Thyroidectomy in children and adolescents: a systematic review.

Background: Thyroid surgery in pediatric population is not as common as that in adults, although they share the same indications, techniques and complications. This review aims to evaluate the surgical management of thyroid disease in patients under 18 years old. Methods: We conducted a bibliographic search in the international literature. Data from the identified studies such as demographics, indication for surgery, type of procedure, complications and length of hospital stay were recorded. A retrospective review study of all patients under 18 years old who underwent thyroidectomy was performed. Results: We included 37 retrospective studies and a total of 12,728 patients. Thyroidectomy was more common in female patients and the mean age was approximately 14 years old. The leading indication for surgery was benign thyroid pathology. Due to the surgical treatments' safety and effectiveness in young patients, total and subtotal thyroidectomy, whether for malignancies or benign diseases, is becoming more popular today. The most often occurring complication of pediatric thyroid surgery is hypoparathyroidism. Despite the high likelihood of recurrence of pediatric malignancies, overall survival rates of pediatric thyroid cancer are excellent. Conclusions: Thyroidectomy performed by high-volume thyroid surgeons in children and adolescents is considered an efficient and safe method of treatment of thyroid disease.

The Effect of Saffron Kozanis (Crocus sativus L.) Supplementation on Weight Management, Glycemic Markers and Lipid Profile in Adolescents with Obesity: A Double-Blinded Randomized Placebo-Controlled Trial.

Global rates of adolescent obesity have led the World Health Organization to consider the disease a pandemic that needs focus. In search of new anti-obesity agents, Crocus sativus, popularly known as saffron, is a nutraceutical agent, praised for its beneficial effects. The study aimed to investigate the possible effect of Kozanis saffron administration on weight management of obese prediabetic adolescents. Seventy-four obese prediabetic adolescents participated in a double-blind placebo-controlled trial of three arms, randomly assigned to receive either Kozanis saffron (n = 25, 60 mg/day), metformin (n = 25, 1000 mg/day) or a placebo (n = 24), for twelve weeks. Anthropometry, glycemic markers and lipid profiles were investigated at baseline and post-intervention. Saffron supplementation significantly reduced the weight z-score, BMI, BMI z-score and waist circumference (WC) of obese adolescents; however, this reduction was less significant compared to the effect of metformin. Metformin administration offered a significantly more profound improvement in anthropometry compared to saffron administration. Saffron administration also provided significant improvements in weight, weight z-scores, BMI values, BMI z-scores and WCs compared to the placebo. Saffron supplementation failed to change any glycemic marker, but provided a significant reduction in fasting triglyceride levels and also a significant increase in fasting HDL levels. Saffron Kozanis constitutes a promising nutraceutical option for adolescents and children with obesity and prediabetes in need of weight management.

Coexistence of Autoimmune Thyroiditis and Juvenile Idiopathic Arthritis.

PURPOSE: Autoimmune thyroid disease seems to occur more often in children with juvenile idiopathic arthritis (JIA) than in the general pediatric population. We investigated the prevalence of autoimmune thyroiditis (Hashimoto's thyroiditis) in young patients with JIA in Greece, which has not been evaluated previously. METHODS: This descriptive study included patients with JIA followed up at the Pediatric Rheumatology Unit of the Second Department of Pediatrics of a tertiary general hospital in Thessaloniki, Greece. All patients were diagnosed and sorted according to the classification criteria of the International League of Associations for Rheumatology. The presence of thyroid autoantibodies was considered for determining autoimmune thyroiditis. Basic demographic, clinical, and laboratory data were collected from patients' records.  Results: The analyzed sample comprised 130 patients with JIA (mean age 12.22 years; 69.2% female). Most patients (70%) had a family history of at least one autoimmune disease and 30.8% of Hashimoto's thyroiditis. More than half (53.8%) had enthesitis-related arthritis (ERA), 22.3% had oligoarthritis, and 15.4% had psoriatic arthritis. Thyroid autoantibodies were detected in 22/130 patients (16.9%) suggesting autoimmune thyroiditis; most of these patients were euthyroid, whereas 3/22 (13.6%) had overt hypothyroidism determined by elevated levels of thyroid-stimulating hormone, decreased levels of free thyroxine, and typical ultrasound findings for Hashimoto's thyroiditis. The prevalence of clinical cases of Hashimoto's disease was 2.3%. CONCLUSIONS: The prevalence of autoimmune thyroiditis in our JIA cohort is higher compared to the general population and consistent with the previously reported range. Hence, investigation for thyroid autoimmunity should be included in the workup of patients with JIA.

Methylation haplotypes of the insulin gene promoter in children and adolescents with type 1 diabetes: Can a dimensionality reduction approach predict the disease?

DNA methylation of cytosine-guanine sites (CpGs) is associated with type 1 diabetes (T1D). The sequence of methylated and non-methylated sites in a specific genetic region constitutes its methyl-haplotype. The aim of the present study was to identify insulin gene promoter (IGP) methyl-haplotypes among children and adolescents with T1D and suggest a predictive model for the discrimination of cases and controls according to methyl-haplotypes. A total of 40 individuals (20 T1D) participated. The IGP region from peripheral whole blood DNA of 40 participants (20 T1D) was sequenced using next-generation sequencing, sequences were read using FASTQ files and methylation status was calculated by python-based pipeline for targeted deep bisulfite sequenced amplicons (ampliMethProfiler). Methylation profile at 10 CpG sites proximal to transcription start site of the IGP was recorded and coded as 0 for unmethylation or 1 for methylation. A single read could result in '1111111111' methyl-haplotype (all methylated), '000000000' methyl-haplotype (all unmethylated) or any other combination. Principal component analysis was applied to the generated methyl-haplotypes for dimensionality reduction, and the first three principal components were employed as features with five different classifiers (random forest, decision tree, logistic regression, Naive Bayes, support vector machine). Naive Bayes was the best-performing classifier, with 0.9 accuracy. Predictive models were evaluated using receiver operating characteristics (AUC 0.96). Methyl-haplotypes '1111111111', '1111111011', '1110111111', '1111101111' and '1110101111' were revealed to be the most significantly associated with T1D according to the dimensionality reduction method. Methylation-based biomarkers such as IGP methyl-haplotypes could serve to identify individuals at high risk for T1D.

Predictive Factors for Pediatric Craniopharyngioma Recurrence: An Extensive Narrative Review.

Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis.

The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, p = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Diagnosis and Management of Endocrine Hypertension in Children and Adolescents.

Hypertension in childhood and adolescence has increased in prevalence. Interest in the disease was raised after the 2017 clinical practice guidelines of the American Academy of Paediatrics on the definition and classification of paediatric hypertension. Among the secondary causes of paediatric hypertension, endocrine causes are relatively rare but important due to their unique treatment options. Excess of catecholamine, glucocorticoids and mineralocorticoids, congenital adrenal hyperplasia, hyperaldosteronism, hyperthyroidism and other rare syndromes with specific genetic defects are endocrine disorders leading to paediatric and adolescent hypertension. Adipose tissue is currently considered the major endocrine gland. Obesity-related hypertension constitutes a distinct clinical entity leading to an endocrine disorder. The dramatic increase in the rates of obesity during childhood has resulted in a rise in obesity-related hypertension among children, leading to increased cardiovascular risk and associated increased morbidity and mortality. This review presents an overview of pathophysiology and diagnosis of hypertension resulting from hormonal excess, as well as obesity-related hypertension during childhood and adolescence, with a special focus on management.

Insulin gene promoter methylation status in Greek children and adolescents with Type 1 Diabetes.

The insulin (INS) gene is the one of the most important genes involved in the pathogenesis of Type 1 Diabetes (T1D) after the Major Histocompatibility Complex genes. Studies addressing the issue of hyper- or hypo-methylation status of the INS gene promoter have reported inconsistent results. The majority of studies showed hypomethylation; however a few studies have shown hypermethylation at specific cytosine-guanosine (CpG) sites in the promoter region of the INS gene. The aim of the present study was to analyze the methylation status of the promoter region of the INS gene in Greek children and adolescents with T1D. A total of 20 T1D participants (mean diabetes duration of 6.15±4.12 years) and 20 age- and sex-matched controls were enrolled in the present study. DNA was isolated from whole blood samples, modified using sodium bisulfite and analyzed using PCR and electrophoresis. DNA was then pooled with highly reactive supermagnetic beads at similar molar quantities, submitted for library construction and finally sequenced using next-generation sequencing. The methylation profile at 10 CpG sites around the transcription start site (TSS) of the INS promoter was analysed and expressed as the mean ± standard deviation. The overall mean methylation in patients with T1D did not differ compared with the healthy controls. There was a statistically significant difference between the two groups in hypermethylation at position -345 (P=0.02), while a trend (P=0.06) at position -102 was observed. According to the results of the present study, increased methylation in the INS gene promoter at specific CpG sites around the TSS were already present in childhood T1D. These data may possibly serve as a guide towards the identification of a methylation pattern for detection of development of T1D in genetically predisposed children.

Permanent damage of the sciatic nerve in an 8-year-old girl with newly diagnosed type 1 diabetes.

Neuropathy, a complication of type 1 diabetes (T1D), is a heterogeneous group, and chronic polyneuropathy is the most common form in adults. Αn 8-year-old girl admitted with severe diabetic ketoacidosis was diagnosed with T1D. She was managed with intravenous fluids and insulin and was subsequently commenced on multiple daily subcutaneous injections of insulin. On the 7th day of hospitalisation, a right foot drop with sensory loss on the dorsal surface and cellulitis were detected and the latter responded to intravenous antibiotics. Electrophysiology demonstrated reduced nerve conduction velocity indicative of severe axonal damage of the sciatic nerve (SN). Physiotherapy along with vitamins B6 and B12 and magnesium were prescribed. Twelve months later there was no sign of clinical improvement and the selective damage of the SN was deemed to be permanent. Peripheral neuropathy can occur in children with newly diagnosed T1D.Abbreviations: DKA: diabetic ketoacidosis; DN: diabetic neuropathy; HbA1c: glycated haemoglobin; MRC: Medical Research Council; MRI: magnetic resonance imaging; PICU: paediatric intensive care unit; SN: sciatic nerve; T1D: type 1 diabetes.

Beyond an Obvious Cause of Cholestasis in a Toddler: Compound Heterozygosity for ABCB11 Mutations.

A 27-month-old girl presented with a short history of jaundice initially attributed to drug-induced liver injury. During the preceding 20 days, she had received a 10-day course of cefprozil and 2 doses of a homeopathic preparation of cantharidin for cystitis. Severe conjugated hyperbilirubinemia was present with normal γ-glutamyl transpeptidase activity. Liver biopsy revealed marked canalicular and hepatocellular cholestasis, with moderate hepatocellular disarray, as well as evidence of chronicity, including moderate portal-tract and perisinusoidal fibrosis. Immunohistochemical studies revealed that bile salt export pump expression was preserved, whereas canalicular γ-glutamyl transpeptidase expression was largely absent. An inherited cholestatic disorder was suspected. The entire coding region of ABCB11, encoding bile salt export pump, was analyzed. The patient was found to be a compound heterozygote for the missense mutation c.3148C>T (p.Arg1050Cys) associated with benign recurrent intrahepatic cholestasis type 2 in the homozygous state and for the nonsense mutation c.3904G>T (p.Glu1302Ter) associated with progressive familial intrahepatic cholestasis type 2. Despite initial improvement with ursodeoxycholic acid, over the course of 5 years the patient developed cirrhosis that required liver transplant. Our report emphasizes the need for molecular studies even in patients with putatively "explained" cholestasis to reveal the entire spectrum of inherited cholestatic disorders.

Osteoprotegerin increases parallel to insulin resistance in obese adolescents.

Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). MATERIAL AND METHODS: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. RESULTS: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. CONCLUSIONS: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.

l-selenomethionine supplementation in children and adolescents with autoimmune thyroiditis: A randomized double-blind placebo-controlled clinical trial.

WHAT IS KNOWN AND OBJECTIVE: Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 µg daily as l-selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT. METHODS: Seventy-one (71) children and adolescents, with a mean age of 11.3 ± 0.3 years (range 4.5-17.8), diagnosed with AT (antibodies against thyroid peroxidase [anti-TPO] and/or thyroglobulin [anti-Tg] ≥60 IU/mL, euthyroidism or treated hypothyroidism and goitre in thyroid gland ultrasonography) were randomized to receive 200 µg l-selenomethionine or placebo daily for 6 months. Blood samples were drawn for measurement of serum fT4, TSH, anti-TPO and anti-Tg levels, and thyroid gland ultrasonography was performed at the entry to the study and after 6 months of treatment. RESULTS AND DISCUSSION: At the end of the study, a statistically significantly higher reduction in anti-Tg levels was observed in the Se group compared to the placebo group (Δ: -70.9 ± 22.1 vs -6.7 ± 60.6 IU/mL, P = 0.021). Although anti-TPO levels were also decreased in the Se group, this change was not statistically different from that of the control group (Δ: -116.2 ± 68.4 vs +262.8 ± 255.5 IU/mL, P = 0.219). No significant difference in thyroid gland volume was observed between the two study groups (P > 0.05). WHAT IS NEW AND CONCLUSION: In this original study, organic Se supplementation appears to reduce anti-Tg levels in children and adolescents with AT.

Testicular microlithiasis in a boy with X-linked adrenal hypoplasia congenita.

X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up.

Seasonality of month of birth in children and adolescents with autoimmune thyroiditis: a continuing conundrum.

Background The aim of this study was to analyze the seasonal birth month pattern in young patients with autoimmune thyroiditis and compare it with youth controls. Methods Medical records of a total of 298 children and adolescents of Greek origin, with a diagnosis of Hashimoto thyroiditis (HT) before the age of 21 years that were born from 1987 to 2010 were retrospectively reviewed. In addition, 298 consecutive subjects that were born from 1988 to 2012 and evaluated in a tertiary unit for any reason, served as controls, provided that they had no personal or family history of thyroid or any other autoimmune disease. Results Significant differences were found between children and adolescents with HT and healthy controls in the yearly pattern of month of birth distribution (p=0.029). During month-by-month analysis, it was shown that the highest and lowest predispositions to HT were among those born in spring (March) (odds ratio [OR] 2.34, p=0.005), and autumn (November) (OR 0.49, p=0.035), respectively. A binary logistic regression model also revealed that season of birth and sex were the only factors that remained related to HT disease, even after adjustment for confounding factors such as year of birth and age (p<0.001, Nagelkerke r-square 0.151). Conclusions This study suggests that the effect of certain seasonal factors during fetal development, reflected by the seasonal differences in birth pattern, in children and adolescents with autoimmune thyroiditis could contribute to long-term programming of an autoimmune response against the thyroid gland. Further studies are needed to demonstrate a clear cause and effect relationship between month of birth and HT.

Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes.

BACKGROUND: The association of selective immunoglobulin A (IgA) deficiency with type 1 diabetes (T1D) remains unclear. This study was to evaluate serum IgA concentrations in Greek children and adolescents with T1D. METHODS: In two hundred individuals with T1D, serum IgA concentrations were quantitatively determined using nephelometry. RESULTS: Immunoglobulin A deficiency was detected in 6 (3.0%) of 200 patients who were subjected to immunological evaluation. Recurrent infections were not recorded, but human papilloma virus infection was clinically suspected and confirmed by laboratory examination in a 5-year-old girl. In regard to coincidence of selective IgA deficiency with autoimmune diseases, celiac disease was detected in a girl and juvenile idiopathic arthritis in a boy. Serum IgA concentrations differed significantly when patients were grouped according to age at the beginning of the study (P<0.001), age at diagnosis of T1D (P=0.015) and coincidence of celiac disease (CD) (P=0.038). However, when the age of the patients was adjusted, difference in serum IgA concentrations was not statistically significant despite CD was present or not. Moreover, serum IgA concentrations were positively correlated with serum IgG (P<0.001) and IgE (P=0.001) concentrations and negatively correlated with serum antigliadin antibody IgG (P=0.035) concentrations. There was no association or correlation of serum IgA concentrations with glycemic control. CONCLUSION: The prevalence of selective IgA deficiency in Greek children and adolescents with T1D is high (3.0%). The correlation of serum IgA concentrations with serum IgG, IgE and anti-gliadin antibody IgG concentrations needs further investigation.

Suboptimal glycaemic control enhances the risk of impaired prothrombotic state in youths with type 1 diabetes mellitus.

OBJECTIVE: To estimate markers of prothrombotic state and endothelial dysfunction in youths with type 1 diabetes mellitus (T1DM) and investigate possible associations with anthropometric/demographic data, glycaemic control and lipid profile. METHODS: In a cross-sectional design, we recruited 155 youths with T1DM and determined levels of plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids and glycosylated haemoglobin (HbA1c). RESULTS: Of all the participants, 76 (49%) had increased levels of at least one of prothrombotic factors. Suboptimal glycaemic control was associated with a worse lipid profile and an eightfold increased risk of elevated vWF-Ag levels. Higher vWF-Ag concentrations were also correlated with impaired lipid profile and increased HbA1c values, whereas PAI-1-Ag was positively correlated only with triglyceride levels. After adjustment for potential confounders, only HbA1c contributed independently to the variation in vWF-Ag levels. CONCLUSION: Impaired prothrombotic state and consequently endothelial dysfunction are present in youths with T1DM, representing a cumulative risk factor for future cardiovascular disease (CVD). Achievement and maintenance of euglycaemia and normolipidaemia are crucial to decelerate progress of this process.

The role of PTPN22 C1858T gene polymorphism in diabetes mellitus type 1: first evaluation in Greek children and adolescents.

Type 1 diabetes mellitus (T1DM) is an autoimmune multifactorial disease. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. PTPN22 C1858T polymorphism was associated with T1DM in populations of Caucasian origin. The aim of this study was the investigation for the first time of the association of PTPN22 C1858T polymorphism with T1DM in Greek population. We studied 130 children and adolescents with T1DM and 135 healthy individuals of Greek origin. The polymorphism was genotyped using polymerase chain reaction with restriction fragment length polymorphism. C1858T and T1858T genotypes as well as 1858T allele were found more frequently in patients (10.8% and 5.8%, resp.) than in healthy individuals (5.9% and 3.0%, resp.) but at non statistically significant level. There was no statistically significant association found with gender, age at diagnosis, severity of onset, history of Hashimoto thyroiditis or family history of T1DM. Increased frequency of 1858T allele in patients than in controls, implying a probable association, agrees with results of similar studies on other populations. The inability to find a statistically significant difference is probably due to the decreased frequency of minor allele in Greek population, indicating the need for a larger sample.

HLA-DQB1*05 association with Hashimoto's thyroiditis in children of Northern Greek origin.

In order to investigate HLA-DRB1 and HLADQB1 gene polymorphisms in Northern Greek pediatric population with Hashimoto's thyroiditis (HT), we analyzed the distribution of these alleles in 17 patients and in 181 healthy subjects using polymerase chain reaction. No significant association was detected between HT and alleles analyzed. However, HLA-DQB1*05 was significantly increased in patients with age of diagnosis > 10 years (87.5%) compared to those with age of diagnosis