Gynecomastia in adolescent males: current understanding of its etiology, pathophysiology, diagnosis, and treatment.

Gynecomastia (GM) is a common and continuously evolving condition that commonly occurs during adolescence. It is the source of significant embarrassment and psychological stress in adolescent males. GM is characterized by enlargement of the male breast due to the proliferation of glandular ducts and stromal components. The main cause of GM during adolescence is physiological or pubertal GM, which is primarily attributed to an imbalance between estrogen and androgen activity. Physiological GM is typically transient and resolves within several months, although it may take several years to resolve. GM may also be caused by other pathological conditions and could be indicative of an endocrine disease. It is crucial to understand the pathogenesis of GM to distinguish it from normal developmental variants due to pathological causes. The aim of this review is to highlight the significance of GM during adolescence in terms of potential etiologies, clinical and laboratory diagnoses, and current management.

Idiopathic ketotic hypoglycemia in children: an update.

Idiopathic ketotic hypoglycemia (IKH) is defined as bouts of hypoglycemia with increased blood or urine ketones in certain children after prolonged fasting or during illness. IKH is divided into physiological IKH, which is most frequently observed in normal children with intercurrent acute illness, and pathological IKH, which occurs in children who lack counter-regulatory hormones, have a metabolic disease, or have Silver-Russell syndrome. The typical patient is a young child between the ages of 10 months and 6 years. Episodes nearly always occur in the morning after overnight fasting. Symptoms include those of neuroglycopenia, ketosis, or both. IKH may be diagnosed after ruling out various metabolic and hormonal conditions associated with ketotic hypoglycemia. Sufficient amounts of carbohydrates and protein, avoidance of prolonged fasting, and increased frequency of food ingestion are the main modes of treating IKH. It is crucial to understand the pathogenesis of IKH and to distinguish physiological IKH from pathological IKH. In this mini-review, we present a brief summary of IKH in terms of its definition, types, clinical presentation, diagnosis, and therapeutic approach in children.

Ovarian reserve in adolescent girls with autoimmune thyroiditis

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Graves' Disease in Children: An Update.

Graves' disease (GD) is the most common cause of hyperthyroidism in children. A common GD symptom is a goiter. The usual biochemical profile in children with GD is a decreased thyroid hormone stimulating hormone (TSH) level and high free thyroxine (FT4) and free triiodothyronine (FT3) concentrations. The presence of thyroid receptor antibodies (TRAb) is the most important specific immunological sign for diagnosing GD. The treatment choices for pediatric GD are anti-thyroid drugs (ATDs), radioiodine, and thyroidectomy, but the risks and benefits of each modality are different. Management recommendations include the first-line use of a prolonged course of ATDs for at least 3 years and potentially 5 years or more. Rituximab and Teprotumumab are new novel alternative medications for the treatment of adult patients with GD and Graves' orbitopathy respectively, but evidence of the efficacy and safety of these drugs in pediatric patients with GD is lacking.

Endothelial dysfunction in children with newly diagnosed Graves' disease.

The most frequent cause of hyperthyroidism in children is Graves' disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries' intima-media thickness and the brachial artery's FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32-5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45-3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16-2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18-8.23, P = 0.001).  Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible. What is Known: • Graves' disease is the most common cause of hyperthyroidism in children. • vWF is a reliable marker for detection of vascular endothelial dysfunction. What is New: • Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level. • Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.

Ovarian reserve in adolescent girls with autoimmune thyroiditis.

Objective: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusion: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Subclinical hyperthyroidism in children.

Subclinical hyperthyroidism (SH) is defined as serum thyroid-stimulating hormone (TSH) below the lower limit of the reference range in the presence of normal free T4 and free T3 levels. Depending on the degree of TSH suppression, SH could be defined as mild (TSH, 0.1-0.45 mU/L) or severe (TSH<0.1 mU/L). Patients with SH are often asymptomatic when symptoms are present, they are similar to the symptoms in patients with overt hyperthyroidism, although they are usually milder. The management of the SH is uncertain and should be individualized. We present this review after an extensive literature search and long-standing clinical experience. This review provides the prevalence, causes, clinical presentation, investigation, and therapeutic approach of SH in children.

Urinary C-peptide creatinine ratio is a significant indicator of non-alcoholic fatty liver disease in children with obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest etiology of chronic hepatic problems in children with obesity. This study aimed to assess whether urinary C-peptide creatinine ratio (UCPCR) might be a potential indicator of NAFLD in obese children. METHODS: The study included 240 children with simple obesity. Hepatic ultrasonic examination, anthropometric and laboratory measurements including fasting plasma glucose, fasting insulin, fasting C peptide, liver, renal profile, lipid profile, and UCPCR were obtained in all cases. According to the results of the hepatic ultrasonography, cases were classified into two categories, those with NAFLD (n=98) and without NAFLD (n= 142). RESULTS: In cases with NAFLD, UCPCR was significantly higher than those without NAFLD (P &lt; 0.001). A significant positive correlation between UCPCR and waist circumference (WC SDS), triglyceride, fasting C-peptide, HOMA-IR and alanine aminotransferase (ALT) was found (P &lt; 0.001 for each). Adjusting for other variables, UCPCR was the most significant predictor of NAFLD in children with obesity with higher odds ratio (OR = 3.26) than fasting C peptide (OR = 2.87), triglyceride (OR = 1.89), ALT (OR = 2.20), WC SDS (OR = 1.32) and age (OR=1.27) . UCPCR cut-off value of 0.755 nmol/mmol was able to discriminate cases with NAFLD from those without NAFLD with a sensitivity of 95%, a specificity of 87%. CONCLUSIONS: We concluded that UCPCR is a useful, practical and non-invasive predictor of NAFLD in children with obesity with high sensitivity and specificity.

Endocrinal dysfunction in children with Down syndrome.

Down syndrome (DS) is the most common genetic disorder in live-born infants. Children with DS are at increased risk of numerous endocrinal comorbidities. The information contained in this article will provide pediatricians with a narrative overview of different presentations, diagnoses, and management recommendations of various endocrinal disorders in children with DS. We systematically searched PubMed, Embase, Google Scholar, MEDLINE, EBSCO, and Science Direct, and potentially relevant articles were identified and retrieved from electronic and print journals.

Vestibular function for children with insulin dependent diabetes using cervical vestibular evoked myogenic potentials testing.

BACKGROUND: Healthy vestibular system adjusts balance during static and dynamic conditions. This is important for normal development (standing up and walking). Vestipulopathies (central and peripheral) are common complications of diabetes in adult population. Related studies are scare in children with type 1 diabetes (T1D). AIM: To assess saccular function of otolith organ in children with T1D and predictors for its dysfunction. METHODS: Cervical vestibular evoked myogenic potential (cVEMP) was used for objective evaluation. RESULTS: The study included 40 patients (boys = 15; girls = 25). Patients had mean age of 13.63 ± 1.50 years, duration of diabetes of 5.62 ± 2.80 years, frequent attacks of diabetic ketoacidosis (55%) and hypoglycemia (30%), hyperlipidemia (20%), hypertension (12.5%) and peripheral neuropathy (40%). Dizziness was found in 10%. Compared to healthy children (n = 25), patients had prolonged cVEMP P1 and N1 latencies and reduced P1-N1 amplitude. Bilateral cVEMP abnormalities were found in 60% (vs 25% for unilateral abnormalities). Higher frequencies and severe vestibulopathies were found with chronic diabetes of > 5 years, hemoglobin A1c values > 7%, frequent diabetic ketoacidosis and hypoglycemic attacks and presence of dizziness. Regression analyses showed that predictors for prolonged P1 latencies and reduced P1-N1 amplitudes were only chronic diabetes (> 5 years) {odds ratio (OR) = 2.80 [95% confidence interval (CI): 1.80-5.33], P = 0.01; OR = 3.42 (95%CI: 2.82-6.81)} and its severity (hemoglobin A1c > 7%) [OR = 3.05 (95%CI: 2.55-6.82), P = 0.01; OR = 4.20 (95%CI: 3.55-8.50), P = 0.001]. CONCLUSION: Dysfunction or injury of the saccular macula and its pathways is prevalent in children with T1D. Optimum glycemic control is important to prevent diabetes related vestipulopathies.

Association of Epicardial Fat with Diastolic and Vascular Functions in Children with Type 1 Diabetes.

We aimed to examine the relationship between epicardial fat thickness (EFT) measured by echocardiography and cardiovascular functional parameters in children with type 1 diabetes mellitus (T1DM). The study included 50 type 1 diabetic children and 50 healthy subjects matched by sex, age, and body mass index. In addition to laboratory tests, all participants underwent transthoracic echocardiography for EFT, cardiac dimensions and left ventricular functions, and ultrasonographic examination for brachial artery flow-mediated dilation (FMD) response and carotid intima-media thickness (CIMT). Multivariate linear regression was used to analyze the relationship between EFT and CIMT, FMD, lateral mitral E' velocity, and mitral E/E' ratio. EFT was significantly increased in diabetic children compared with controls (P < 0.001). In comparison with controls diabetic children had significantly increased mitral A, decreased lateral mitral E', decreased mitral E/A ratio, decreased lateral mitral E'/A' ratio, and increased mitral E/E' ratio (P < 0.001). FMD response was significantly lower in diabetic group versus controls (P < 0.001) and CIMT was significantly increased in diabetics versus controls (P = 0.03). EFT was negatively correlated with lateral mitral E' velocity (r = - 0.613, P < 0.001), positively correlated with mitral E/E' ratio (r = 0.60, P < 0.001), positively correlated with CIMT (r = 0.881, P < 0.001), and negatively correlated with FMD (r = - 0.533, P < 0.001). By multivariate regression analysis, the EFT was independently and positively associated with CIMT mean and E/E' mean and negatively associated with FMD mean and E' mean. The cut-off point for EFT as predictor of endothelial dysfunction was 6.95 mm. Our findings suggest that children with T1DM have subclinical LV diastolic and vascular endothelial dysfunctions associated with increased EFT.

Hormone resistance in children: what primary care physicians need to know.

Hormone resistance is defined as a reduced or absence of  target tissues responsiveness to a hormone, where the presentation is related to either a relative lack or excess of hormones. Various disorders of hormone resistance were encountered including, Laron syndrome, nephrogenic diabetes insipidus, thyroid hormone resistance syndrome, pseudohypoparathyroidism, insulin resistance, familial glucocorticoid deficiency, pseudohypoaldosteronism, X linked hypophosphatemic rickets  and androgen insensitivity syndrome. The article gives a summary that presents, in concentrated form, what the primary care physicians need to know about recognition,  clinical presentation, diagnosis, and management  of various hormone resistance in children.

Subclinical hypothyroidism in children: updates for pediatricians.

Subclinical hypothyroidism (SH) is defined as serum thyroid-stimulating hormone (TSH) above the upper limit of the reference range in the presence of normal free T4 concentrations. Depending on the degree of TSH elevation, SH could be defined as mild (TSH, 4.5-10 mIU/L) or severe (TSH>10 mIU/L). While there is a general consensus to treat children with serum TSH levels above 10 mU/L, the management of the mild form is uncertain and should be individualized. In this mini-review, we present a brief review of SH in children based on extensive literature review and long-standing clinical experience. This review provides the prevalence, causes, clinical presentation, consequences, investigation, and up-to-date therapeutic approach of SH in children. Generally, the purpose of the review is to provide pediatricians with an update of this common and continuously evolving condition.

Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia.

BACKGROUND AND AIMS: Patients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients. METHODS: The study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups. RESULTS: Compared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = -0.54, p = 0.001), high-sensitivity CRP (r = -0.53, p = 0.001), HOMA-IR (r = -0.31, p = 0.01), CA-IMT (r = -0.22, p < 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = -0.022, p < 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001). CONCLUSIONS: Our study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control.

OBJECTIVE: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. METHODS: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. RESULTS: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. CONCLUSION: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.

Midkine: Utility as a Predictor of Early Diabetic Nephropathy in Children with Type 1 Diabetes Mellitus

Objective: This study aimed to assess the role of serum midkine (MK) as a biomarker for early detection of diabetic nephropathy in children with type 1 diabetes mellitus (T1DM) before microalbuminuria emerges. Methods: A total of 120 children with T1DM, comprising 60 microalbuminuric patients (Group 1), 60 normoalbuminuric patients (Group 2), and 60 healthy participants as a control group (Group 3) were included. Detailed medical history, clinical examination, and laboratory assessment of high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c percentage (HbA1c%), lipid profile, urinary albumin to creatinine ratio (ACR), serum MK and estimated glomerular filtration rate based on serum creatinine were performed in all participants. Results: Both Group 1 and Group 2 had significantly higher serum MK compared to controls (p<0.001). Additionally, significantly higher MK concentrations were present in Group 1 compared with Group 2 (p<0.001). Receiver operating characteristic curve analysis revealed that the MK concentration cutoff value of 1512 pg/mL was able to predict microalbuminuria with a sensitivity of 96% and specificity of 92%. Stepwise regression analysis revealed that HbA1c%, hs-CRP, and ACR were independently related to MK levels (p<0.001 for each). Conclusion: The results of this study suggest that serum MK is a useful, novel, practical marker for the evaluation of renal involvement in children with T1DM, especially in normoalbuminuric children.

Ferritin levels in children and adolescents with type 1 diabetes mellitus: relationship with microvascular complications and glycemic control

ABSTRACT Objective: Evaluate ferritin levels in children and adolescents with type 1 diabetes mellitus and its relation to diabetic microvascular complications, and metabolic control. Subjects and methods: This study included 180 children and adolescents with type 1 diabetes mellitus (T1DM) with a mean age of 14.9 ± 3.1 years and 180 apparently normal children matched for age and sex (control group). All children were evaluated with full history taking, thorough clinical examination, laboratory assessment of high-sensitivity C-reactive protein and hemoglobin A1c (HbA1c), and evaluation of the presence of microvascular complications. Serum ferritin levels were measured using electrochemiluminescence immunoassay. The patients were divided into two groups according to the presence or absence of microvascular complications. Results: Serum ferritin levels were significantly higher in patients with T1DM in both groups compared with healthy controls (p < 0.001). Additionally, patients with microvascular complications had higher serum ferritin concentrations than those without microvascular complications (p < 0.001). Patients with microalbuminuria showed higher ferritin levels compared with patients without microalbuminuria (p < 0.05). Stepwise regression analysis revealed that levels of HbA1c and urinary albumin excretion were independently related to ferritin levels (p < 0.001 for both). On receiver operating characteristic (ROC) curve analysis, a ferritin cutoff value of 163.6 ng/mL differentiated patients with microvascular complications from those without microvascular complications with a sensitivity of 92.1% and specificity of 93.4%. Conclusion: Serum ferritin levels are elevated in T1DM, particularly in patients with microvascular complications.

Food sensitization in preschool Egyptian children with recurrent wheezing.

BACKGROUND: Food allergy is common in children with prevalence up to 10%. We assessed the clinico-laboratory characteristics and frequency of food sensitization to the commonly consumed food among upper Egyptian preschool children with recurrent wheezy chest. METHODS: This cross-sectional descriptive study was conducted on 100 preschool children with recurrent wheezy chest recruited from Emergency, Allergy, and Pulmonology units, Assiut University Children's Hospital, Egypt. All enrolled patients were subjected to history taking, through examination, chest X-ray, skin prick testing (SPT), and lab investigations. RESULTS: Family history of allergy was found in 66 patients, while history of other allergies was reported in 47 patients. History of food allergy was positive in 47% of the studied patients, and 28 patients had positive reaction by SPT. Sensitization to fish, milk, egg, and wheat was found in 15, 8, 5, and 4 patients, respectively. Eighteen out of the 28 patients who were sensitized by SPT gave positive history of food allergy, while ten patients had no suggestive history; also, history suggestive of food allergy was negative in 35.7% of sensitized patients versus 61.1% of non-sensitized patients. CONCLUSIONS: Food sensitization is common in preschool Egyptian children with recurrent wheezing. IMPACT: Food sensitization is common in children with prevalence up to 10%, and in atopic children up to 30%. Sensitization to fish was the most common type of sensitization observed among preschool children with recurrent wheezing, followed by milk, eggs, and wheat, respectively. SPT aided by history is a good screening tool to determine whether patients need to avoid some foods that can cause allergy in order to help in controlling their symptoms.

Soluble CD40 Ligand Levels in Children with Newly Diagnosed Graves' Disease

Objective: Soluble CD40 ligand (sCD40L) is elevated in various autoimmune disorders, which may have diagnostic and therapeutic implications. The aims of the current study were to evaluate serum sCD40L concentrations in children with newly diagnosed Graves' disease (GD) and to correlate its levels with patients' clinical and laboratory parameters. Methods: This study included 48 children with newly diagnosed GD and 48 healthy children. Serum thyroid-stimulating hormone (TSH) (TSH, fT4 and fT3), TSH receptor antibodies (TRAbs), high sensitivity C-reactive protein (hsCRP) and sCD40L levels and thyroid volume were measured. Results: Compared to control subjects, children with GD had higher thyroid volume standard deviation scores (SDS) (p=0.001), and higher levels of hsCRP (p=0.001), TRAbs (p=0.001) and sCD40L (p=0.001). Significant correlations were found between sCD40L and age (p=0.01), thyroid volume SDS (p=0.001), hsCRP (p=0.01) and TRAbs (p=0.001). In multivariate analysis, sCD40L concentrations were correlated with TRAbs [odds ratio (OR)=3.1, 95% confidence intervals (CI): 2.2-2.7, p=0.001] and thyroid volume SDS (OR=2.1, 95% CI: 1.2-2.7, p=0.001). Conclusion: This preliminary study has evidence of high concentrations of sCD40L in children with newly diagnosed GD and a correlation between sCD40L and both TRAbs and thyroid volume, which may indicate a biologically active role for sCD40L in the pathogenesis of GD.

Epicardial Fat Thickness in Children with Subclinical Hypothyroidism and Its Relationship to Subclinical Atherosclerosis: A Pilot Study.

BACKGROUND/AIMS: Thyroid hormones (TSH) play a key role in the working of the cardiovascular system, with direct effects on cardiac function, vascular system, and atherosclerotic factors. Epicardial adipose tissue, the visceral fat of the heart, has emerged as a new cardiometabolic risk marker because of its close anatomical proximity to the myocardium and coronary artery. This study aimed to evaluate epicardial fat thickness (EFT) in children with subclinical hypothyroidism (SH) and its relation to early atherosclerotic changes. METHODS: The study included 32 children with SH due to autoimmune thyroiditis and 32 healthy children matched for age and gender as control group. Patients and controls underwent anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance and high-sensitivity C-reactive protein (hs-CRP). TSH, free thyroxine (FT4 and FT3) and antithyroid autoantibodies (antithyroid peroxidase and thyroglobulin antibodies) were also measured. Conventional echo-cardiography was used to assess EFT. Noninvasive ultrasound was used to measure carotid intima-media thickness and brachial artery flow-mediated dilation (FMD) responses. RESULTS: Compared to controls, patients had higher atherogenic index (AI) and hs-CRP (p = 0.001 for each). Conventional echocardiography revealed that patients with SH had higher EFT (p = 01) and significantly lower FMD response compared with the control (p = 0.001). In multivariate analysis, EFT values were significantly correlated with TSH (OR 1.2; 95% CI 1.04-1.34; p = 0.01), hs-CRP (OR 1.1; 95% CI 1.09-1.14; p = 0.001, AI (OR 1.6; 95% CI 1.17-2.03; p = 0.001), and FMD response (OR 2.4; 95% CI 1.14-2.53; p = 0.01). CONCLUSIONS: Our study demonstrated that EFT is higher in children with SH compared with controls and associated with FMD responses. Measurement of EFT by echocardiography in children with SH may help to identify those at high risk of developing subclinical atherosclerosis.