid hormones are crucial for cellular development, differentiation, growth, and regulation of protein, lipid and carbohydrate metabolism in nearly all tissues [ 8 ]. Thyroid hormone signaling is also essential for normal growth and maturation of organs such as the brain, lung, heart, skeletal muscle and bone. However, the production of inappropriate amounts of thyroid hormones results in hypothyroidism or hyperthyroidism which have devastating consequences on human health. Hyperthyroidism causes weight loss, heat intolerance and rapid heartbeat (tachycardia) while hypothyroidism is characterized by weight gain, feeling cold (cold intolerance), constipation, enlargement of the thyroid gland (goiter) and slowed metabolism (metabolic disruptions) [ 9 ]. Although the exact etiology and pathogenesis of thyroid disorders is not known, a role for micronutrients and trace elements is frequently suggested [ 10 ]. Several micronutrients, especially trace elements, are found in higher concentration in the thyroid gland than in any other tissue in the body [ 10 , 11 ] and are essential for thyroid hormone synthesis, metabolism and function. Micronutrient status is also a key determinant of risk and severity of autoimmune thyroid disorders (AITD) as both micronutrient deficiency and excess can promote autoimmune attack on the thyroid gland. Indeed, epidemiological studies indicate an increased susceptibility to pathogenic thyroid dysfunction is linked to the dietary availability of the micronutrients iodine, iron, selenium, copper, zinc, and vitamins B12 and D [ 4 ]. Selenium (Se) is a constituent of three iodothyronine deiodinase enzymes that catalyze the conversion of prohormone thyroxine (T4) to the active hormone 3,3′,5-triiodothyronine (T3). Thus, Se plays a direct role in the metabolism and activation of thyroid hormones ([ 12 , 13 ]. Se deficiency has been repeatedly associated with increased risk of AITD, such as Graves’ disease and Hashimotos’s thyroiditis, and is also linked with exacerbated developmental hypothyroidism primarily caused by iodine deficiency [ 14 ]. Zinc is another essential micronutrient with a well-established role in thyroid hormone biosynthesis, metabolism and signaling. Zn is an essential structural component and catalytic cofactor for numerous enzymes involved in thyroid hormone biosynthesis [ 15 ], playing a role in thyrotropin-releasing hormone (TRH) production. TRH stimulates release of thyroid stimulating hormone (TSH) from the pituitary, which in turn acts on the thyroid to promote thyroid hormone production [ 16 ]. In-vivo studies in animal models demonstrate that inadequate zinc levels impair thyroid hormone production, potentially causing hypothyroidism, developmental abnormalities and compromised immunity [ 17 ]. Thyroid hormones are also reported to modulate Zn homeostasis by regulating its intestinal absorption and renal reabsorption in rats [ 18 ]. In humans, the finding of a strong correlation between tissue levels of thyroid hormones and zinc suggests an intimate bidirectional relationship between the two [ 19 , 20 ]. Furthermore, zinc supplementation in humans results in a significant increase in plasma TSH, T3 and T4 levels [ 21 ]. Although, the impact of micronutrients on thyroid functions has been frequently reported in the literature, such studies have been mostly focused on thyroid disease patients, children, and pregnant women [ 22 , 23 ]. Until now, little or no research investigating the relationship between micronutrient status and thyroid function has been conducted in populations that are at high risk of malnutrition, such as refugees. Therefore, this cross-sectional study aimed to investigate the associations between thyroid hormone levels and micronutrient status in a cohort of adolescents Afghan refugees residing in a refugee camp in Pakistan. Methods Study design and population This cross-sectional study analysed 206 adolescent (both male and female) Afghan refugees (aged 10–19 years) residing in Khazana refugee camp, the largest refugee camp (5000 residents) in Peshawar, Pakistan. They were recruited by a non-probability, consecutive sampling method in a study assessing the nutritional status of apparently healthy adolescents [ 24 ]. Participants with missing variables in the questionnaire data (n = 2) or plasma micronutrients data (n = 17) or thyroid hormones (n = 16) were excluded from analysis. A final sample of 182 participants (91 boys and 91 girls) were included in the analysis. An information sheet containing the detailed procedures and purpose of the study in an easy to understand, local language (Pashto and Dari) was provided to all the participants before signing a written informed consent. Ethical and administrative approval for the study was provided by Khyber Medical University and the Peshawar Afghan Commissionerate (Peshawar), respectively. Data and samples collection Participant demographic and socioeconomic status information was collected by an interviewer administered, structured questionnaire. Trained data collectors measured the height and weight of the participants using standard procedures. The body mass index (kg/m 2 ) was calculated using the participants’ height and weight. Blood samples were collected from the participants between 08:00–10:00 am. Plasma and serum were separated, transported to the main lab within 4 hours and stored at -80°C prior to analysis. Laboratory assays Complete blood counts were performed on freshly collected whole blood samples using a Sysmex automatic haematology analyzer (XP-100, Jalan Tukang, Singapore). Vitamin D status was assessed using a 25-OH vitamin D Diasorin radioimmunoassay ELISA kit (Euroimmun, Germany) while ferritin, vitamin B12 and folate were assessed using the Abbott Architect i2000 analyser (Abbott Diagnostics, Zug, Switzerland). Thyroid function tests were performed to measure the serum levels of total T3, T4 and thyroid stimulating hormone (TSH) using an Elecsys electrochemiluminescence based assay on a Cobas e 411 analyser (Roche Diagnostics, Germany). The levels of iron, zinc, selenium and copper were determined by reconstituting freeze-dried plasma samples in Milli-Q (18 MΩ) water and subjecting it to inductively coupled plasma mass spectrometry analysis (ICP-MS; Thermo Fisher Scientific iCAPQ, Bremen, Germany). Statistical Analysis Age is reported as mean (SD) and age categories, educational status, family size and female household head educational status are reported as frequencies (percentage). Thyroid hormone (T3, T4 and TSH) data were categorized into tertiles. Micronutrient concentrations are described as medians (Q1 and Q3) by tertiles for T3, T4 and TSH. Quantile regression was used to investigate association among thyroid hormones (T3, T4 and TSH) and basic characteristics (age, gender and BMI). Due to non-normal distribution of the micronutrient levels, the linear trends of these biomarkers across ordered categories of thyroid hormones (T3, T4 and TSH) were assessed using the Jonckheere Terpstra Test. Correlation between biomarkers and thyroid hormones were assessed using Spearman rank correlation. All data analysis was conducted using SAS Version 9.4. Results General characteristics of the study participants General characteristics of the 206 study participants, 103 males and 103 females are presented in Table 1 . Participants were divided into two age groups, 10–14 (63.7%) and 15–19 (36.3%) years. Background characteristics of the study participants were described previously and are thus provided here in supplementary Table S1 . Table 1 Association of thyroid hormone levels with age, sex and BMI Characteristics T3 T4 TSH All ages Age (Categories) 0.22 (0.05, 0.43) * 0.2 (-0.75, 0.81) 0.46 (0.01, 0.74) * Sex (Gender = 1) 0.12 (-0.01, 0.26) 1.29 (0.64, 1.94) * 0.07 (-0.27, 0.34) BMI (kg/m 2 ) 0.001 (-0.04, 0.03) 0.1 (-0.08, 0.2) 0.04 (-0.03, 0.11) Age Group (10–14 Years) Sex (Gender = 1) 0.18 (0, 0.29) ** 1.32 (0.36, 2.04) * -0.11 (-0.47, 0.42) BMI (kg/m 2 ) 0.02 (-0.04, 0.04) 0.17 (-0.06, 0.37) 0.08 (-0.04, 0.13) Age Group (14–19 Years) Sex (Gender = 1) 0.16 (-0.33, 0.29) 1.26 (0.15, 2.21) * 0.29 (-0.05, 0.59) BMI (kg/m 2 ) -0.01 (-0.07, 0.02) 0.001 (-0.18, 0.19) -0.01 (-0.09, 0.05) Coefficient estimates with 95% CI from quantile regression modeling median of T3, T4 and TSH to investigate association with age, sex and BMI. * p-value < 0.05, **p-value = 0.05 Association between demographic and nutritional status, and thyroid function biomarkers We first assessed whether there is any relationship between demographic characteristics (age, gender), nutritional status (BMI) and median levels of thyroid hormones among the participants (Table 1 ). Overall, the results show that median levels of T3 and TSH are significantly higher in 10–14 years as compared to 15–18 years. Although, no significant association was observed for median levels of T4 with age, its concentration was significantly higher in boys compared to girls. Stratified analysis by age groups showed that T4 levels are significantly higher among boys in both age groups while T3 was high only younger adolescent group (10–14 years). However, no significant association was observed between thyroid hormones level and BMI (Table 1 ). Association between plasma micronutrients levels and thyroid function biomarkers To assess the association of selected micronutrients with thyroid function biomarkers, the median concentration of the micronutrients was divided into three equivalently sized tertiles based on serum T3, T4 and TSH levels. No statistically significant trend was observed between serum micronutrient levels across the three tertiles based on serum T3 levels (Table 2 ). However, stratified analysis by age showed a significantly decreasing trend in serum ferritin and zinc levels from across tertile 1 – Table 2 Comparison of micronutrientstatus and T3 levels in adolescent Afghan refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to T3 levels. Characteristics T3 Overall Tertile 1 Tertile 2 Tertile 3 P-trend Median (Q1, Q3) of T3 1.05 (0.93, 1.16) 1.42 (1.33, 1.51) 1.79 (1.67, 2.06) All age groups Ferritin (ng/mL) 39 (27, 61.4) 48.0 (29.5, 79.6) 35.0 (24.6, 49.0) 40.6 (26.54, 59.45) 0.09 Folate (ng/mL) 4.4 (3.4, 6.1) 4.6 (3.1, 6.6) 4.3 (3.6, 5.8) 4.2 (3.6, 6) 0.82 Vitamin B12 (pg/mL) 219 (157, 348) 228 (167, 392) 220.0 (155.0, 349.0) 205.0 (161.0, 300.0) 0.29 Vitamin D (ng/mL) 22.3 (16.2, 27.5) 20.4 (13.9, 25.1) 25.3 (19.3, 28.9) 21.5 (15.7, 26.9) 0.17 Zinc (µg/L) 787 (619, 932) 809 (637, 939) 784.5 (623.8, 934.4) 758.6 (593.7, 891.7) 0.33 Copper (µg/L) 951 (791, 1147) 936 (771, 1217) 970.2 (827.1, 1134.6) 951.4 (797.1, 1082.3) 0.56 Selenium (µg/L) 71.1 (50.5, 91.3) 72.4 (55.4, 93.3) 75.2 (50.5, 96.1) 62.9 (45.1, 84.2) 0.10 Age (10–14) Ferritin (ng/mL) 37.7 (27.8, 51.6) 39.4 (29.5, 60.3) 35.5 (26.9, 44.7) 40.7 (27.2, 59.5) 0.95 Folate (ng/mL) 4.7 (3.6, 6.1) 5.3 (4, 6.8) 4.5 (3.625, 5.7) 4 (3.6, 5.7) 0.08 Vitamin B12 (pg/mL) 209 (155, 310) 209.5 (157, 337) 213.5 (155.5, 302.5) 205.0 (154.0, 287.0) 0.56 Vitamin D (ng/mL) 24.1 (7.3) 22.9 (6.9) 24.1 (7.5) 25.0 (7.5) 0.33 Zinc (µg/L) 789.6 (605.6, 934.4) 773.2 (576.6, 900.7) 798.4 (631.2, 933.7) 789.6 (642.6, 949.4) 0.46 Copper (µg/L) 992 (824.6, 1146.8) 933.3 (765.7, 1188.6) 1014.1 (837.4, 1146.4) 987.7 (824.6, 1118.3) 0.78 Selenium (µg/L) 72 (48.4, 91.4) 73.4 (49.3, 102.5) 70.5 (46.3, 95.5) 68.5 (54.2, 86.2) 0.48 Age (15–18) Ferritin (ng/mL) 48.3 (23.5, 79.8) 66.1 (31.3, 105.4) 34.1 (17.5, 57.3) 35.2 (23.1, 56.5) 0.04 Folate (ng/mL) 4 (3.1, 6.3) 4 (2.85, 6.05) 4 (3, 6.2) 4.8 (3.6, 6.7) 0.20 Vitamin B12 (pg/mL) 244 (170, 400) 250.0 (174.5, 428.5) 250.0 (148.0, 443.0) 207.0 (175.0, 349.5) 0.59 Vitamin D (ng/mL) 17.3 (12, 25.1) 16.8 (12, 23.65) 24.4 (14.9, 30.4) 14.7 (11.35, 17.35) 0.91 Zinc (µg/L) 784.5 (621.4, 905.2) 838.3 (713.5, 969.1) 697.2 (623.8, 1011.0) 632.9 (539.5, 746.0) 0.004 Copper (µg/L) 926.1(731.2, 1107.3) 947.3 (773.6, 1235.0) 941.1 (761.1, 975.4) 817.1 (615.5, 991.4) 0.09 Selenium (µg/L) 70.6 (51.5, 89.5) 71.1 (55.6, 88.4) 85.9 (53.0, 100.2) 42.9 (37.7, 71.5) 0.08 Mean and range of T3 levels in each tertile were: Tertile 1 (mean = 2.0 µg/dL; range = 1.5–2.5 µg/dL) Tertile 2 (mean = 3.0 µg/dL; range = 2.6–3.5 µg/dL) and Tertile 3 (mean = 4.0 µg/dL, range of 3.6–4.5 µg/dL). Significant differences are indicated in bold. A P-trend value of < 0.05 indicates that the the observed trend is significant (increase or decrease of the micronutrient indicator across the T3 tertials) and was determined using the Jonckheere-Terpstra test. The association of serum micronutrient levels with serum T4 levels is shown in Table 3 . Vitamin D levels exhibit an increasing trend across T4 level tertiles 1–3. Vitamin D concentrations were higher in tertile 3 than tertiles 1 and 2, both in the combined age group and the older age group, but for the lower age group the tertile 3 levels were only higher than those of tertile 1. Vitamin D levels were also 1.3-fold higher in younger than older adolescents. An opposite trend was seen for zinc where levels were significantly (1.1-fold) higher for the younger age group in tertile 1 than in tertiles 2 and 3, and thus zinc levels display a clear negative correlation with T4 levels. In older adolescents (15–18 age group), selenium levels were significantly lower in tertile 1 compared to tertiles 2 and 3, and a positive correlation between selenium and T4 was apparent in this cohort. Table 3 Comparison of micronutrient status and serum T4 levels in adolescent Afghan refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to T4 levels. Characteristics T4 Overall T1 T2 T3 P-value Median (Q1, Q3) 4.7(3.74,5.7) 6.89(6.55,7.4) 9.05(8.52,10.45) All age groups Ferritin (ng/mL) 39 (27, 61.4) 39.1 (25.6, 62.6) 37.7 (27.0, 59.5) 39.4 (27.8, 57.3) 0.92 Folate (ng/mL) 4.4 (3.4, 6.1) 4.6 (3.6, 6.1) 4.6 (3.4, 6.3) 4.3 (3.3, 5.7) 0.41 Vitamin B12 (pg/mL) 219 (157, 348) 208.5 (159, 313) 244.0 (150.0, 350.0) 224.0 (158.0, 342.0) 0.65 Vitamin D (ng/mL) 22.3 (16.2, 27.5) 20.5 (15.0, 25.2) 21.1 (13.9, 27.7) 25.4 (20.0, 30.0) 0.003 Zinc (µg/L) 787.1 (618.6, 932.1) 805.5 (602.6, 1077.3) 806.1 (639.5, 933.1) 758.6 (593.7, 877.8) 0.16 Copper (µg/L) 951.5 (790.8, 1146.7) 928.5 (719.6, 1158.4) 970.2 (828.1, 1153.3) 956.3 (837.9, 1107.1) 0.65 Selenium (µg/L) 71.1 (50.5, 91.3) 69.4 (48.3, 95.7) 69.9 (51.5, 84.4) 73.7 (52.3, 95.0) 0.53 Age (10–14) 13.1 (12.4, 13.8) 13.1 (12.25, 13.85) 13.1 (12.3, 13.7) 13.1 (12.5, 13.7) Ferritin (ng/mL) 37.7 (27.8, 51.6) 35.8 (24.1, 51.4) 37.4 (29.4, 52.1) 39.4 (27.8, 54.7) 0.64 Folate (ng/mL) 4.7 (3.6, 6.1) 4.8 (3.6, 6.35) 4.8 (3.6, 5.95) 4.3 (3.6, 5.7) 0.66 Vitamin B12 (pg/mL) 209 (155, 310) 207.0 (155.5, 260.0) 259.0 (148.0, 316.0) 205.0 (156.0, 310.0) 0.68 Vitamin D (ng/mL) 24.1 (7.3) 22.0 (6.2) 24.5 (7.8) 25.8 (7.6) 0.02 Zinc (µg/L) 789.6 (605.6, 934.4) 884.0 (661.8, 1274.9) 798.4 (630.1, 941.3) 748.1 (593.7, 872.0) 0.03 Copper (µg/L) 992 (824.6, 1146.8) 971.6 (763.0, 1173.6) 999.5 (839.2, 1132.3) 974.6 (837.9, 1130.9) 0.96 Selenium (µg/L) 72 (48.4, 91.4) 78.9 (48.0, 109.7) 61.9 (45.4, 79.9) 72.5 (59.9, 87.5) 0.49 Age (15–18) Ferritin (ng/mL) 48.3 (23.5, 79.8) 60.7 (27.7, 92.2) 48.3 (18.06, 63.7) 44.3 (26.1, 82.6) 0.48 Folate (ng/mL) 4 (3.1, 6.3) 4.4 (3.3, 5.6) 4 (3.3, 6.6) 3.3 (2.6, 6.2) 0.29 Vitamin B12 (pg/mL) 244 (170, 400) 223.5 (178.5, 393.5) 227.0 (170.0, 400.0) 304.0 (170.0, 443.0) 0.75 Vitamin D (ng/mL) 17.3 (12, 25.1) 15.3 (12, 22.2) 13.5 (11.5, 24.5) 22.9 (17.3, 27.5) 0.05 Zinc (µg/L) 784.5 (621.4, 905.2) 724.7 (499.0, 838.3) 821.9 (657.1, 909.1) 783.8 (551.9, 941.0) 0.36 Copper (µg/L) 926.1 (731.2, 1107.3) 781.0 (630.7, 1081.0) 937.7 (814.6, 1217.0) 944.7 (731.2, 975.4) 0.46 Selenium (µg/L) 70.6 (51.5, 89.5) 58.2 (50.2, 71.1) 75.3 (60.6, 93.3) 84.9 (41.6, 111.1) 0.02 Vitamin D levels were also significantly associated with TSH levels in the younger age group (Table 4 ). Lower vitamin D levels were correlated with lower TSH levels, which is opposite to the trend observed between vitamin D and T4. Table 4 Comparison of micronutrient status and TSH levels in Afghan adolescent refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to TSH levels. Characteristics TSH Overall T1 T2 T3 P-value Median 1.18 (0.96,1.33) 1.7 (1.54, 1.87) 2.5 (2.28, 2.93) All age groups Ferritin (ng/mL) 39 (27, 61.4) 40.0 (28.0, 62.1) 44.0 (33.8, 67.8) 31.7 (20.7, 52.7) 0.14 Folate (ng/mL) 4.4 (3.4, 6.1) 4.6 (3.4, 6.65) 5 (3.6, 6.1) 4 (3.5, 5.2) 0.12 Vitamin B12 (pg/mL) 219 (157, 348) 220.5 (174, 352.5) 230.0 (165.0, 355.0) 209.0 (145.0, 305.0) 0.27 Vitamin D (ng/mL) 22.3 (16.2, 27.5) 22.2 (16.35, 28.6) 23.0 (14.8, 27.6) 21.5 (17.1, 26.2) 0.39 Zinc (µg/L) 787.1 (618.6, 932.1) 780.1 (631.2, 899.6) 748.1 (593.7, 877.8) 811.8 (644.4, 956.4) 0.42 Copper (µg/L) 951.5 (790.8, 1146.7) 1019.4 (814.0, 1221.3) 934.7 (761.1, 1077.9) 960.3 (828.1, 1132.9) 0.45 Selenium (µg/L) 71.1 (50.5, 91.3) 74.0 (52.5, 96.1) 67.5 (48.4, 86.2) 71.0 (49.9, 86.4) 0.47 Age (10–14) Ferritin (ng/mL) 37.7 (27.8, 51.6) 40.7 (28.8, 62.0) 40.7 (32.3, 51.2) 32.5 (21.7, 49.9) 0.08 Folate (ng/mL) 4.7 (3.6, 6.1) 4.8 (3.6, 6.6) 5.1 (4, 6.1) 4.1 (3.6, 5.2) 0.08 Vitamin B12 (pg/mL) 209 (155, 310) 209.0 (176.0, 292.0) 220.0 (157.0, 315.0) 207.0 (145.0, 305.0) 0.68 Vitamin D (ng/mL) 24.1 (19.3, 28.3) 26.8 (21.1,31.3) 24.7 (17.1,28.9) 22.4 (18.4, 26.9) 0.03 Zinc (µg/L) 789.6 (605.6, 934.4) 798.3 (642.6, 933.1) 724.9 (593.7, 884.0) 803.4 (600.1, 956.4) 0.77 Copper (µg/L) 992 (824.6, 1146.8) 1102.0 (821.5, 1200.8) 951.6 (837.9, 1118.3) 963.5 (824.6, 1132.9) 0.21 Selenium (µg/L) 72 (48.4, 91.4) 78.5 (64.0, 97.6) 63.2 (46.8, 86.9) 68.2 (47.9, 86.3) 0.07 Age (15–18) Ferritin (ng/mL) 48.3 (23.5, 79.8) 37.5 (18.1, 62.2) 63.6 (35.3, 88.1) 23.0 (11.6, 130.0) 0.55 Folate (ng/mL) 4 (3.1, 6.3) 4.5 (3.1, 6.8) 4.1 (2.6, 6.2) 3.8 (3.1, 4.6) 0.30 Vitamin B12 (pg/mL) 244 (170, 400) 254.0 (172.0, 395.0) 264.5 (179, 482) 210.0 (147.0, 350.0) 0.64 Vitamin D (ng/mL) 17.3 (12, 25.1) 16.3 (12, 23.2) 20.5 (12.6, 25.7) 13.4 (11.2, 19.2) 0.65 Zinc (µg/L) 784.5 (621.4, 905.2) 754.2 (618.6, 885.4) 793.6 (551.9, 876.0) 878.9 (697.2, 969.1) 0.33 Copper (µg/L) 926.1 (731.2, 1107.3) 937.7 (751.5, 1241.1) 804.3 (642.4, 975.4) 955.2 (851.8, 1156.0) 0.60 Selenium (µg/L) 70.6 (51.5, 89.5) 61.4 (45.1, 89.0) 71.7 (52.1, 85.9) 80.3 (69.9, 95.8) 0.15 Analysis of the relationship between serum micronutrients and thyroid hormone levels, on a continuous scale (Fig. 1 ), indicates that vitamin D exhibits a statistically significant positive correlation with T4 (r = 0.279) in the combined, younger (r = 0.277) and older (r = 0.319) age groups. In contrast, a statistically significant but negative correlation was observed when zinc levels were compared with T3 (r=-0.288) in the older age group and with T4 (r=-0.195) in the younger age group. Discussion To our knowledge, this is the first study evaluating the association between thyroid hormone levels and micronutrient status in Afghan adolescent refugees. Thyroid dysfunction is a worldwide public health problem, the etiology of which is mostly unknown. Clinically, thyroid dysfunctions mainly involve subclinical thyroid function disorder and is identified assessment of the levels of T3, T4 and TSH in serum along with other routine clinical investigations [ 25 ]. In humans, thyroid metabolism depends on processes which are influenced by micronutrients status [ 4 ]. Although, iodine is the key micronutrient in thyroid hormone biosynthesis [ 6 ], other micronutrients are also involved in maintaining normal thyroid function [ 23 ]. Thus, micronutrient deficiency can exacerbate thyroid disorders [ 26 ], which is concerning given that almost one third of the global population suffer for deficiency in one or more micronutrients. Our study indicates that there are age and gender dependent differences in thyroid hormone levels among adolescent Afghan refugees. Specifically, T3 and TSH were significantly higher in younger (10–14 years) than older adolescents (15–18 years) while T4 levels were significantly higher in boys compared to girls. These observed age-related changes in thyroid hormone levels align with findings from previous studies, such as those conducted on Danish (aged 6–18 years) and Indian (aged 6–17 years) cohort of school age children,, where the median values of free T3 and T4 decreased with increasing age [ 27 , 28 ]. However, our cohort is distinct in being composed solely of refugees, a population that may experience unique environmental and nutritional challenges exacerbating these age-related changes. The age-related changes were more obvious in young children with convergence to adult like ranges after age 15 years and above. Similarly, higher levels of thyroid hormones in boys than girls, as found in our study, has also been reported previously [ 29 ]. It is important to note that these differences could be influenced by factors not fully explored in this study, such as variations in physical activity, diet, and exposure to environmental stressors like chronic malnutrition or psychosocial stress, which are prevalent in refugee populations. However, it should be noted that the age and gender-based changes in thyroid hormones levels may also be influenced by other factors, such as ethnicity, body mass index and methodological approaches to measure thyroid parameters [ 30 ]. These variables are important for understanding the full spectrum of influences on thyroid function and should be considered when interpreting findings especially in a diverse and vulnerable population such as refugees. The current study reports an association between selected micronutrients and thyroid function, as reported previously. For example, a positive association was observed between vitamin D and both TSH and T4 levels in younger adolescents aged 10–14 years. These findings are in concordance with previous studies reporting significantly low levels of TSH and T4 in vitamin D deficient individuals aged 12 to 18 years [ 31 ] and older than 18 years [ 32 ]. Vitamin D deficiency had been implicated in autoimmune thyroid disorders including Hashimoto’s thyroiditis and Graves`s disease [ 33 ]. Although, the exact mechanism by which vitamin D deficiency impairs thyroid functions is unknown, experimental evidence on mice model suggests that vitamin D exert its effect by increasing the mRNA expression of de-iodinase 2 gene, an enzyme necessary for conversion of T4 to T3 [ 34 ]. Other possible mechanisms include suppression of TSH-stimulated adenylyl cyclase activity and enhanced iodine uptake [ 35 ]. Several clinical trials have investigated the impact of vitamin D supplementation on thyroid function [ 36 – 38 ]. Majority research reported a significant reduction in anti-thyroid antibodies following vitamin D supplementation with little or no effect on thyroid hormones levels [ 33 ]. However, a larger clinical trial encompassing 11,017 participants mean aged 48 ± 16 (18–95 years) with 58% females, receiving vitamin D supplementation for 12 months reported both decrease in serum TSH, anti-TPO, anti-TG and TG levels over time and increase in serum FT3 and FT4 leading to reduction in hypothyroidism and thyroid autoimmune disorder [ 39 ]. Among the trace elements, zinc exhibited a significant negative correlation with serum T3 and T4 and a positive, but non-significant, correlation with serum TSH levels. While this observation aligns with the findings of [ 40 ], it is important to note that other studies, such as those by [ 41 , 42 ] reported either no correlation or a positive correlation between zinc levels and thyroid hormones. These differences in findings highlight the need for further investigation into the specific mechanisms through which zinc interacts with thyroid hormones. Unlike the consistent role observed in other trace elements, zinc's influence on thyroid function appears to be complex and potentially context dependent. Zinc helps in thyroid metabolism through synthesis of the thyrotropin-releasing hormone (TRH) in the hypothalamus, as cofactor for deiodinase I and II enzyme that help in conversion of T4 to T3 or as structural component of T3 receptor [ 21 , 43 , 44 ]. Additionally, our study showed a positive association between T4 status and selenium levels. Selenium is a critical component of the deiodinase enzymes, which are responsible for the conversion of thyroxine (T4) into the more active triiodothyronine (T3) [ 45 ]. It exerts its effects on thyroid metabolism seleno-proteins, a group of biologically active protein molecules involved in diverse process including DNA synthesis and thyroid metabolism [ 14 ]. Research described the importance of adequate selenium levels for optimal thyroid function, highlighting how selenium deficiency can impair the conversion process, potentially leading to altered thyroid hormone levels and subsequent metabolic disturbances [ 46 ]. Moreover clinical research suggest that selenium deficiency is linked with a higher risk of elevated anti-thyroid antibody levels, while selenium supplementation has been shown to reduce thyroid peroxidase antibody levels [ 47 – 49 ]. Selenium status has also been correlated with Grave’s disease [ 50 ], autoimmune hypothyroidism and thyroid cancer [ 51 ]. In the context of adolescent Afghan refugees, who are likely exposed to a variety of environmental stressors and nutritional deficiencies, our findings of a positive association between T4 status and selenium levels suggest that selenium may play a crucial role in maintaining thyroid function amidst these challenges. Although, our study is the first of its kind assessing the association between micronutrients status and thyroid function in vulnerable refugee population, it has some limitations. First, due to limited sample size and cross-sectional design, the study findings cannot be generalized to other refugee and host population. Secondly, we could not collect dietary data and other lifestyle factors which may also be associated with micronutrients status and thyroid profile in these population. None the less, the study provides important baseline data information regarding the potential impact of micronutrients on thyroid profile in a vulnerable population. Conclusion Overall, our study reports age and gender-based impact of different micronutrients (both vitamins and minerals) on thyroid function in adolescent Afghan refugees. Of these, vitamin D and zinc are especially important as the serum level of these micronutrients is significantly correlated with thyroid hormone levels in this population. These findings highlight the importance of close monitoring and effective nutritional interventions to prevent thyroid related disorders in vulnerable population such as refugees. Declarations Ethics approval and consent to participate The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Board of the Khyber Medical University Pakistan vide letter number DIR/KMU-EB/PR/000766 dated 3 February 2020. Before recruitment, a written informed consent was obtained from all the participants and their parents. Consent for publication Not applicable Competing interests The authors declare no competing interests Funding This research was funded by a Seed Fund grant from the School of Biological Sciences (University of Reading) and supported by a BBSRC-DRINC grant (BB/N021800/1) to SCA. M.S. is recipient of Faculty Grant from Office of Research, Innovation and Commercialization (ORIC), Khyber Medical University. Author Contribution S.S performed the experimental work, data analysis, drafted and edited the manuscript. M.S; N.S and S.C.A. were involved in supervising the research and editing the manuscript. K.I; M.S.K and H.A.A in data collection, analysis and writing and revision of the manuscript. All authors read and approved the final manuscript. Acknowledgement The authors would like to thank Commissionerate Afghan Refugees Khyber Pakhtunkhwa for facilitating data collection and ground support. 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Babić Leko M, Jureško I, Rozić I, Pleić N, Gunjača I, Zemunik T. Vitamin D and the Thyroid: A Critical Review of the Current Evidence. Int J Mol Sci. 2023;24(4):3586. Alrefaie Z, Awad H. Effect of vitamin D3 on thyroid function and de-iodinase 2 expression in diabetic rats. Arch Physiol Biochem. 2015;121(5):206–9. Berg JP, Liane KM, Bjørhovde SB, Bjøro T, Torjesen PA, Haug E. Vitamin D receptor binding and biological effects of cholecalciferol analogues in rat thyroid cells. J Steroid Biochem Mol Biol. 1994;50(3–4):145–50. Aswathy SH, Narendrakumar U, Manjubala I. Commercial hydrogels for biomedical applications. Heliyon. 2020;6(4):e03719. Grove-Laugesen D, Malmstroem S, Ebbehoj E, Riis AL, Watt T, Hansen KW, et al. Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves’ disease: a randomized clinical trial. Endocrine. 2019;66:386–97. Jiang H, Chen X, Qian X, Shao S. 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Baltaci AK, Mogulkoc R, Belviranli M. L-thyroxine-induced hyperthyroidism affects elements and zinc in rats. Bratisl Lek Listy. 2013;114(3):125–8. Civitareale D, Saiardi A, Falasca P. Purification and characterization of thyroid transcription factor 2. Biochem J. 1994;304(Pt 3):981–5. (Pt 3)(. Sabatino L, Vassalle C, Del Seppia C, Iervasi G. Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions. Endocrinol Metab (Seoul). 2021;36(5):952–64. Ventura M, Melo M, Carrilho F. Selenium and Thyroid Disease: From Pathophysiology to Treatment. Int J Endocrinol. 2017;2017:1297658. Mantovani G, Isidori AM, Moretti C, Di Dato C, Greco E, Ciolli P, et al. Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the SERENA study, a randomized, double-blind, placebo-controlled trial. Endocrine. 2019;66(3):542–50. Rostami R, Nourooz-Zadeh S, Mohammadi A, Khalkhali HR, Ferns G, Nourooz-Zadeh J. 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Supplementary Files SupplementaryTable1.docx Cite Share Download PDF Status: Published Journal Publication published 03 Jun, 2025 Read the published version in Thyroid Research → Version 1 posted Editorial decision: Revision requested 10 Nov, 2024 Reviews received at journal 10 Nov, 2024 Reviewers agreed at journal 05 Nov, 2024 Reviewers agreed at journal 03 Nov, 2024 Reviews received at journal 03 Nov, 2024 Reviewers agreed at journal 03 Nov, 2024 Reviewers invited by journal 03 Nov, 2024 Editor assigned by journal 31 Oct, 2024 Submission checks completed at journal 31 Oct, 2024 First submitted to journal 28 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5349851","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":376226730,"identity":"2541fd7c-2065-4658-80c5-ff45768fd00e","order_by":0,"name":"Saima Shaheen","email":"","orcid":"","institution":"Khyber Girls Medical College","correspondingAuthor":false,"prefix":"","firstName":"Saima","middleName":"","lastName":"Shaheen","suffix":""},{"id":376226731,"identity":"db45900b-8aa5-4664-9223-3de3c861295e","order_by":1,"name":"Muhammad Shahzad","email":"","orcid":"","institution":"Zarqa University","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Shahzad","suffix":""},{"id":376226732,"identity":"9ace3994-5061-4cac-8835-12997fac9cd5","order_by":2,"name":"Nabila Sher","email":"","orcid":"","institution":"Khyber Girls Medical College","correspondingAuthor":false,"prefix":"","firstName":"Nabila","middleName":"","lastName":"Sher","suffix":""},{"id":376226733,"identity":"9e1ddf27-67bd-4d81-a669-c376310251c9","order_by":3,"name":"Muhammad Shabbir Khan","email":"","orcid":"","institution":"Khyber Medical College","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Shabbir","lastName":"Khan","suffix":""},{"id":376226734,"identity":"a0e801eb-8ac8-443a-9156-aedeafec6925","order_by":4,"name":"Khalid Iqbal","email":"","orcid":"","institution":"Khyber Medical University","correspondingAuthor":false,"prefix":"","firstName":"Khalid","middleName":"","lastName":"Iqbal","suffix":""},{"id":376226735,"identity":"7b6938d3-b6b0-4126-8f3b-8b85b721c33e","order_by":5,"name":"Habab Ali Ahmad","email":"","orcid":"","institution":"Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology","correspondingAuthor":false,"prefix":"","firstName":"Habab","middleName":"Ali","lastName":"Ahmad","suffix":""},{"id":376226736,"identity":"028140b7-0295-4e57-8895-4781f342d34b","order_by":6,"name":"Simon C Andrews","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCklEQVRIiWNgGAWjYPACZhDB+ABEtMHEJIjQwmxAshY2kCLGBkJa5BuYHzD83GGdzy+R/qy6osJOtk+6/QLDjxqGxJkN2LUYHGAzYOw9k245c0aO2c0zZ5KN22TOFDD2HGNInI3DFgMGHgYG3rbDBga3c9huNrYxJ7ZJ5CQw8DYwJM7D6TAeBsa/QC32t9OfFTb+qwdrYfyLRwvDAR4GZrAt0glmjI0Nh4Fa0g8wg2zB6bDDbAaHZdvSDSTuvzGWbDh23BhoC8NhmWMSxri8L9/e/PDh2zZrA/6e4w8/NtRUy86fkf7w4ZsaG9kZB3BYA4wRdCkegwMEIxINsD8gSfkoGAWjYBQMewAA8gtXFYQBiFYAAAAASUVORK5CYII=","orcid":"","institution":"University of Reading","correspondingAuthor":true,"prefix":"","firstName":"Simon","middleName":"C","lastName":"Andrews","suffix":""}],"badges":[],"createdAt":"2024-10-28 22:23:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5349851/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5349851/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13044-025-00239-6","type":"published","date":"2025-06-03T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":68798693,"identity":"cae1ad6d-a3ea-4920-8dd7-b20a32f83af8","added_by":"auto","created_at":"2024-11-12 06:56:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53000,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution (center), scatter plot (lower triangle) and correlation (upper triangle) of the micronutrients with T3, T4 and TSH by gender (all genders)\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5349851/v1/d8ac110d6153dec0c59c38cb.png"},{"id":84242367,"identity":"4b9e16c3-6d9a-435f-952a-cb2ddb0891d4","added_by":"auto","created_at":"2025-06-09 16:06:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1171507,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5349851/v1/796a74d1-8d09-48fa-9757-b76931f71bf1.pdf"},{"id":68798694,"identity":"4f02efd3-ea5f-415f-a683-413645c784ea","added_by":"auto","created_at":"2024-11-12 06:56:57","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19245,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5349851/v1/6b927f9297c4fad740813313.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of micronutrient status on thyroid function in adolescent Afghan refugees; a cross-sectional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMicronutrient deficiencies are generally caused by inadequate intake of essential micronutrients (vitamins and minerals) and represent a major global public health burden. This problem is largely limited to developing nations and socioeconomically disadvantaged populations. Estimated reports from the World Health Organization (WHO) indicate that over 2\u0026nbsp;billion people worldwide suffer the physiological consequences of micronutrient insufficiency [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Micronutrient insufficiencies are widespread causes of suppressed immune function, disturbed metabolism, impaired physical and cognitive development in children, and increased risk of chronic conditions such as cancer and cardiovascular diseases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Optimal metabolism in humans is predicated on adequate supplies of micronutrients that act as enzyme cofactors and structural components for macromolecules. One of the major human-health impacts of micronutrient availability is thyroid metabolism and function [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn humans, the thyroid gland plays an important role in growth and development through maintenance of homeostasis and supporting the normal function of the cardiovascular, reproductive and nervous systems [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Thyroid function is primarily regulated by the hypothalamic-pituitary-thyroid axis through the action of thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine [T4]. Thyroid hormones are crucial for cellular development, differentiation, growth, and regulation of protein, lipid and carbohydrate metabolism in nearly all tissues [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Thyroid hormone signaling is also essential for normal growth and maturation of organs such as the brain, lung, heart, skeletal muscle and bone. However, the production of inappropriate amounts of thyroid hormones results in hypothyroidism or hyperthyroidism which have devastating consequences on human health. Hyperthyroidism causes weight loss, heat intolerance and rapid heartbeat (tachycardia) while hypothyroidism is characterized by weight gain, feeling cold (cold intolerance), constipation, enlargement of the thyroid gland (goiter) and slowed metabolism (metabolic disruptions) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although the exact etiology and pathogenesis of thyroid disorders is not known, a role for micronutrients and trace elements is frequently suggested [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Several micronutrients, especially trace elements, are found in higher concentration in the thyroid gland than in any other tissue in the body [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and are essential for thyroid hormone synthesis, metabolism and function. Micronutrient status is also a key determinant of risk and severity of autoimmune thyroid disorders (AITD) as both micronutrient deficiency and excess can promote autoimmune attack on the thyroid gland. Indeed, epidemiological studies indicate an increased susceptibility to pathogenic thyroid dysfunction is linked to the dietary availability of the micronutrients iodine, iron, selenium, copper, zinc, and vitamins B12 and D [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSelenium (Se) is a constituent of three iodothyronine deiodinase enzymes that catalyze the conversion of prohormone thyroxine (T4) to the active hormone 3,3\u0026prime;,5-triiodothyronine (T3). Thus, Se plays a direct role in the metabolism and activation of thyroid hormones ([\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Se deficiency has been repeatedly associated with increased risk of AITD, such as Graves\u0026rsquo; disease and Hashimotos\u0026rsquo;s thyroiditis, and is also linked with exacerbated developmental hypothyroidism primarily caused by iodine deficiency [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Zinc is another essential micronutrient with a well-established role in thyroid hormone biosynthesis, metabolism and signaling. Zn is an essential structural component and catalytic cofactor for numerous enzymes involved in thyroid hormone biosynthesis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], playing a role in thyrotropin-releasing hormone (TRH) production. TRH stimulates release of thyroid stimulating hormone (TSH) from the pituitary, which in turn acts on the thyroid to promote thyroid hormone production [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. \u003cem\u003eIn-vivo\u003c/em\u003e studies in animal models demonstrate that inadequate zinc levels impair thyroid hormone production, potentially causing hypothyroidism, developmental abnormalities and compromised immunity [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thyroid hormones are also reported to modulate Zn homeostasis by regulating its intestinal absorption and renal reabsorption in rats [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In humans, the finding of a strong correlation between tissue levels of thyroid hormones and zinc suggests an intimate bidirectional relationship between the two [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Furthermore, zinc supplementation in humans results in a significant increase in plasma TSH, T3 and T4 levels [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough, the impact of micronutrients on thyroid functions has been frequently reported in the literature, such studies have been mostly focused on thyroid disease patients, children, and pregnant women [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Until now, little or no research investigating the relationship between micronutrient status and thyroid function has been conducted in populations that are at high risk of malnutrition, such as refugees. Therefore, this cross-sectional study aimed to investigate the associations between thyroid hormone levels and micronutrient status in a cohort of adolescents Afghan refugees residing in a refugee camp in Pakistan.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and population\u003c/h2\u003e \u003cp\u003eThis cross-sectional study analysed 206 adolescent (both male and female) Afghan refugees (aged 10\u0026ndash;19 years) residing in Khazana refugee camp, the largest refugee camp (5000 residents) in Peshawar, Pakistan. They were recruited by a non-probability, consecutive sampling method in a study assessing the nutritional status of apparently healthy adolescents [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Participants with missing variables in the questionnaire data (n\u0026thinsp;=\u0026thinsp;2) or plasma micronutrients data (n\u0026thinsp;=\u0026thinsp;17) or thyroid hormones (n\u0026thinsp;=\u0026thinsp;16) were excluded from analysis. A final sample of 182 participants (91 boys and 91 girls) were included in the analysis. An information sheet containing the detailed procedures and purpose of the study in an easy to understand, local language (Pashto and Dari) was provided to all the participants before signing a written informed consent. Ethical and administrative approval for the study was provided by Khyber Medical University and the Peshawar Afghan Commissionerate (Peshawar), respectively.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData and samples collection\u003c/h3\u003e\n\u003cp\u003eParticipant demographic and socioeconomic status information was collected by an interviewer administered, structured questionnaire. Trained data collectors measured the height and weight of the participants using standard procedures. The body mass index (kg/m\u003csup\u003e2\u003c/sup\u003e) was calculated using the participants\u0026rsquo; height and weight. Blood samples were collected from the participants between 08:00\u0026ndash;10:00 am. Plasma and serum were separated, transported to the main lab within 4 hours and stored at -80\u0026deg;C prior to analysis.\u003c/p\u003e\n\u003ch3\u003eLaboratory assays\u003c/h3\u003e\n\u003cp\u003eComplete blood counts were performed on freshly collected whole blood samples using a Sysmex automatic haematology analyzer (XP-100, Jalan Tukang, Singapore). Vitamin D status was assessed using a 25-OH vitamin D Diasorin radioimmunoassay ELISA kit (Euroimmun, Germany) while ferritin, vitamin B12 and folate were assessed using the Abbott Architect i2000 analyser (Abbott Diagnostics, Zug, Switzerland). Thyroid function tests were performed to measure the serum levels of total T3, T4 and thyroid stimulating hormone (TSH) using an Elecsys electrochemiluminescence based assay on a Cobas e 411 analyser (Roche Diagnostics, Germany). The levels of iron, zinc, selenium and copper were determined by reconstituting freeze-dried plasma samples in Milli-Q (18 MΩ) water and subjecting it to inductively coupled plasma mass spectrometry analysis (ICP-MS; Thermo Fisher Scientific iCAPQ, Bremen, Germany).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAge is reported as mean (SD) and age categories, educational status, family size and female household head educational status are reported as frequencies (percentage). Thyroid hormone (T3, T4 and TSH) data were categorized into tertiles. Micronutrient concentrations are described as medians (Q1 and Q3) by tertiles for T3, T4 and TSH. Quantile regression was used to investigate association among thyroid hormones (T3, T4 and TSH) and basic characteristics (age, gender and BMI). Due to non-normal distribution of the micronutrient levels, the linear trends of these biomarkers across ordered categories of thyroid hormones (T3, T4 and TSH) were assessed using the Jonckheere Terpstra Test. Correlation between biomarkers and thyroid hormones were assessed using Spearman rank correlation. All data analysis was conducted using SAS Version 9.4.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics of the study participants\u003c/h2\u003e \u003cp\u003eGeneral characteristics of the 206 study participants, 103 males and 103 females are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Participants were divided into two age groups, 10\u0026ndash;14 (63.7%) and 15\u0026ndash;19 (36.3%) years. Background characteristics of the study participants were described previously and are thus provided here in supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of thyroid hormone levels with age, sex and BMI\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll ages\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (Categories)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.22 (0.05, 0.43) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2 (-0.75, 0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.46 (0.01, 0.74) *\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Gender\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.12 (-0.01, 0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.29 (0.64, 1.94) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07 (-0.27, 0.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.001 (-0.04, 0.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1 (-0.08, 0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04 (-0.03, 0.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge Group (10\u0026ndash;14 Years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Gender\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18 (0, 0.29) **\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.32 (0.36, 2.04) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.11 (-0.47, 0.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.02 (-0.04, 0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17 (-0.06, 0.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08 (-0.04, 0.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge Group (14\u0026ndash;19 Years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Gender\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.16 (-0.33, 0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.26 (0.15, 2.21) *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.29 (-0.05, 0.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.01 (-0.07, 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001 (-0.18, 0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.01 (-0.09, 0.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eCoefficient estimates with 95% CI from quantile regression modeling median of T3, T4 and TSH to investigate association with age, sex and BMI. * p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **p-value\u0026thinsp;=\u0026thinsp;0.05\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAssociation between demographic and nutritional status, and thyroid function biomarkers\u003c/h3\u003e\n\u003cp\u003eWe first assessed whether there is any relationship between demographic characteristics (age, gender), nutritional status (BMI) and median levels of thyroid hormones among the participants (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Overall, the results show that median levels of T3 and TSH are significantly higher in 10\u0026ndash;14 years as compared to 15\u0026ndash;18 years. Although, no significant association was observed for median levels of T4 with age, its concentration was significantly higher in boys compared to girls. Stratified analysis by age groups showed that T4 levels are significantly higher among boys in both age groups while T3 was high only younger adolescent group (10\u0026ndash;14 years). However, no significant association was observed between thyroid hormones level and BMI (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eAssociation between plasma micronutrients levels and thyroid function biomarkers\u003c/h3\u003e\n\u003cp\u003eTo assess the association of selected micronutrients with thyroid function biomarkers, the median concentration of the micronutrients was divided into three equivalently sized tertiles based on serum T3, T4 and TSH levels. No statistically significant trend was observed between serum micronutrient levels across the three tertiles based on serum T3 levels (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, stratified analysis by age showed a significantly decreasing trend in serum ferritin and zinc levels from across tertile 1 \u0026ndash;\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of micronutrientstatus and T3 levels in adolescent Afghan refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to T3 levels.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eTertile 1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eTertile 2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eTertile 3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eP-trend\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1, Q3) of T3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.05 (0.93, 1.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.42 (1.33, 1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.79 (1.67, 2.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll age groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (27, 61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.0 (29.5, 79.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.0 (24.6, 49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.6 (26.54, 59.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4 (3.4, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6 (3.1, 6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.3 (3.6, 5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.2 (3.6, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219 (157, 348)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e228 (167, 392)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e220.0 (155.0, 349.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e205.0 (161.0, 300.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.3 (16.2, 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.4 (13.9, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.3 (19.3, 28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.5 (15.7, 26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e787 (619, 932)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e809 (637, 939)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e784.5 (623.8, 934.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e758.6 (593.7, 891.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e951 (791, 1147)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e936 (771, 1217)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e970.2 (827.1, 1134.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e951.4 (797.1, 1082.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.1 (50.5, 91.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.4 (55.4, 93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.2 (50.5, 96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.9 (45.1, 84.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (10\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.7 (27.8, 51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.4 (29.5, 60.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.5 (26.9, 44.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.7 (27.2, 59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (3.6, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.3 (4, 6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.5 (3.625, 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.6, 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e209 (155, 310)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209.5 (157, 337)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e213.5 (155.5, 302.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e205.0 (154.0, 287.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.1 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.9 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.1 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.0 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e789.6 (605.6, 934.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e773.2 (576.6, 900.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e798.4 (631.2, 933.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e789.6 (642.6, 949.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e992 (824.6, 1146.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e933.3 (765.7, 1188.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1014.1 (837.4, 1146.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e987.7 (824.6, 1118.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (48.4, 91.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.4 (49.3, 102.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.5 (46.3, 95.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.5 (54.2, 86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (15\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.3 (23.5, 79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.1 (31.3, 105.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.1 (17.5, 57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.2 (23.1, 56.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.1, 6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.85, 6.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3, 6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.8 (3.6, 6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (170, 400)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250.0 (174.5, 428.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e250.0 (148.0, 443.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e207.0 (175.0, 349.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.3 (12, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.8 (12, 23.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.4 (14.9, 30.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7 (11.35, 17.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e784.5 (621.4, 905.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e838.3 (713.5, 969.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e697.2 (623.8, 1011.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e632.9 (539.5, 746.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926.1(731.2, 1107.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e947.3 (773.6, 1235.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e941.1 (761.1, 975.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e817.1 (615.5, 991.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.6 (51.5, 89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.1 (55.6, 88.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.9 (53.0, 100.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.9 (37.7, 71.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eMean and range of T3 levels in each tertile were: Tertile 1 (mean\u0026thinsp;=\u0026thinsp;2.0 \u0026micro;g/dL; range\u0026thinsp;=\u0026thinsp;1.5\u0026ndash;2.5 \u0026micro;g/dL) Tertile 2 (mean\u0026thinsp;=\u0026thinsp;3.0 \u0026micro;g/dL; range\u0026thinsp;=\u0026thinsp;2.6\u0026ndash;3.5 \u0026micro;g/dL) and Tertile 3 (mean\u0026thinsp;=\u0026thinsp;4.0 \u0026micro;g/dL, range\u003c/em\u003e of \u003cem\u003e3.6\u0026ndash;4.5 \u0026micro;g/dL). Significant differences are indicated in bold. A P-trend value of \u0026lt;\u0026thinsp;0.05 indicates that the the observed trend is significant (increase or decrease of the micronutrient indicator across the T3 tertials) and was determined using the Jonckheere-Terpstra test.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe association of serum micronutrient levels with serum T4 levels is shown in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Vitamin D levels exhibit an increasing trend across T4 level tertiles 1\u0026ndash;3. Vitamin D concentrations were higher in tertile 3 than tertiles 1 and 2, both in the combined age group and the older age group, but for the lower age group the tertile 3 levels were only higher than those of tertile 1. Vitamin D levels were also 1.3-fold higher in younger than older adolescents. An opposite trend was seen for zinc where levels were significantly (1.1-fold) higher for the younger age group in tertile 1 than in tertiles 2 and 3, and thus zinc levels display a clear negative correlation with T4 levels. In older adolescents (15\u0026ndash;18 age group), selenium levels were significantly lower in tertile 1 compared to tertiles 2 and 3, and a positive correlation between selenium and T4 was apparent in this cohort.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of micronutrient status and serum T4 levels in adolescent Afghan refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to T4 levels.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eP-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Q1, Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7(3.74,5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.89(6.55,7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.05(8.52,10.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll age groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (27, 61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.1 (25.6, 62.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.7 (27.0, 59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.4 (27.8, 57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4 (3.4, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6 (3.6, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.6 (3.4, 6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.3 (3.3, 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219 (157, 348)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e208.5 (159, 313)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e244.0 (150.0, 350.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e224.0 (158.0, 342.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.3 (16.2, 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.5 (15.0, 25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.1 (13.9, 27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.4 (20.0, 30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e787.1 (618.6, 932.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e805.5 (602.6, 1077.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e806.1 (639.5, 933.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e758.6 (593.7, 877.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e951.5 (790.8, 1146.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e928.5 (719.6, 1158.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e970.2 (828.1, 1153.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e956.3 (837.9, 1107.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.1 (50.5, 91.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.4 (48.3, 95.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.9 (51.5, 84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.7 (52.3, 95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (10\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.1 (12.4, 13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.1 (12.25, 13.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.1 (12.3, 13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.1 (12.5, 13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.7 (27.8, 51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.8 (24.1, 51.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.4 (29.4, 52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.4 (27.8, 54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (3.6, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8 (3.6, 6.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.8 (3.6, 5.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.3 (3.6, 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e209 (155, 310)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e207.0 (155.5, 260.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e259.0 (148.0, 316.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e205.0 (156.0, 310.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.1 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.0 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.5 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.8 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e789.6 (605.6, 934.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e884.0 (661.8, 1274.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e798.4 (630.1, 941.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e748.1 (593.7, 872.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e992 (824.6, 1146.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e971.6 (763.0, 1173.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e999.5 (839.2, 1132.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e974.6 (837.9, 1130.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (48.4, 91.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.9 (48.0, 109.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.9 (45.4, 79.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.5 (59.9, 87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (15\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.3 (23.5, 79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.7 (27.7, 92.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.3 (18.06, 63.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44.3 (26.1, 82.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.1, 6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.4 (3.3, 5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (3.3, 6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3 (2.6, 6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (170, 400)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e223.5 (178.5, 393.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e227.0 (170.0, 400.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e304.0 (170.0, 443.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.3 (12, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.3 (12, 22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.5 (11.5, 24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.9 (17.3, 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e784.5 (621.4, 905.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e724.7 (499.0, 838.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e821.9 (657.1, 909.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e783.8 (551.9, 941.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926.1 (731.2, 1107.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e781.0 (630.7, 1081.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e937.7 (814.6, 1217.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e944.7 (731.2, 975.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.6 (51.5, 89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.2 (50.2, 71.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.3 (60.6, 93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.9 (41.6, 111.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVitamin D levels were also significantly associated with TSH levels in the younger age group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Lower vitamin D levels were correlated with lower TSH levels, which is opposite to the trend observed between vitamin D and T4.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of micronutrient status and TSH levels in Afghan adolescent refugees. Comparison was achieved by dividing participants into three equally-sized tertiles according to TSH levels.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOverall\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eP-value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.18 (0.96,1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.7 (1.54, 1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.5 (2.28, 2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll age groups\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (27, 61.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.0 (28.0, 62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.0 (33.8, 67.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.7 (20.7, 52.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4 (3.4, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6 (3.4, 6.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3.6, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (3.5, 5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219 (157, 348)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e220.5 (174, 352.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e230.0 (165.0, 355.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e209.0 (145.0, 305.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.3 (16.2, 27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.2 (16.35, 28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.0 (14.8, 27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.5 (17.1, 26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e787.1 (618.6, 932.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e780.1 (631.2, 899.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e748.1 (593.7, 877.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e811.8 (644.4, 956.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e951.5 (790.8, 1146.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1019.4 (814.0, 1221.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e934.7 (761.1, 1077.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e960.3 (828.1, 1132.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.1 (50.5, 91.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.0 (52.5, 96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.5 (48.4, 86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.0 (49.9, 86.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (10\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.7 (27.8, 51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.7 (28.8, 62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.7 (32.3, 51.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.5 (21.7, 49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.7 (3.6, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8 (3.6, 6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.1 (4, 6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.1 (3.6, 5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e209 (155, 310)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209.0 (176.0, 292.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e220.0 (157.0, 315.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e207.0 (145.0, 305.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.1 (19.3, 28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.8 (21.1,31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.7 (17.1,28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.4 (18.4, 26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e789.6 (605.6, 934.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e798.3 (642.6, 933.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e724.9 (593.7, 884.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e803.4 (600.1, 956.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e992 (824.6, 1146.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1102.0 (821.5, 1200.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e951.6 (837.9, 1118.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e963.5 (824.6, 1132.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (48.4, 91.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.5 (64.0, 97.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.2 (46.8, 86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.2 (47.9, 86.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (15\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.3 (23.5, 79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5 (18.1, 62.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.6 (35.3, 88.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.0 (11.6, 130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolate (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3.1, 6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5 (3.1, 6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.1 (2.6, 6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.8 (3.1, 4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin B12 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (170, 400)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e254.0 (172.0, 395.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e264.5 (179, 482)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e210.0 (147.0, 350.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.3 (12, 25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.3 (12, 23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.5 (12.6, 25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.4 (11.2, 19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e784.5 (621.4, 905.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e754.2 (618.6, 885.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e793.6 (551.9, 876.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e878.9 (697.2, 969.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopper (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926.1 (731.2, 1107.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e937.7 (751.5, 1241.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e804.3 (642.4, 975.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e955.2 (851.8, 1156.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.6 (51.5, 89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.4 (45.1, 89.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.7 (52.1, 85.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.3 (69.9, 95.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAnalysis of the relationship between serum micronutrients and thyroid hormone levels, on a continuous scale (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), indicates that vitamin D exhibits a statistically significant positive correlation with T4 (r\u0026thinsp;=\u0026thinsp;0.279) in the combined, younger (r\u0026thinsp;=\u0026thinsp;0.277) and older (r\u0026thinsp;=\u0026thinsp;0.319) age groups. In contrast, a statistically significant but negative correlation was observed when zinc levels were compared with T3 (r=-0.288) in the older age group and with T4 (r=-0.195) in the younger age group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study evaluating the association between thyroid hormone levels and micronutrient status in Afghan adolescent refugees. Thyroid dysfunction is a worldwide public health problem, the etiology of which is mostly unknown. Clinically, thyroid dysfunctions mainly involve subclinical thyroid function disorder and is identified assessment of the levels of T3, T4 and TSH in serum along with other routine clinical investigations [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In humans, thyroid metabolism depends on processes which are influenced by micronutrients status [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although, iodine is the key micronutrient in thyroid hormone biosynthesis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], other micronutrients are also involved in maintaining normal thyroid function [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Thus, micronutrient deficiency can exacerbate thyroid disorders [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], which is concerning given that almost one third of the global population suffer for deficiency in one or more micronutrients.\u003c/p\u003e \u003cp\u003eOur study indicates that there are age and gender dependent differences in thyroid hormone levels among adolescent Afghan refugees. Specifically, T3 and TSH were significantly higher in younger (10\u0026ndash;14 years) than older adolescents (15\u0026ndash;18 years) while T4 levels were significantly higher in boys compared to girls. These observed age-related changes in thyroid hormone levels align with findings from previous studies, such as those conducted on Danish (aged 6\u0026ndash;18 years) and Indian (aged 6\u0026ndash;17 years) cohort of school age children,, where the median values of free T3 and T4 decreased with increasing age [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, our cohort is distinct in being composed solely of refugees, a population that may experience unique environmental and nutritional challenges exacerbating these age-related changes. The age-related changes were more obvious in young children with convergence to adult like ranges after age 15 years and above. Similarly, higher levels of thyroid hormones in boys than girls, as found in our study, has also been reported previously [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. It is important to note that these differences could be influenced by factors not fully explored in this study, such as variations in physical activity, diet, and exposure to environmental stressors like chronic malnutrition or psychosocial stress, which are prevalent in refugee populations. However, it should be noted that the age and gender-based changes in thyroid hormones levels may also be influenced by other factors, such as ethnicity, body mass index and methodological approaches to measure thyroid parameters [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. These variables are important for understanding the full spectrum of influences on thyroid function and should be considered when interpreting findings especially in a diverse and vulnerable population such as refugees.\u003c/p\u003e \u003cp\u003eThe current study reports an association between selected micronutrients and thyroid function, as reported previously. For example, a positive association was observed between vitamin D and both TSH and T4 levels in younger adolescents aged 10\u0026ndash;14 years. These findings are in concordance with previous studies reporting significantly low levels of TSH and T4 in vitamin D deficient individuals aged 12 to 18 years [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and older than 18 years [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Vitamin D deficiency had been implicated in autoimmune thyroid disorders including Hashimoto\u0026rsquo;s thyroiditis and Graves`s disease [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Although, the exact mechanism by which vitamin D deficiency impairs thyroid functions is unknown, experimental evidence on mice model suggests that vitamin D exert its effect by increasing the mRNA expression of de-iodinase 2 gene, an enzyme necessary for conversion of T4 to T3 [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Other possible mechanisms include suppression of TSH-stimulated adenylyl cyclase activity and enhanced iodine uptake [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Several clinical trials have investigated the impact of vitamin D supplementation on thyroid function [\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Majority research reported a significant reduction in anti-thyroid antibodies following vitamin D supplementation with little or no effect on thyroid hormones levels [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. However, a larger clinical trial encompassing 11,017 participants mean aged 48\u0026thinsp;\u0026plusmn;\u0026thinsp;16 (18\u0026ndash;95 years) with 58% females, receiving vitamin D supplementation for 12 months reported both decrease in serum TSH, anti-TPO, anti-TG and TG levels over time and increase in serum FT3 and FT4 leading to reduction in hypothyroidism and thyroid autoimmune disorder [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong the trace elements, zinc exhibited a significant negative correlation with serum T3 and T4 and a positive, but non-significant, correlation with serum TSH levels. While this observation aligns with the findings of [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], it is important to note that other studies, such as those by [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] reported either no correlation or a positive correlation between zinc levels and thyroid hormones. These differences in findings highlight the need for further investigation into the specific mechanisms through which zinc interacts with thyroid hormones. Unlike the consistent role observed in other trace elements, zinc's influence on thyroid function appears to be complex and potentially context dependent. Zinc helps in thyroid metabolism through synthesis of the thyrotropin-releasing hormone (TRH) in the hypothalamus, as cofactor for deiodinase I and II enzyme that help in conversion of T4 to T3 or as structural component of T3 receptor [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, our study showed a positive association between T4 status and selenium levels. Selenium is a critical component of the deiodinase enzymes, which are responsible for the conversion of thyroxine (T4) into the more active triiodothyronine (T3) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. It exerts its effects on thyroid metabolism seleno-proteins, a group of biologically active protein molecules involved in diverse process including DNA synthesis and thyroid metabolism [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Research described the importance of adequate selenium levels for optimal thyroid function, highlighting how selenium deficiency can impair the conversion process, potentially leading to altered thyroid hormone levels and subsequent metabolic disturbances [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Moreover clinical research suggest that selenium deficiency is linked with a higher risk of elevated anti-thyroid antibody levels, while selenium supplementation has been shown to reduce thyroid peroxidase antibody levels [\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Selenium status has also been correlated with Grave\u0026rsquo;s disease [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], autoimmune hypothyroidism and thyroid cancer [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. In the context of adolescent Afghan refugees, who are likely exposed to a variety of environmental stressors and nutritional deficiencies, our findings of a positive association between T4 status and selenium levels suggest that selenium may play a crucial role in maintaining thyroid function amidst these challenges.\u003c/p\u003e \u003cp\u003eAlthough, our study is the first of its kind assessing the association between micronutrients status and thyroid function in vulnerable refugee population, it has some limitations. First, due to limited sample size and cross-sectional design, the study findings cannot be generalized to other refugee and host population. Secondly, we could not collect dietary data and other lifestyle factors which may also be associated with micronutrients status and thyroid profile in these population. None the less, the study provides important baseline data information regarding the potential impact of micronutrients on thyroid profile in a vulnerable population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, our study reports age and gender-based impact of different micronutrients (both vitamins and minerals) on thyroid function in adolescent Afghan refugees. Of these, vitamin D and zinc are especially important as the serum level of these micronutrients is significantly correlated with thyroid hormone levels in this population. These findings highlight the importance of close monitoring and effective nutritional interventions to prevent thyroid related disorders in vulnerable population such as refugees.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Board of the Khyber Medical University Pakistan vide letter number DIR/KMU-EB/PR/000766 dated 3 February 2020. Before recruitment, a written informed consent was obtained from all the participants and their parents.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was funded by a Seed Fund grant from the School of Biological Sciences (University of Reading) and supported by a BBSRC-DRINC grant (BB/N021800/1) to SCA. M.S. is recipient of Faculty Grant from Office of Research, Innovation and Commercialization (ORIC), Khyber Medical University.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.S performed the experimental work, data analysis, drafted and edited the manuscript. M.S; N.S and S.C.A. were involved in supervising the research and editing the manuscript. K.I; M.S.K and H.A.A in data collection, analysis and writing and revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank Commissionerate Afghan Refugees Khyber Pakhtunkhwa for facilitating data collection and ground support. We would also like to thank all the study participants for their time and participation in the study.\u003c/p\u003e\u003ch2\u003eAvailability of data and material\u003c/h2\u003e \u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRitchie H, Roser M, Micronutrient, Deficiency. 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J Trace Elem Med Biol. 2012;26(2\u0026ndash;3):168\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"thyroid-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thyr","sideBox":"Learn more about [Thyroid Research](http://thyroidresearchjournal.biomedcentral.com/)","snPcode":"13044","submissionUrl":"https://submission.nature.com/new-submission/13044/3","title":"Thyroid Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5349851/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5349851/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMicronutrients play crucial role in several metabolic processes including thyroid hormone metabolism and functions. The current study aimed to assess the associations between thyroid hormone levels and micronutrient status in a cohort of adolescents Afghan refugees residing in a refugee camp in Pakistan. A randomised, community based, cross-sectional study design was employed to recruit 206 adolescent (both male and female) Afghan refugees aged 10\u0026ndash;19 years. Sociodemographic data, anthropometric assessments and blood samples were collected using standard methods. Serum vitamins, minerals and thyroid hormones levels were assessed using ELISA, electrochemiluminescence and inductively coupled plasma mass spectrometry (ICP-MS) respectively. Overall results showed the median levels of T3 and TSH were significantly higher (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in younger adolescents (10\u0026ndash;14 years) compared to 15\u0026ndash;18 years old while T4 significantly higher in boys compared to girls. Correlational analysis between serum micronutrients status (vitamin D, vitamin B12, ferritin, folate, zinc, copper, selenium) and thyroid hormones revealed significant relationship in different age groups. Overall, vitamin D exhibits a statistically significant positive correlation with T4 (r\u0026thinsp;=\u0026thinsp;0.279) in the combined, younger (r\u0026thinsp;=\u0026thinsp;0.277) and older (r\u0026thinsp;=\u0026thinsp;0.319) age groups. In contrast, a statistically significant but negative correlation was observed when zinc levels were compared with T3 (r=-0.288) in the older age group and with T4 (r=-0.195) in the younger age group. In conclusion, micronutrients status especially vitamin D and zinc have important implications for thyroid health thereby requiring close monitoring of any thyroid deficiency related disorders in vulnerable population such as refugees.\u003c/p\u003e \u003cp\u003eClinical trial number: Not applicable\u003c/p\u003e","manuscriptTitle":"Impact of micronutrient status on thyroid function in adolescent Afghan refugees; a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-12 06:56:52","doi":"10.21203/rs.3.rs-5349851/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-10T11:30:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-10T05:34:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336926786538315740548896254961620787787","date":"2024-11-05T08:02:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81193308865592837083808671189108877166","date":"2024-11-04T02:10:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-03T10:34:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110252692366492071872957936045360744983","date":"2024-11-03T08:16:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-03T07:37:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-31T09:20:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-31T09:18:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Thyroid Research","date":"2024-10-28T22:13:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"thyroid-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thyr","sideBox":"Learn more about [Thyroid Research](http://thyroidresearchjournal.biomedcentral.com/)","snPcode":"13044","submissionUrl":"https://submission.nature.com/new-submission/13044/3","title":"Thyroid Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e5dff681-b9f0-4af3-b105-aaf5d7e54360","owner":[],"postedDate":"November 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T15:58:49+00:00","versionOfRecord":{"articleIdentity":"rs-5349851","link":"https://doi.org/10.1186/s13044-025-00239-6","journal":{"identity":"thyroid-research","isVorOnly":false,"title":"Thyroid Research"},"publishedOn":"2025-06-03 15:56:59","publishedOnDateReadable":"June 3rd, 2025"},"versionCreatedAt":"2024-11-12 06:56:52","video":"","vorDoi":"10.1186/s13044-025-00239-6","vorDoiUrl":"https://doi.org/10.1186/s13044-025-00239-6","workflowStages":[]},"version":"v1","identity":"rs-5349851","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5349851","identity":"rs-5349851","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}