Aim: To determine the effects of obesity on thyroid functions in children
Material and Method: The records of 132 patients who were followed up in our Pediatric Endocrinology and Diabetes Division with the diagnosis of obesity from March 2006 to May 2009, were investigated retrospectively. Anthropometric measurements, serum lipid profiles, thyroid hormone levels, fasting blood glucose and insulin levels were evaluated. TSH levels of patients whose HOMA-IR <3.16 and HOMA-IR >3.16 were compared. Correlation between TSH levels and HOMA-IR, BMİ (body mass index) was investigated. Statistical evaluation was done using SPSS 13.0 statistical program. For comparasion of independent groups chi-square and for correlation analysis “Pearson method” were used. p<0.05 was accepted as significant.
Results: Seventeen patients’ (12.9%) TSH levels were above 97.5 persentile, fifty one patients’ (38.7%) TSH levels were above 90 persentile. None of the patients whose TSH levels were above 97.5 persentile, has low free/ total T4 levels. There was no significant difference in the TSH levels, when the patients whose HOMA-IR <3.16 and HOMA-IR >3.16 were compared. There was an insignificant, positive, weak correlation between TSH levels and HOMA-IR, BMI.
Conclusions: TSH levels of obese children may be elevated without any change in the peripheral thyroid hormone levels. This situation should not be evaluated as hypothyroidism and not be started L- throxine treatment in the first examination. (Turk Arch Ped 2011; 46: 33-6)
In recent years, obesity has become an important health problem threatening public health. It is known that obesity affects endocrine functions and its effects on thyroid functions in children and adolescents and their clinical implications are emphasized. In many studies, serum TSH levels have been shown to be higher in obese adults, adolescents and children compared to individuals without obesity, but no reduction in free and total T4 level accompanied this state
(1-6). In this study, it was aimed to investigate the effects of obesity on thyroid hormones in children and the relation of these effects with the degree of obesity and insulin resistance.
Material and Method
One hundred thirty two patients who were followed up in the Division of Pediatric Endocrinology and Diabetes in Kocaeli University Medical Faculty with the diagnosis of obesity from March 2006 to May 2009 and whose thyroid functions were evaluated were investigated retrospectively. A Body Mass Index (BMI) higher than the 95th percentile was considered as obesity. BMI percentiles were assessed according to the study performed by Bundak et al (7) in 2006 for children with an age of 6 years and older and according to CDC (centers of disease control and prevention) data of 2000 for children older than 6 years (8). Subjects with known history of thyroid disease were excluded from the study. Antropometric measurements, serum TSH, free T4 and/or total T4 level, serum lipid levels, thyroid hormone levels, fasting blood glucose and insulin levels were recorded and HOMA-IR value was calculated (fasting insulin x fasting blood glucose (mmol/L)/22.5). Thyroid hormone levels were assessed according to the range in the age-appropriate source (9). Treshold value for HOMA-IR was considered to be >3.16 and subjects with a value higher than this were classified as subjects with positive insulin resistance (10). Thyroid functions in the study group were compared in the subjects with positive insulin resistance and negative insulin resistance and by the degree of obesity. Data were analysed on SPSS 13.0 Statistical Program. Comparisons for independent groups were done with chi-square test and correlation analysis was done with Pearson method. A p value of <0.05 was considered statistically significant.
Eigthy three (62.9%) of 132 subjects recruited to the study were female and 49 (37.1%) were male. Mean age was 11.9±3.18 years (5.1-17.9). 24% of the subjects (n:32) were in the preadolescence period, 33% (n:44) were in the middle of adolescence and 43% (n:56) had completed adolescence. Mean BMI (Body Mass Index) value was 30.61 ±4.65 (21.7-42) and mean BMI Standard deviation score (SDS) was found to be 2.79±0.62 (2-5.7). Acanthosis nigricans was present in 76 of the subjects (57.6%). HOMA-IR was >3.16 in 50% of the subjects and <3.16 in 50% of the subjects. Mean HOMA-IR value was 1.9±1.02 in the subjects in the preadolescence period, 3.07±1.7 in the subjects in the adolescence period and 5.69±8.7 in the subjects who had completed adolescence. Mean serum insulin level was found to be 16±10.57 (1.0-69) mU/mL. Mean TSH level of the subjects was found to be 3.42±1.57 mU/mL (0.77-9.0). TSH level was between the 90th and 97.5th percentile according to age in 34 subjects (25,8%) and above the 97.5th percentile in 17 subjects (12,9%). In a total of 51 subjects (38.7%), TSH level was found to be above the 90th percentile. Thyroid autoantibodies were found to be negative in the subjects with TSH level above the 90th percentile. Free T4 (fT4) level was evaluated in 116 subjects and was found to be between the 10th and 97.5th percentile in 109 (94%) and above the 97.5th percentile in 7 (6%). Mean free T4 was found to be 16.84±4.2 pmol/L. fT4 level was not below normal in any subject in the group with a TSH level above the 97.5th percentile. fT4 levels in the subjects with TSH level above the 97.5th percentile are shown in Table 1. Total T4 level was evaluated in 52 subjects and the mean value was found to be 9.27±1.89 mg/mL (6.15-14.50). Mean serum cholesterol level was found to be 165.1±33.9 mg/dl and mean triglyceride level was found to be 111.1±53.7 mg/dl. Mean HDL cholesterol level was 44.5±9.3 mg/dl and mean LDL cholesterol level was 99±27.4 mg/dl. Anthropometric parameters and laboratory findings of the subjects are shown in Table 2. The subjects were divided into two groups; one group with a HOMA-IR value higher than 3.16 (group 1, n:66) and the other group with a HOMA-IR value lower than 3.16 (group 2, n:50). When TSH levels of these two groups were compared, no statistically significant difference was found (p=0.697) (Table 3). When the subjects were divided into two groups according to BMI SDS values with one group with a BMI SDS value between 2 and 3 (n:85) and the other group with a BMI SDS value of >3 (n:46), no statistically significant difference was found in terms of TSH levels (p<0.05) (Table 4). There was an insignificant, positive, weak correlation between TSH levels and HOMA-IR and BMI (Table 5).
In recent years, many studies about the effects of obesity on thyroid functions have been conducted and serum TSH levels have been shown to be mildly higher in obese children, adolescents and adults compared to individuals without obesity (1-5). It is known that no change in free or total T4 levels accompany this mild increase in TSH level (3, 5, 6). High TSH levels were found in 7.5% of 290 obese children in the study performed by Stichel et al. (11) and in 10.8% of 185 obese children in the study performed by Bassem et al. (12). Similarly, THS level was found to be above the 97.5th percentile in 13% (n:17) of 132 subjects included in the study group in our study and this rate is close to the rates reported in the literature. It has been shown that increase in peripheral thyroid hormones may be present along with high TSH levels in obese children. The cause of this is not completely known, but it is thought that it might be caused by thyroid hormone resistance similar to insulin resistance (13). In our study, however, fT4 levels were found to be normal in the subjects with high levels of TSH.
Although the effect of obesity on TSH has not been fully elucidated yet, it has been shown that this is not related to iodine deficiency or autoimmune thyroiditis (5,6,11,13). The fact that evidence of autoimmune throiditis was not found in any of the subjects with high TSH level supports literature information (5,6,11,13). In our country, iodine protection is being performed since 1998 by use of iodized salt and a marked decrease in iodine deficiency has been achieved, but still the prevalence of moderate-severe iodine deficiency was reported to be 27.8% in a publication reporting the current iodine status (14). Since our study was performed retrospectively, urine iodine levels were not assessed in the subjects. This may be evaluated as a weak point in our study.
In the studies performed recently, it has been suggested that adipose cells contain numerous TSH receptors and this explains the relation between obesity and TSH (15). It is known that TSH production is regulated by some neurotransmitters (neuropeptide-Y, melanocyte-stimulating hormone, agouti-related peptide) which regulate body weight and satiety. In addition, some studies have shown a positive correlation between leptin level and TSH (16-18).
Some studies have shown a positive correlation between body mass index and TSH level (2,19). However, 20 overweight children were compared to 30 obese children in terms of TSH level in the study performed by Kumar et al. (20) published in 2009 and no statistically significant difference was found between the two groups. Again in the same study, no relation was found between TSH level and BMI (20). In our study, no statistically significant difference was found in TSH levels between the groups with a BMI SDS value of 2-3 and >3 and no statistically significant correlation was found between TSH level and BMI.
Some studies have shown a strong correlation between TSH level and insulin resistance and BMI in obese individuals (20,21). In our study, however, no statistically significant correlation was shown between HOMA-IR and TSH level.
In a study comparing TSH levels before and after weight reduction, the finding that no significant decrease in TSH levels occured after weight reduction suggested that the cause of obesity in these patients was a neuroendocrine dysfunction leading to bioinactive TSH release (13). However, the same investigator compared TSH levels before and after weight reduction in 240 obese children and found that there was a significant decrease in TSH level with weight reduction and emphasized that high TSH level was a result of obesity rather that a cause based on these findings (5). Eliakim et al.(22) showed that thyroxine treatment had no positive effect in children with high TSH.
Conclusively, thyroid functions should be interpreted meticulously, peripheral thyroid hormones should be measured (especially T4) and acquired hypothyroidism should be excluded in obese children. In subjects with normal T4 levels and mildly increased TSH level, it should be kept in mind that this is a result of obesity, rather than a cause and starting treatment on the first evaluation should be avoided.
Conflict of interest: None declared
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