Thyroid hormonal status among children with obesity

Introduction

Thyroid hormones are closely linked to the processes involved in growth and development and free T4 (FT4) and thyroid-stimulating hormone (TSH) levels are presumed to be related to obesity [Knudsen et al. 2005; Reinehr, 2010, 2011]. Recently, there has been an increasing focus on thyroid function in obesity [Reinehr, 2011]. Thyroid hormones and TSH concentration are reported to be normal, elevated, or even low in people with obesity in comparison to normal weight individuals [Grandone et al. 2010; Nyrnes et al. 2006; Reinehr et al. 2006; Tagliaferri et al. 2001; Iacobellis et al. 2005].

In children with obesity, TSH and thyroid hormone concentrations are shown to be high [Aypak et al. 2013; Dekelbab et al. 2010; Gertig et al. 2012; Nyrnes et al. 2006], which is accompanied by some abnormalities in this population, including weight gain, increased cholesterol levels, impaired growth velocity, anemia, sleepiness, weakness, and impaired psychomotor and cognitive development [Aijaz et al. 2006; Wu et al. 2006]. Although there are various studies evaluating the thyroid hormone and TSH levels in children with obesity and possible related complications [Chen et al. 2013; Marras et al. 2010; Marwaha et al. 2013], the findings are inconsistent [Danese et al. 2000; Knudsen et al. 2005].

In this study we aim to evaluate T4 and TSH concentrations among normal children and those with obesity to assess possible correlations between obesity and these markers.

Materials and methods

Anthropometrical measurements

Body weight to the nearest 0.1 kg was measured with a digital balance and height to the nearest 1 mm was measured with a stadiometer (Holtain, Wales, UK). BMI was calculated as weight divided by squared height (kg/m²). We measured subjects wearing light indoor clothing and no shoes.

Biochemical parameters

Thyroid function was assessed by measuring serum concentrations of TSH, FT3, FT4 and total T4. A blood sample was drawn in the morning after 12 h of fasting. Serum samples were obtained from whole blood after clotting. Serum TSH, total and free thyroxine, and free triiodothyronine were analyzed using solid phase technique chemiluminescence immune assays (Roche Diagnostics, Mannheim, Germany). Reference values for thyroid function test were as follows: TSH (mIU/ml, reference range 0.5–5) and FT4 (ng/dl, reference range 0.8–2.3), T4 (μg/dl, reference range 5.5–12.8) and FT3 (3.7–8.6 pmol/liter).

Data analysis

All data were analyzed using the Statistical Package for Social Sciences, version 17.0 (SPSS, Chicago, IL, USA). Baseline data are reported as mean ± standard deviation (continuous data) or percentages (categorical data), depending on the data level. In order to analyze the differences between the groups in the quantitative variables, Student’s t-test was used in those with normal distribution and the Mann–Whitney U test if the distribution was not normal. The association between qualitative variables was studied by means of χ² test or Fisher’s exact test. The correlation between BMI and thyroid function test was evaluated using Pearson’s correlation. A p value of 0.05 or less was considered significant.

Results

In this study, 190 children who were overweight or obese and 133 nonobese controls were evaluated. Table 1 demonstrates demographic and anthropometric findings, and thyroid function test results for both groups.

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Table 1.

Demographic, anthropometric and laboratory findings between groups.

		Children with obesity	Controls	p value
Age (years)		9.12 ± 3.18	9.11 ± 3.27	0.97
Sex	Male	72 (37.9%)	56 (42.1%)	0.44
	Female	118 (62.1%)	77 (57.9%)
Weight (kg)		47.78 ± 18.38	26.93 ± 9.58	<0.001*
Height (cm)		134.16 ± 16.74	127.18 ± 18.82	0.001*
BMI z score		4.38 ± 1.80	−0.33 ± 0.97	<0.001*
TSH (mIU/ml)		3.41 ± 1.96	2.63 ± 1.52	<0.001*
Total T4 (μg/dl)		10.03 ± 2.04	9.18 ± 1.73	<0.001*
Free T4 (ng/dl)		1.55 ± 0.37	1.52 ± 0.34	0.57
Free T3 (pmol/liter)		6.20 ± 1.50	6.11 ± 1.37	0.57

BMI, body mass index; TSH, thyroid-stimulating hormone.

*

p is two-sided significant.

Children who were overweight or obese had significantly higher TSH and total T4 levels compared with children without obesity, but the difference in FT3 and FT4 was not significant. TSH and subclinical hypothyroidism were significantly increased in children with obesity (28 cases, 14.7%) compared with control subjects (10 cases, 6.8%, p = 0.04). Total T4 was increased in 18 (9.5%) children with obesity and 5 (3.8%) normal controls (p = 0.04). Among children with obesity and increased TSH levels, only three children (10.7%) had positive results for TPO-Ab and TG-Ab.

The correlation between thyroid function tests with BMI z score was evaluated and we found a significantly positive correlation between BMI z score and TSH level (r = 0.198, p < 0.001) and T4 level (r = 0.18, p = 0.001), but the correlations between BMI z score and FT3 (r = 0.08, p = 13) and FT4 (r = 0.08, p = 0.13) were not significant (Figure 1).

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Figure 1.

Correlation between body mass index (BMI) z score and serum thyroid-stimulating hormone (TSH) (a), total T4 (b), free T3 (c) and free T4 (d).

Discussion

In this study, we evaluated TSH, FT3, FT4, and total T4 levels in normal children and those with obesity and also assessed the correlation between thyroid function tests and BMI. TSH and total T4 levels and subclinical hypothyroidism were significantly higher in children with obesity compared with normal subjects.

Similarly, it is shown that TSH and the peripheral thyroid hormones (T3 and T4) are increased in obesity [Stichel et al. 2000]. Similar to our findings, other studies have reported elevated serum TSH in children with obesity compared with normal subjects [Bhowmick et al. 2007; Michalaki et al. 2006; Stichel et al. 2000] and are confirmed by other studies performed in children who are obese or overweight, and those of normal weight [Radetti et al. 2008; Rapa et al. 2009]. Unlike some studies that showed significantly increased FT3 concentrations in children with obesity [Marras et al. 2010], we found no significant increase in FT3 and FT4 levels.

In this study, we also observed a significant positive correlation between TSH levels and BMI; with an increase in BMI z score, the mean TSH was also increased. Similar findings were also reported by Solanki and colleagues [Solanki et al. 2013]. However, some other studies showed no evidence of an association between thyroid status within the normal range and BMI [Manji et al. 2006].

The reason for the increase in serum TSH in subjects with obesity, both adults and children, is not clear. There are several suggested mechanisms which may lead to increased TSH levels in obesity; these mechanisms are increased leptin-mediated production of pro-Thyrotropin-releasing (pro-TRH) hormone [Nillni et al. 2000], impaired feedback due to a lowered number of T3 receptors in the hypothalamus [Burman et al. 1980], and a decrease in peripheral deiodinase activity [Krotkiewski, 2002]. Although the exact underlying mechanism is not understood, the observation that weight loss leads to decreased TSH levels implies that an increase in TSH in subjects with obesity is reversible and seems to be a consequence rather than a cause of obesity [Reinehr et al. 2006].

The prevalence of elevated TSH is reported to be between 1% and 21% among children and adolescents with obesity [Bhowmick et al. 2007; Michalaki et al. 2006; Stichel et al. 2000]. It is reported that elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in children and adolescents with obesity [Dekelbab et al. 2010]. The prevalence of an elevated TSH level in our study (14.7%) was within the reported range, which was also significantly higher than normal controls. Similar to previous reports, we observed thyroid antibodies in only three cases (10.7%) of children with obesity and elevated TSH levels.

Subclinical hypothyroidism in our study was 14.7% in children with obesity which was significantly higher than normal controls (5.8%). Similar to our findings, Namburi and colleagues reported subclinical hypothyroidism in 15% of patients with obesity [Namburi et al. 2014], while another study by Hari Kumar and colleagues showed a higher incidence (26%) [Hari Kumar et al. 2008]. It is reported that subclinical hypothyroidism in children and adolescents is a benign and remitting process with low risk of evolution toward overt hypothyroidism [Bona et al. 2013]. It is also found that weight loss frequently restores these abnormalities [Marras et al. 2010]. Considering these findings and due to possible complications of subclinical hypothyroidism, weight loss programs should be considered to prevent these problems, although TSH levels would reduce over time.

This study has some limitations and strengths. A large case and control group is a strength of the current study, which makes the results more obvious and clear. However, we did not record the occurrence of any complications and we did not follow up the children with subclinical hypothyroidism and so we cannot give accurate results for remission of high TSH levels and related complications.

Conclusion

In conclusion, TSH and total T4 levels are increased in children with obesity and are a common finding in these children, but the incidence of thyroid antibodies is low in these patients and so could not be accounted for by thyroid autoimmunity. Due to these findings it is possible that increased TSH and total T4 levels could be reduced by decreasing BMI.