Τriglycerides-glucose (TyG) index is a sensitive marker of insulin resistance in Greek children and adolescents.

PURPOSE: To investigate the association between Triglyceride-glucose (TyG) index and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Matsuda indices in Greek obese children and adolescents, in order to assess whether it could be used as a predictor of insulin resistance. METHODS: 367 children (47.7% boys) with mean age of 9.9 ± 2.3 years, who were investigated for obesity, were included. After overnight fasting, TyG and HOMA-IR indices were calculated in all participants. In a subpopulation of 72 children Matsuda index was also calculated. RESULTS: 48.8% and 36.1% of the participants had insulin resistance according to HOMA-IR and Matsuda index respectively. TyG was significantly and positively correlated with BMI, ΗΟΜΑ-IR, lipid profile and Matsuda index. ROC curve analysis for TyG showed that the optimal cutoff value for the prediction of insulin resistance (HOMA-IR) was 7.96 with sensitivity 65% and specificity 58%. The area under the curve (AUC) was 0.65 which significantly differs from 0.5 (p < 0.001). Similarly, the optimal cutoff value of TyG index for predicting insulin resistance as evidenced by Matsuda was 7.91 with sensitivity 85% and specificity 61%. The AUC was 0.75 (p < 0.001). The odds for insulin resistance (with HOMA-IR) was 2.54 times greater for subjects with TyG higher than 7.96, while the odds for insulin resistance (with Matsuda) was 8.56 times greater for subjects with TyG more than 7.91. CONCLUSIONS: TyG index shows a positive correlation with insulin resistance among children and adolescents, however further studies are needed to clarify its predictive ability.

17p13.1 Microduplication Syndrome in a Child, Familial Short Stature, and Growth Hormone Deficiency: A Case Report and Review of the Literature.

To date, 6 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability is the core feature, together with minor facial dysmorphisms and obesity. We describe the first case of a young patient with a maternally inherited microduplication in 17p13.1 presenting with growth hormone deficiency. The boy was addressed to the endocrine division for growth retardation (weight and height <3rd percentile). Besides minor facial dysmorphisms, physical and neurological examinations were normal except for motor dyspraxia. Basic blood tests and endocrinological investigations were normal, but IGF1 levels were low for his age. Growth hormone deficiency was confirmed. Hypothalamic pituitary MRI was normal. His karyotype was 46XY. Array-CGH analysis detected a 422-kb copy number gain in the spanning region 17p13.1 inherited from his mother. Although familial short stature is considered a "normal" variation of growth retardation, hormonal and genetic investigation is essential in the etiological diagnosis.

Cortisol response to adrenocorticotropin testing in non-classical congenital adrenal hyperplasia (NCCAH).

BACKGROUND: The adequacy of cortisol response in non-classical congenital adrenal hyperplasia (NCCAH) has not been fully elucidated. The aim was to evaluate cortisol response to adrenocorticotropin (ACTH) stimulation test in children and adolescents with NCCAH and heterozygotes for CYP21A2 gene mutations. METHODS: One hundred and forty-six children and adolescents, mean age 7.9 (0.7-17.5) years with clinical hyperandrogenism, were evaluated retrospectively. Thirty-one subjects had NCCAH, 30 were heterozygotes for CYP21A2 gene mutations, while 85 showed normal response to ACTH test. RESULTS: Baseline cortisol levels did not differ among NCCAH, heterozygotes, and normal responders: 15.75 (5.83-59.6) µg/dL vs. 14.67 (5.43-40.89) µg/dL vs. 14.04 (2.97-34.8) µg/dL, p=0.721. However, NCCAH patients had lower peak cortisol compared to heterozygotes and control group: 28.34 (12.25-84.40) vs. 35.22 (17.47-52.37) µg/dL vs. 34.92 (19.91-46.68) µg/dL, respectively, p=0.000. Peak cortisol was <18 µg/dL in 7/31 NCCAH patients and in one heterozygote. CONCLUSIONS: A percentage of 21.2% NCCAH patients showed inadequate cortisol response to ACTH stimulation. In these subjects, the discontinuation of treatment on completion of growth deserves consideration.

Epidemiological characteristics of children with autoimmune thyroid disease.

OBJECTIVE: Chronic autoimmune thyroiditis (AT) is the most common cause of thyroid disease in children. The aim of the study was to define the epidemiological clinical and laboratory characteristics of children and adolescents with AT. DESIGN: Various parameters including thyroid ultrasonography of 228 children and adolescents aged 10.2 ± 2.5 yrs (mean ± SD) with AT, who attended our Pediatric Endocrine Unit during a 5-year period were retrospectively analysed. RESULTS: 191 (83.8%) were female and 142 (62.3%) were pubertal. At AT diagnosis, 130 children (57.0%) were euthyroid, 75 (32.9%) had subclinical hypothyroidism, 19 (8.3%) had hypothyroidism and 4 (1.8%) had hyperthyroidism. There was a positive correlation between thyroid stimulating hormone (TSH) levels and thyroid volume SDS (r=0.15, p=0.02). Sixty-three children (28%) had a goiter and 32 (14%) had thyroid nodules. Three children (1.3%) had papillary thyroid carcinoma. Compared to euthyroid children, children with hypothyroidism were younger (9.2 ± 1.8 vs 10.6 ± 2.4 yrs, p<0.05) and had higher thyroid volume SDS (3.1 ± 1.9 vs 1.2 ± 1.2, p<0.05) and higher prevalence of goiter [11(57.9%) vs 29(22.3%), p<0.05]. CONCLUSIONS: Children and adolescents with AT are mostly asymptomatic; the majority are female, pubertal and euthyroid. Hypothyroid children with AT have higher thyroid volume, higher prevalence of goiter and higher antithyroid antibodies titers compared to euthyroid children. Diagnosing AT at an early stage offers the opportunity for a timely intervention. The potential association of AT with papillary thyroid carcinoma is an additional reason for a careful follow-up of the patients with AT.

Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM).

It has been suggested that cytokine release during DKA may result in capillary perturbation and thus may contribute to the development of its acute clinical complications (i.e.cerebral or pulmonary edema). We studied in 38 newly diagnosed T1DM children with DKA, aged 7.68±3.07 years, plasma levels of cytokines IL-1ß (interleukin-1ß), IL-2, IL-6, IL-8, IL-10, TNF-α (tumour necrosis factor-α) and also WBC (white blood cell count), hs-CRP (high sensitivity C-reactive protein), GH (growth hormone) and cortisol, prior to, during and 120h after DKA management, with the aim to monitor their levels at different time-points and in different degrees of DKA severity. Prior to DKA management the levels of IL-6, IL-8, IL-10, WBC and cortisol were elevated, but were all reduced within 120 h after DKA management. Then the patients were divided into two groups: a. moderate/severe: pH≤7.2, b. mild DKA: pH>7.2. In the group with moderate/severe DKA (ph≤7.2), IL-10 levels were the highest of all cytokines, but were significantly decreased after 6h (91.76 vs 18.04 pg/mL, p=0.008), with no further change, while IL-6 levels were decreased at 120 h (28.32 vs 11.9 pg/mL, p=0.003). The above were not observed in the group with mild DKA. In conclusion, in the children with DKA of our study, in the group with moderate/severe DKA the IL-10 levels were prematurely reduced at 6 hours, while the IL-6 levels remained high and were reduced at 120 hours after the DKA management. These changes may be responsible for increased capillary perturbation, which could lead to the subsequent development of acute DKA complications.

The prevalence and risk factors for coeliac disease among children and adolescents with type 1 diabetes mellitus.

AIMS: Our aim was to determine in children with T1DM the prevalence of positive antibodies against tissue transglutaminase (anti-tTG IgA) as indices of coeliac disease (CD), as well as its clinical presentation, its determinants and its association with thyroid (anti-TG, anti-TPO) and pancreatic b-cell autoimmunity (anti-GAD). METHODS: The study included 105 children and adolescents with T1DM, aged (mean±SD) 12.44±4.76 years, with a T1DM duration of 4.41±3.70 years. RESULTS: Fifty of our patients (47.6%) were positive for anti-GAD, 9/105 (8.6%) for anti-tTG IgA and 21/105(20%) for anti-thyroid antibodies. The anti-tTG IgA (+) children, in comparison with the rest of the study population, were of younger age (9.31 vs. 12.74 years, p=0.038), shorter diabetes duration (2.16 vs. 4.62 years, p=0.056) and had mild growth impairment (height SDS: -0.55 vs. +0.20, p=0.055). Univariate logistic regression analysis revealed that the presence of anti-tTG IgA (+) was associated with younger age and shorter T1DM duration. Only 5/9 (55.6%) children with high titres of anti-tTG IgA developed mild gastrointestinal symptoms or growth retardation and had histological findings typical of CD. CONCLUSIONS: The prevalence of anti-tTG IgA positivity among T1DM children was 8.6% and its occurrence was associated with younger age and short diabetes duration. Since CD presents in T1DM patients asymptomatically or with non-specific symptoms, periodic autoantibody screening is necessary for its early diagnosis.

Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). AIMS: We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD). MATERIALS AND METHODS: We studied 144 children and adolescents with T1DM. Their age was 12.3 +/- 4.6 (mean +/- SD) years, and duration of diabetes was 4.6 +/- 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay. RESULTS: The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 microIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09-1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7-2350.3), and 3) older age (OR 22.9, 95% CI 1.13-463.2). CONCLUSIONS: Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.

Thyroid function in children with epilepsy treated with sodium valproate monotherapy: a prospective study.

OBJECTIVE: Studies on the effects of sodium valproate (VPA) on thyroid hormone balance in patients with epilepsy are conflicting. The aim of this study was to prospectively evaluate the changes in thyroid profile in children with epilepsy treated with VPA monotherapy. METHODS: Serum thyroxine, free thyroxine, triiodothyronine, and thyrotropin (TSH) levels were evaluated in 30 children with epilepsy, before and at 6, 12, and 24 months of VPA monotherapy. RESULTS: All children had normal thyroid function before the initiation of VPA treatment. Serum VPA concentrations remained within the therapeutic range (50-100 mg/L) during the period of study. Thyroxine and free thyroxine levels were significantly decreased, whereas TSH levels were significantly increased at 6, 12, and 24 months of VPA therapy. Triiodothyronine levels were significantly decreased only at 24 months of therapy. Thirteen children (43.3%) at 6 months, 14 children (46.6%) at 12 months, and 15 children (50%) at 24 months of treatment had TSH values greater than 5 mIU/mL. Normal serum TSH levels were restored in all 8 children examined at 3 months after withdrawal of medication. CONCLUSIONS: Valproate monotherapy may cause significant alteration in thyroid profile in children with epilepsy, occurring early in the course of treatment and persisting as long as VPA is initiated. Therefore, it may be useful to measure serum thyroid hormone concentrations routinely in children with epilepsy taking VPA. Further prospective studies are required to determine the mechanisms and risk factors for development of thyroid disturbance in children treated with VPA monotherapy.

Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease.

BACKGROUND: Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. OBJECTIVE: To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. SUBJECTS AND METHODS: Thirty-four children with AITD, aged 9.62 +/- 2.35 years, and 31 matched controls, aged 9.24 +/- 2.98 years, were studied. RESULTS: The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, P = 0.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, P = 0.024). No other statistically significant differences were observed in HSV-1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. CONCLUSIONS: EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.

Thyroid dysfunction associated with increased low-density lipoprotein cholesterol in epileptic children treated with carbamazepine monotherapy: a causal relationship?

OBJECTIVE: Lipid abnormalities and thyroid dysfunction have been reported in patients treated with antiepileptic drugs. The aim of this study was to evaluate prospectively the association between thyroid and lipid profile in children treated with carbamazepine (CBZ) monotherapy. MATERIALS AND METHODS: Thyroid function was evaluated in 18 epileptic children, previously reported with CBZ-induced changes in serum lipid profile, before and at 6, 12 and 24 months of CBZ monotherapy. RESULTS: All children had normal thyroid function before the initiation of CBZ treatment. During CBZ therapy thyroid dysfunction, with increased thyrotropin (TSH) and decreased thyroxine (T4), free thyroxine (FT4) and triiodothyronine (T3) was found, while, significant association was revealed between serum low-density lipoprotein cholesterol (LDL-C) and TSH levels at 6 (r=0.469; p=0.043) and 12 (r=0.730; p=0.001) months of treatment. CONCLUSION: Lipid abnormalities may be associated with thyroid hormone disturbance in children treated with CBZ monotherapy. Since thyroid dysfunction and hypercholesterolemia are both associated with a higher atherosclerotic risk special attention and further studies are needed in epileptic patients treated with CBZ monotherapy.

Activity of the growth hormone/insulin-like growth factor-I axis in critically ill children.

Critical illness has an important impact on the human endocrine system. Very few studies have been performed to elucidate the alterations of the GH/IGF-I axis in acutely ill children. The aim of this study was to investigate several parameters of this axis in children with trauma (TRA) and sepsis (SEP) requiring admission to the pediatric intensive care unit (PICU). A total of 16 children, ten with TRA and six with SEP (age 1-10 years) as well as 18 healthy children (CS) of similar age and gender were included in the study. Two children, one with TRA and one with SEP, died. Serum IGF-I and -II, IGFBP-1 and -3, and GH levels were measured on days 1, 3 and 7 after admission. GH levels were higher in the patients than in CS (p = 0.04), with no difference between TRA and SEP, and were elevated during PICU stay (p = 0.05). Serum IGF-I, -II and IGFBP-3 were lower in the patients than in CS (p = 0.03, 0.02 and 0.001, respectively) with a tendency to increase up to day 7. Finally, IGFBP-1 levels were similar in the patients and CS. These findings indicate that critically ill children are characterized by low levels of IGF-I and -II as well as IGFBP-3 accompanied by elevated levels of GH, probably reflecting the development of peripheral GH resistance. No significant differences were found between the different catabolic conditions, sepsis and trauma.