Can Epicardial Adipose Tissue be Defined as an Early Marker of Treatment Decisions of Subclinical Hypothyroidism in Childhood?

  

    

    

    
EAT0 
    
EAT6 
    
P value 
  
  

    
 
      
SH1 
    
Prepubertal 

      Pubertal 

      Total 
    
3,39±1,09 

      5,24±0,53 

      4,08±1,41 
    
2,99±1,15 

      4,74±0,44 

      3,65±1,27 
    
0,001 
  
  

    
 
      
SH2 
    
Prepubertal 

      Pubertal 

      Total 
    
3,42±1,12 

      5,33±0,93 

      4,31±1,09 
    
3,41±0,83 

      5,01±0,65 

      4,16±1,10 
    
0,013 
  
  

    
Total 
    
Prepubertal 
    
3,40±1,10 
    
3,15±1,04 
    
0,002 
  
  

    
SH 
    
Pubertal 
    
5,28±0,73 
    
4,87±0,55 
  

Table 4: Comparison of EAT0 and EAT6 in Patients with and Without Treated.

Discussion

With the widespread use of screening tests in recent years, the incidence is increasing in childhood and adolescents. But the consensus among endocrinologists is still unclear for the treatment of the disease. If childhood SH is not treated, it is highly likely to go hypothyroidism. Especially in untreated cases in the first year of life, obvious hypothyroidism and consequent growth retardation and the possibility of developing neurocognitive dysfunction may become a potential and insidious threat to children in the era of development. For this reason, it is very important to know this clinical entity well, to take precautions early and to minimize the loss.

Subclinical hypothyroidism is higher in girls than in boys [12]. In our study, SH group consisted of 26 (52%) of the patients and 24 (48%) of the males. The iodine status is also very important in the etiology of SH. The incidence of iodine deficiency in our study was 16%.

Measuring serum TSH concentration is the most sensitive test to show thyroid function [13,14]. However, the difficulty in defining normal TSH value may differ from the clinician in establishing SH. Until the diagnosis of SH, treatment is a controversial clinical entity, and no precise criteria have yet been established for treatment. L-T4 therapy in patients with TSH <10 mIU/l in children without symptoms is highly controversial and there are limited studies in this issue [15]. In our study, mean TSH level of SH patients treated was 6.56±3,02 (mIU/mL) and TSH level of non-treated group (SH2) was 5.68±1.05 (mIU/mL). Likewise, the mean fT4 value of SH1 was 1.24±0.16 (ng/mL) and the sT3 value was 4.45±0.66 (ng/mL). Mean fT4 value of the non-treated group was 1.26±0.13 (mIU/mL) and fT3 value was 4.22±0.63 (ng/mL). Although subclinical hypothyroidism is not shown clinical findings, many studies have shown that SH causes abnormalities in lipid metabolism and increase in serum cholesterol levels parallel to serum TSH levels. [16] In our study, we excluded cases with dyslipidemia in particular, so we aimed to investigate the effect of SH on EAT without the presence of dyslipidemia.

The incidence of coronary heart disease and the increase in mortality in SH cases were found to be correlated with TSH >7 mIU/L [17]. It is known that L-T4 treatment in children and adults alleviates apparent hypothyroid cardiac function [18]. In the literature, there are only two studies showing cardiac functions in childhood group SH cases. However, two of these studies include cases of Down syndrome and obesity. Toscano et al., studied left ventricle funcitons of 16 patients with Down’s syndrome (mean age 65.5 months, mean TSH 7.8 mIU/L), and 25 healthy euthyroid children (mean age 70.3 months, mean TSH 3,2 mIU/L) , and they did not find any significant difference. However, this result of studying is attributed to the early ages of the cases and the short follow-up period [19]. In another study comparing cardiac functions in obese SH cases and euthyroid healthy children, the left ventricular function of the obese SH group was significantly lower than the control group [20]. Left ventricular functions were found to be significantly lower in SH cases in another study where left ventricular function was assessed. There was a significant increase in left ventricular systolic and diastolic function after 6 months of L-T4 therapy [16]. In the literature, there is not efficient information about the effect of L-T4 treatment on cardiac function in children with isolated SH.

Epicardial adipose tissue thickness is another important marker in terms of cardiovascular risks [21,22]. There are some studies in the adulthood which explore the relationship between SH and EAT, and also some studies take place in the literature which examine the relationship between EAT and L-T4 treatment in SH [21,23-27]. However there are very limited studies in childhood which explore the relationship between SH and EAT, and there is no study in childhood which examine the relationship between EAT and L-T4 treatment in SH. Asik G et al., studied a total 50 children (25 SH and 25 without thyroid dysfunction), they found that EAT was significantly higher than children without thyroid dysfunction. Likewise, the EAT of SH cases were found to be significantly higher than the control group [28,29]. Farghaly et al., Studied a total of 64 children (32 SH and 32 without thyroid dysfunction), of which all of the SH group consisted of cases due to autoimmune thyroiditis, they found that the EAT of SH cases were found to be significantly higher than the control group [30]. In our study, we observed that mean EAT0 of not treated SH cases was 4,31±1,09 mm and the mean EAT0 thickness of treated SHs (SH1) was determined as 4,08 ± 1,41 mm.

Myocardial Performance Index (MPI) is an easy method for evaluating systolic and diastolic cardiac function [31]. In a study by Yazici et al., which compares SH events and control group in adults at 2014, MPI value pf SH group was found to be significantly lower than the control group and it was shown that the decrease in MPI with L-T4 treatment was reversible. In the same study, the EAT thickness was found to be higher in the SH group than in the control group, and a 6-month L-T4 treatment reduced the EAT thickness [32]. We also found that the decrease in EAT in the group who receive L-T4 therapy was more prominent. In addition, we found that the mean EAT6 thickness in the SH1 group was 3.65±1.27 mm, while the EAT6 thickness in the SH2 group was 4.16±1.10 mm. Statistically significant decrease was detected in EAT6 compared to EAT0, and the decrease in EAT in SH1 group was statistically more significant (p <0.005). The reduction in the EAT thickness of the SH2 group was thought to be associated with conventional therapy. The SH1 group was thought to be more effective for the SH2 group at the 6^th month for the L-T4 treatment.

In our study, statistically significant relationship was found between the values of EATs in SH group and age. The EAT thickness increased with age (p <0.05). This may be related to the increase in visceral adipose tissue as age increases. Significant correlations were found between EAT and BMI in previous adult studies [33]. There are contradictory publications in the literature regarding the relationship between BMI and EAT. Vertical measurements of the EAT with the ECO have been reported previously as an independent indicator of visceral adipose tissue, but as a weak indication of the degree of obesity measured by BMI [25]. Ahn et al., found that there was a significant association among the groups with the EAT vertical measurement above and below 3 mm in terms of BMI [33]. In our study, a statistically significant relationship was found between SH and the control group in terms of BMI and EAT thickness. As the BMI level increases, the EAT thickness also increases (P <0.05). Ergur et al., found a statistically significant increase in body adipose percentage (Fatmass) was found when bioelectrical impedance and body composition were evaluated in children with SH (especially adolescents) study [34]. In SH cases, this result may be the cause of the increase in EAT. These two findings are the earliest developing parameters and may be effective for future treatment decisions.

The rate of apparent hypothyroidism was higher in patients with high thyroid autoantibody titers and also have hypoecogenic thyroid ultrasonography [3]. If the anti-TPO antibody is not positive in a case with SH, the rate of progression to having an apparent hypothyroid is determined as 2.6%, whereas it is 4.3% when anti- TPO is positive [35]. Scott et al., claim that the presence of goiter and anti-Tg positivity at the time of admission, and the increase in anti- TPO antibody and TSH levels in the follow-up were two predictive markers of developing apparent hypothyroid development in these cases [36]. Radetti et al., stated that increased thyroid volume and anti-thyroid antibodies were found to be associated with a higher risk of developing SH in these patients with impaired thyroid function [7]. In our study, a statistically significant relationship was found between the anti-TPO and Anti-Tg groups in the SH group. The positive value of Anti TPO and Anti Tg increase the EAT thickness (P <0.05). A statistically significant correlation was found between the EAT values and the thyroid parenchyma size in the SH group. There was an inverse proportion between thyroid parenchyma measure and EAT. (P <0.05). These data suggest that thyroid antigens and thyroid parenchymal may be effective in predicting the increase in the EAT thickness.

In conclusion, in our study, epicardial adipose tissue thickness was significantly higher in children with subclinical hypothyroidism than children without thyroid dysfunction. This study suggests that adverse effects on the cardiovascular system have begun in children with SH without developing apparent hypothyroidism. The significant value of our study is that EAT measurements can provide a clear criterion, especially in the presence of highly controversial L-T4 treatment decision in childhood. Perhaps future EAT will take place in the literature as a criterion for starting treatment in children with SH. The increase in the number of cases with longer follow-up period may be important to support this view.

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