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

Original Article

J Pediatri Endocrinol. 2021; 6(1): 1041.

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

Asik G¹, Ergur AT²* and Sanli C³

1Department of Pediatrics, Kirikkale University Faculty of Medicine, Turkey

2Department of Pediatric Endocrinology, Ufuk University Faculty of Medicine, Turkey

3Department of Pediatric Cardiology, Kirikkale University Faculty of Medicine, Turkey

*Corresponding author: Ayca Torel Ergur, Department of Pediatric Endocrinology, Ufuk University Faculty of Medicine, Ankara, Turkey

Received: January 21, 2021; Accepted: February 15, 2021; Published: February 22, 2021

Abstract

Introduction and Aim: Childhood overt hypothyroidism is a chronic disease that affect many system adversely and requires treatment. However, Subclinical Hypothyroidism (SH), defined obvious cases, impacts on other systems are unknown and there is no common approach to be treated. Moreover, SH may continue for many years, before they become overt hypothyroidism. Cardiovascular System (CVS) is one of the host system, which hypothyroidism adversely affects. Epicardial Adipose Tissue Thickness (EAT) is known to be an important marker in terms of the cardiovascular risks. We aimed to determine the effects on CVS in children with SH.

Material and Methods: The study included were 100 cases, which are 1-18 years had categorized in two groups; control group (50 children), who had no signs of thyroidal dysfunction and case group (50 children) who had diagnosed with SH, are recruited in the study. SH was diagnosed according to the slightly higher TSH than the upper limit (4.2M/L), normal free T4 and T3 levels. Medical treatment (LT4) was decided according to the levels of TSH, sT3, sT4 and clinical status. EAT was determined by transthoracic echocardiographic measurements in millimeters. The SH cases were classified into two groups in terms of medical treatment. EAT thickness was measured in patients with treated group (SH1) and non-treated group (SH2) at admission (EAT0) and at 6 months (EAT 6).

Results: Epicardial adipose tissue thickness was significantly higher in SH children, than the children without thyroid dysfunction. The mean value of the EAT in control group was 2,11±0,52 mm. Mean of EAT0 was 4,08±1,41 in group SH1, mean of EAT0 was 4,31±1,09 mm in group SH2. In addition, mean of EAT6 was 3.65±1,27 mm in group SH1 and mean of EAT6 was 4,16±1,10 in group SH2. Although there were a decrease in both group SH1 and SH2, at EAT6 compared to the EAT0, and this decrease was more significant in group SH1.

Discussion: This study suggests that subclinical hypothyroidism effects adversly the cardiovascular system in children before hypothyroidism become overt. In future, this data may be marker at the begining of LT4 treatment in SH with children.

Keywords: Childhood subclinical hypothyroidism; Epicardial adipose tissue thickness

Introduction

Thyroid hormones have great effect on growth, puberty and human metabolism [1] Childhood overt hypothyroidism is a chronic disease that affects many systems adversely and requires treatment. However, effects of Subclinical Hypothyroidism (SH), which is defined by obvious cases with higher TSH and normal free T4 (fT4) on other systems are unknown and there is no common approach to be treated [2]. For that reason, SH can be defined as “devious danger of childhood”. Moreover, SH may continue for many years, before they become overt hypothyroidism. Prevalence of subclinical hypothyroidism is reported about 2% in children, prevalence of SH in general population is reported about 1-12.4 % in some studies [3- 6]. However, screening of thyroidal function, which becomes a part of routine laboratory examinations, showed higher than expected prevalence of SH in patients with family history of thyroidal disease or presence of goiter [4-6]. As a result, that disease with great importance clinically is defined as the tip of the iceberg.

Clinical findings in patients with subclinical hypothyroidism could varied from asymptomatic to typical hypothyroidism [3]. Goiter, decline in school success, especially in maths, growth failure, low height and weight percentiles, or loss of percentile of height/weight refractory iron deficiency anemia, dyslipidemia (hypocholesteremia) could be presented in that cases. Symptoms like negativism, panic attack, depression, attention deficiency in children foreshow the SH [8]. However, laboratory findings in SH are also often overlooked. The treatment decision varies greatly and there is no common approach to treatment. For this reason, it is necessary to clarify the criteria for initiation of treatment. This need requires further research in this regard.

Cardiovascular System (CVS) is the one of the main system, which hypothyroidism adversely affects. It is well known that EAT is an important marker for cardiovascular risks [9]. Although EAT has some protective effects on cardiovascular risk, such as metabolic and mechanic status; increased EAT levels are linked with negative outcome. There is a casual relationship between EAT and various diseases, such as obesity, insulin resistance, hypertension, atherosclerosis and metabolic syndrome. EAT is a good predictor of visceral lipidosis than waist circumference, because EAT is not affected by skin and muscle, like waist circumference. In that study, we aimed to evaluate the EAT in children with SH and observe the effect of SH on EAT in children. This study is the first study, which investigates that relationship.

Material and Methods

Material and Methods 100 cases whose age ranged between 1 to 18 years are included in this study; 50 cases were diagnosed SH (SH group), 50 cases, who had no signs of thyroidal dysfunction were defined as healthy control group (control group). SH was diagnosed in children who had slightly higher TSH than the upper limit (4.2M/L), fT4 and fT3 within the normal limit. Control group were defined as children who applied to pediatric endocrinology clinic with the symptoms of fatigue, sleep disorder and nervousness and whose routine laboratory examinations were normal. Obese children, children with dyslipidemia and/ or tendency to have dyslipidemia, malignancy, diabetes, chronic diseases like cardiovascular, metabolic syndrome and hepatic, renal disorders; children who use drug regularly are excluded from the study. After having a detailed medical information about children; antropometric (chronological age, bone age, weight, height, BMI), physical examination and thyroid examination (WHO UNICEF) of all SH-diagnosed cases were performed. Thyroid function tests (fT3, fT4, TSH), thyroid antibodies, spot urine iodine, hemogram, ferritin, zinc, vitamin D (25OHD), vitamin B12 and folate were analyzed to evaluate the thyroidal dysfunction. Serum lipid and homocysteine levels were analyzed to exclude the coronary artery disease. Decision of medical treatment (LT4) is based on both symptoms, clinical and laboratory findings of SH cases. Cases who received medical treatment were defined as group SH1, cases who received conventional treatment were defined as group SH2. L-T4 treatment is started with the low dose of 2 μg/kg/day and dose was followed up with TSH and fT4 measurement in every four weeks. SH2 cases who had diagnosed with apparent hypothyroidism in the follow-up period, had excluded from the study. Patient whose TSH level >20 mIU/L had excluded from the study. With the reason to determine the underlying cause of SH, patients were screened for thyroid autoantibodies, thyroid USG and spot urine iodine.

Epicardial adipose tissue thickness ratios were assessed by same cardiologist using transthoracic echocardiography using 2-D and M-Mode techniques on a General Electric Vivid 7 device with 2.5- 3.5 MHz transducer in the left lateral decubitus position after resting for 10 minutes. In two-dimensional echocardiographic examination, EAT was measured at the end of parasternal long-axis diastole, from the 1/3 section of the ventricular basal, which is adjacent to the right ventricular free wall at vertical, horizontal and cross-sectional sections. EATs of all SH group patients were assessed at 0, (EAT 0) and 6 months (EAT 6). EAT 0 was measured for all control group patients (Figure 1).