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2026 Journal of Applied Sciences Research, 9(3): 2026-2032, 2013 ISSN 1819-544X This is a refereed journal and all articles are professionally screened and reviewed ORIGINAL ARTICLES Impact of Obesity on Thyroid Function in Children 1 Ahmed Ali Elaiady, 2Iman Abdelwahab Elashmawy, 3Sohair Abdelmawgod Abdelmaksoud, Hala Salah Megahed, 1Mohamed Farouk Mohamed, 2Mohammed Mahmoud Elbarawy 2 1 Pediatrics Dept., Faculty of Medicine, Cairo University, Egypt Child Health Dept., National Research Centre, Cairo, Egypt 3 Clinical Pathology Dept., National Research Centre, Cairo, Egypt 2 ABSTRACT Background: Obesity is considered to be a worldwide health problem with a steadily and dramatically increasing prevalence all over the world. Obese individuals are, in fact, at high risk of developing dyslipidemia, hypertension and impaired glucose tolerance, with consequent increase of the risk of metabolic and cardiovascular diseases Objectives: The aim of the study is to determine the effect of obesity on thyroid profile in children. Subjects and Methods: A cross sectional study comprised 90 children, 50 obese children of both sexes with a BMI of more than 95th percentile for age and sex, and 40 children of both sexes between (15th percentile-85th percentile) for age and sex serving as controls. Their age ranged from 6 to 10 years old. All cases and controls were subjected to full history taking and thorough clinical examination. All children were subjected to analysis of serum T3, T4, TSH and thyroid antibodies. Results: Our results showed that the mean TSH concentration was significantly higher in obese group 6.58 ± 4.74 μIU/mL compared with control group 1.95 ± 1.86 μIU/mL. The mean T3 concentration was significantly higher in control group 1.43 ± 0.49 ng/mL compared with obese group 0.81 ± 0.54 ng/mL. The mean T4 concentration was significantly higher in control group 8.52 ± 3.72 μg/dL compared with obese group 4.38 ± 3.10 μg/dL. The mean T.V hours/day was significantly higher in obese group 4.32 ± 1.15 hour compared with control group 2.73 ± 1.01 hour. It was noted that there is a significant difference between control group and obese group as regards food quality especially the mean of soda bottles per week, 1.45 ± 1.09 bottles in control group and 3.34 ± 1.64 bottles in obese group. Conclusion: Obesity is associated with hypothyroidism, lack of breastfeeding, increase TV watching hours and unhealthy eating habits, although, further studies should be done to identify the effect of weight reduction on thyroid profile in obese children. Key words: Obesity, Thyroid, BMI, Children. Introduction Obesity is considered to be a worldwide health problem with a steadily and dramatically increasing prevalence all over the world (Sokol, 2000). Obesity is defined by a body mass index (BMI) more than 95th percentile for age and sex (Khadilkar et al., 2007).Obese individuals are, in fact, at high risk of developing dyslipidemia, hypertension and impaired glucose tolerance, with consequent increase of the risk of metabolic and cardiovascular diseases (Nathan&Moran, 2008). The prevalence of obesity increases worldwide in the same time the understanding of its pathogenesis and metabolic consequences markedly advances. The white adipose tissue actively produces various hormones, cytokines, and chemokines, which play an important role in homeostasis and in thyroid hormone regulation (Rosen and Spiegelman, 2006). There has been an increasing attention to thyroid function in pediatric obese children (Stichel et al., 2000). Obesity affects hypothalamic-pituitary-thyroid axis directly or indirectly leading to alterations in thyroid function tests (Michalaki et al., 2006). Although thyroid function is usually normal in obese subjects, it is known that thyrotropin (TSH) and BMI are positively correlated. In fact, many studies in children, adolescents, and adults demonstrated that TSH levels are slightly increased in obese as compared to normal weight humans (Nyrnes et al., 2006). Massive obesity is rarely explained by hypothyroidism. We believe that many of obese children are unnecessarily treated with thyroid hormone replacement simply on the basis of mild TSH elevation (Bhowmick et al., 2007). Corresponding Author: Ahmed Ali Elaiady, Pediatrics Dept., Faculty of Medicine, Cairo University, Egypt 2027 J. Appl. Sci. Res., 9(3): 2026-2032, 2013 Materials and Methods This cross sectional study was carried out in children’s Hospital, Cairo University and the clinical pathology department of National Research Center during the period from July, 1st 2011 to April, 1st 2012. Children eligible for the study had the following inclusion criteria: Children from 6 to 10 years old of both sexes No organic or syndromic obesity Children who had clinical features of thyroid dysfunction other than obesity were excluded from the study. Ninety children were included, 50 obese children of both sexes with a BMI of more than 95th percentile for age and sex, and 40 children of both sexes between (15th percentile-85th percentile) for age and sex serving as controls. All cases and controls were subjected to the following: Full history taking including: Age and sex Symptoms suggestive of thyroid dysfunction Dietary history Family history of obesity, diabetes or hypertension Average hours of TV watching per day Organized sports practicing Thorough clinical examination: Vital signs Anthropometric measurements (weight, height and BMI) A child's weight status is determined using an age- and sex-specific percentile for BMI. BMI was defined as a child's weight in kilograms divided by the square of his height in meters (kg/m2). Egyptian Growth Charts were used to determine the corresponding BMI-for-age and sex percentile. For children and adolescents (aged 2—21 years): Obesity was defined as a BMI at or above the 95th percentile for children of the same age and sex (Barlow et al., 2007). Signs suggestive of thyroid dysfunction Presence of goiter Systemic features suggestive of syndromic obesity Laboratory investigations Total T3 Total T4 TSH Thyroid antibodies (thyroid peroxidase and thyroglobulin) Statistical analysis: Data were statistically described in terms of mean standard deviation ( SD), or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups was done using Student t test for independent samples. For comparing categorical data, Chi square (2) test was performed. Correlation between various variables was done using Pearson moment correlation equation, p values less than 0.05 was considered statistically significant. All statistical calculations were done using computer programs SPSS version 15 for Microsoft Windows. Results: This cross sectional study included Ninety children, 50 obese children (55.6%) with a BMI of more than 95th percentile for age and sex, and 40 children (44.4%) with a BMI between (15th percentile-85th percentile) for age and sex serving as controls. Out of the Ninety children, 41 were males (45.6%) and 49 were females (54.4%). The mean age of control and obese children, was 8.40 ± 1.32, and 8.28 ± 1.47 years respectively. Table (1) shows a comparison between children characteristics of control and obese groups, it revealed that the mean of T.V hours/day (p=0.000), soda bottles/week (p=0.000), weight (p=0.000), height (p=0.002), BMI (p=0.000), and systolic blood pressure (SBP) (p=0.014) were significantly higher in obese group than control group. 2028 J. Appl. Sci. Res., 9(3): 2026-2032, 2013 On comparing children characteristics of obese with normal TSH and obese with elevated TSH groups no statistically significant differences were detected regarding items shown in (Table 2). Comparison between biochemical characteristics of control and obese groups revealed significant difference regarding the mean of TSH (p=0.000), T4 (p=0.000) and T3 (p=0.000) (Table 3). A significant difference regarding the mean of TSH (p=0.000), T4 (p=0.001) and T3 (p=0.002) was detected when a comparison was done between biochemical characteristics of obese with normal TSH and obese with elevated TSH groups (Table 4). Comparison between thyroid peroxidase (TPO) of control and obese groups revealed no statistically significant difference (Table 5). No statistically significant difference was detected when a comparison between thyroglobulin (TG) of control and obese groups was done (Table 6). Table (7) revealed a significant difference between obese group and control group regarding number of breastfed children (p=0.000) and family history of chronic diseases (p=0.010). No correlation was detected between body mass index (BMI) and thyroid stimulating hormone (TSH) as shown in figure 1. Table 1: Comparison between children characteristics of control and obese groups control obese Item mean ± SD mean ± SD weaning age (month) 4.63 ± 1.25 4.32 ± 1.12 T.V hours/day 2.73 ± 1.01 4.32 ±1.15 soda/week(bottle) 1.45 ± 1.09 3.34 ± 1.64 meals/day 3.63 ± 0.94 3.78 ± 0.42 Weight (kg) 27.75 ± 4.94 48.18 ± 10.48 Height (cm) 125.48 ± 7.40 131.60 ± 9.82 BMI (kg/m2) 17.50 ± 1.67 27.40 ± 2.72 SBP (mmhg) 98.00 ± 5.16 100.60 ± 4.70 DBP (mmhg) 63.25 ± 4.74 65.20 ± 5.05 *P-value less than 0.05 is considered statistically significant. DBP: Diastolic blood pressure P-value 0.226 0.000* 0.000* 0.109 0.000* 0.002* 0.000* 0.014* 0.065 Table 2: Comparison between children characteristics of obese with normal TSH and obese with elevated TSH groups TSH Item P-value Normal Elevated mean ± SD mean ± SD weaning age (month) 4.62 ± 1.17 4.00 ± 0.98 0.050 T.V hours/day 4.23 ± 1.18 4.42 ± 1.14 0.574 soda/week(bottle) 3.19 ± 1.60 3.50 ± 1.69 0.512 meals/day 3.81 ± 0.40 3.75 ± 0.44 0.631 Weight (kg) 46.58 ± 9.90 49.92 ± 11.01 0.265 Height (cm) 130.81 ± 9.72 132.46 ± 10.05 0.558 BMI (kg/m2) 26.83 ± 2.57 28.02 ± 2.80 0.125 SBP (mmhg) 100.38 ± 3.44 100.83 ± 5.84 0.740 DBP (mmhg) 64.62 ± 5.08 65.83 ± 5.04 0.399 *P-value less than 0.05 is considered statistically significant. Table 3: Comparison between biochemical characteristics of control and obese groups control obese Item mean ± SD mean ± SD TSH (μIU/mL) 1.95 ± 1.86 6.58 ± 4.74 T4 (μg/dL) 8.52 ± 3.72 4.38 ± 3.10 T3 (ng/mL) 1.43 ± 0.49 0.81± 0.54 *P-value less than 0.05 is considered statistically significant. P-value 0.000* 0.000* 0.000* Table 4: Comparison between biochemical characteristics of obese with normal TSH and obese with elevated TSH groups TSH Item P-value Normal elevated mean ± SD mean ± SD TSH (μIU/mL) 3.46 ± 2.53 9.95 ± 4.24 0.000* T4 (μg/dL) 5.78 ± 3.01 2.86 ± 2.46 0.001* T3 (ng/mL) 1.03 ± 0.51 0.58 ± 0.49 0.002* *P-value less than 0.05 is considered statistically significant 2029 J. Appl. Sci. Res., 9(3): 2026-2032, 2013 Table 5: Comparison between thyroid peroxidase of control and obese groups Group Normal TPO Positive Total Total Control Obese Count 38 47 85 % within Group 95.0% 94.0% 94.4% Count 2 3 5 % within Group 5.0% 6.0% 5.6% Count 40 50 90 % within Group 100.0% 100.0% 100.0% P-value 0.606 *P-value less than 0.05 is considered statistically significant. Table 6: Comparison between thyroglobulin of control and obese groups Group Normal TG Positive Total Count Control Obese 38 46 Total P-value 84 % within Group 95.0% 92.0% 93.3% Count 2 4 6 % within Group 5.0% 8.0% 6.7% Count 40 50 90 % within Group 100.0% 100.0% 100.0% 0.450 *P-value less than 0.05 is considered statistically significant. Table 7: Number of breastfed children, family history and exercise rates of control and obese groups control obese (n=40) (n=50) Item N % N Breast feeding 34 85 24 Family history of chronic diseases 6 15 27 Exercise or sports 7 17.5 3 *P-value less than 0.05 is considered statistically significant P-value % 48 54 6 0.000* 0.010* 0.085 Fig. 1: Correlation between BMI and TSH in obese and control groups Discussion: Obesity in childhood is increasing worldwide. In recent years, there has been increasing focus on the relationship between thyroid function and weight status. Whereas it is well known that hyperthyroidism leads to weight loss and hypothyroidism is associated with weight gain, changes in thyroid homeostasis that occur in obesity are controversial (Reinehr, 2011). In our study, it was noted that the mean TSH concentration was significantly higher in obese group 6.58 ± 4.74 μIU/mL compared with control group 1.95 ± 1.86 μIU/mL. 2030 J. Appl. Sci. Res., 9(3): 2026-2032, 2013 Our study comes in agreement with the study done by Bhowmick et al., (2007) who studied 308 obese children and 286 non obese children. Elevated TSH levels were noted in 36 patients within the obese group (11.7%) but only two in the control group (<0.7%). Reinehr and Andler, (2002); Reinehr et al., (2006); Reinehr et al., (2008); Kumar et al., (2009); Grandone et al., (2010) found similar results. TSH elevation in obese group may be due to inflammatory cytokines secreted by adipose tissue which affect thyroid cells and also increased leptin mediated production of pro-TRH (Reinehr, 2011). Our results come in contradiction to the Marras et al., (2010) who studied 468 obese children and 52 normal-weight children as controls from children attending the Obesity Clinic of the Pediatric Endocrine Unit of the Regional Hospital for Microcytemia, Cagliari, Italy during the years 2003–2006. The mean TSH concentration was almost the same in obese group 2.4 ± 0.05 mU/l compared with control group 2.17 ± 0.1 mU/l, but one of the limitations in the study was that the control group included children with short stature and other minor complaints. In our study, it was noted that the mean T4 concentration was significantly higher in control group 8.52 ± 3.72 μg/dL compared with obese group 4.38 ± 3.10 μg/dL. Also the mean T3 concentration was significantly higher in control group 1.43 ± 0.49 ng/mL compared with obese group 0.81 ± 0.54 ng/mL. Our study comes in agreement with Sari et al., (2003) who studied 98 obese women and 31 non obese, and found that FT3 and FT4 were lower in obese women compared to control but in the normal levels, Shon et al., (2008) who studied 1572 euthyroid women found that obese euthyroid women had lower FT4 levels than did lean euthyroid women, Knudsen et al., (2005) found similar results. These results can be explained by the negative feedback between TSH and the peripheral hormones. Our results come in contradiction to the Reinehr and Andler, (2002) who studied 118 obese children and 107 healthy children of normal weight from children attending the intervention program (Obeldicks) for obese children between 1999 and 2000. They found that T3 and T4 were significantly higher in obese children compared to those of normal weight, Reinehr et al., (2006) who studied 246 obese and 71 normal weight children, found that no significant difference in FT4 levels between obese and normal weight children. However these studies failed to explain how TSH is elevated in presence of high T3 and T4 or even normal levels and its negative pituitary feedback. The effects of changes in body weight on thyroid function and thyroid volume are controversial, probably due to different study designs (human or animal), subject population and iodine status (Sari et al., 2003). This pattern supports that alterations in thyroid function with normal pituitary feedback regulation (low T4 and T3 associated with high TSH) is the primary event, and alterations in BMI via alterations in energy expenditure the secondary event (Knudsen et al., 2005). Missed cases of hypothyroidism in Egypt may be attributed to lack of routine check up for children especially the obese, even the results of neonatal thyroid screening are delivered to the parents by phone. Iodine deficiency also may be a cause of hypothyroidism in Egypt, but it was not measured in our study. In our study, hypothyroidism cannot be explained by autoimmune thyroiditis as it was noted that out of 40 of normal weight children, 2 children were with positive TPO (5%) and 2 children were with positive TG (5%) and out of 50 obese children, 3 children were with positive TPO (6%) and 4 children were with positive TG (8%) which is higher but not significant. Stichel et al., (2000) found similar results as out of 123 obese children 6 (4.8%) were with positive TG and 4 (3.2%) were with positive TPO, the obese subgroup of 17 who had elevated TSH also had higher percentage of positive thyroid antibodies (25.5% for TPO and 17% for TG). Bhowmick et al., (2007) found that 5 out of the 36 in the obese subgroup with elevated TSH levels had positive thyroid antibodies (14%), Radetti et al., (2008) found that out of 186 overweight and obese children, 43 children showed positive antithyroid antibodies, but no control groups in both studies. In our study, it was noted that the mean T.V hours/day was significantly higher in obese group 4.32 ± 1.15 hour compared with control group 2.73 ± 1.01 hour. Dennsion et al., (2002) found that a two percent increase in the prevalence of obesity has been documented for each extra hour per day of TV viewing. Our study comes in agreement with the study done by Suresh et al., (2011) who found that TV viewing in adolescence and early adulthood was found on change in BMI over time, with excess gains of between 0.011 and 0.013 kg/m2 per year for those watching TV most frequently. Watching TV produces sedentary life style, sedentary children tend to watch more TV, so it is vicious circle. Also, watching TV means exposure to advertisement for food products. In our study, it was noted that out of 40 of normal weight children, 34 children were breast fed (85%), and out of 50 obese children, 24 children were breast fed (48%). Gillman et al., (2001) found that children who had been breastfed for at least 12 months have lower weightfor-height values than those breastfed for shorter durations Our study comes in agreement with the meta-analysis done by Harder et al., (2005) who found that the duration of breastfeeding is inversely and linearly associated with the risk of overweight. The risk of overweight 2031 J. Appl. Sci. Res., 9(3): 2026-2032, 2013 was reduced by 4% for each month of breastfeeding, Beyerlein et al., (2008) who studied 14,412 children participating in the school-entry health examination in Bavaria, Southern Germany, found a lower proportion of overweight and obese children among breastfed children. In our study, it was noted that out of 40 of normal weight children, 7 children were on exercise or sports (17.5%), and out of 50 obese children, 3 children were on exercise or sports (6%) but the results did not reach statistical significance. Klijn et al., (2007) who studied fifteen pediatric patients with obesity recruited from the pediatric department of Treatment Center Heideheuvel at Hilversum, Netherlands; found at the end aerobic training for six weeks that the mean BMI before the study was 37.4 ± 3.5 kg/m2 and after the study was 32.7 ± 2.7 kg/m2. 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