Autoimmune Thyroid Disease In Children Research Articles

Potential Role of Selected miRNAs in the Pathogenesis of Autoimmune Thyroid Diseases in Children and Adolescents.

Many epigenetic factors, including microRNAs, are involved in the process of changing gene expressions. Small non-coding RNA molecules, called miRNAs, are responsible for regulating gene translation by silencing or degrading target mRNAs. It is acknowledged that for many diseases, they may be novel diagnostic and prognostic biomarkers. Patients with autoimmune thyroid diseases are more likely to develop nodules in the thyroid tissue, and Hashimoto's thyroiditis and Graves' disease predispose patients to thyroid cancer. We evaluated the concentrations of microRNA molecules (miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p, miR-150-5p) in the blood of children with thyroid disorders. In addition, we wished to identify molecules whose change in concentration predisposes to the development of thyroid cancer. The aim of this study is to evaluate selected epigenetic elements by analyzing the levels of miR-15a-5p, miR-126-3p, miR-142-5p, miR-150-5p and miR-21-5p in the blood of pediatric patients with Graves' disease (n = 25), Hashimoto's thyroiditis (n = 26) and thyroid nodular disease (n = 20) compared to a control group of healthy children (n = 17). The study consists of groups of children and adolescents aged 10-18 years with autoimmune thyroid disease, with thyroid nodular disease compared to a control group. The miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p and miR-150-5p molecules were determined through an immunoenzymatic assay using BioVendor reagents. There is a statistically significant decrease in the expression of the miR-15a-5p in children with Graves' disease (21.61 vs. 50.22 amol/μL, p = 0.03) and in patients with thyroid nodular disease compared to controls (20.23 vs. 50.22 amol/μL, p = 0.04). Higher levels of the miR-142-5p molecule are found in patients with thyroid disease (with GD-3.8 vs. 3.14 amol/μL, p = 0.01; with HT-3.7 vs. 3.14 amol/μL, p = NS, with thyroid nodular disease-4.16 vs. 3.14 amol/μL, p = 0.04). Lower levels of miR-126-3p were noted in the GD group compared to the control group (7.09 vs. 7.24 amol/μL, p = 0.02). No statistically significant changes in the expressions of miR-150-5p and miR-21-5p molecules were observed in the study groups. 1. The overexpression of the miR-142-5p molecule occurs in children and adolescents with thyroid diseases. 2. Decreased blood levels of miR-15a-5p predispose patients to the formation of focal lesions in the thyroid gland. 3. Identifying a lower expression of the miR-126-3p molecule in the blood of children with GD requires careful follow-up for the development of focal lesions in the thyroid gland and evaluation for their potential malignancy.

Associated autoimmune thyroid diseases in children and adolescents with type one diabetes in Jordan.

To investigate the prevalence of thyroid autoimmunity and related thyroid disorders among children and adolescents with type 1 diabetes in Jordan. In a retrospective study, thyroid stimulating hormone and thyroid hormone (Free T4) levels were measured in 684 children with type 1 diabetes who presented to Jordan University Hospital between January 2012 and February 2021. Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TGAb) antibodies were measured in 526 and 438 subjects with type 1 diabetes, respectively. 681 children were included in the study (52.4 % females, average current age 14.3 years, average age at diagnosis 8.0 years, and average diabetes duration 6.2 years). Of the whole group, 18 children (2.6 %) were diagnosed with subclinical hypothyroidism and 31 children (4.4 %) had overt hypothyroidism. Of those who were tested for TPOAb and TGAb, 22.6 and 23.1 % were positive respectively. Predictors for developing hypothyroidism were female sex and positive antibodies to glutamic acid decarboxylase. Screening for associated thyroid autoimmunity in children and adolescents with type one diabetes from Jordan is advised with a special focus on females and those with positive antibodies to glutamic acid decarboxylase.

Impact of iodine intake on the pathogenesis of autoimmune thyroid disease in children and adults.

Thyroid hormone (TH) regulates the body's metabolism and iodine, a vital trace mineral, is vital for TH synthesis. As a TH biosynthesis catalyst, iodine has a substantial role in our health. When there is a modest iodine deficit, the thyroid gland grows autonomously, resulting in thyrotoxicosis. Those who consume excessive iodine risk developing hypothyroidism and thyroid autoimmunity. A transient hyperthyroid condition may rapidly increase iodine consumption. Iodine deficiency is common across the globe, and provision of supplementary iodine, in forms such as iodized salt or vegetable oil, has many benefits. Vegetarians, for instance, may not consume adequate amounts of iodine in some countries with high iodine content. Reduced dietary iodine intakes may be a consequence of efforts to reduce salt intakes to prevent hypertension. In addition, iodine consumption is decreasing in many countries, even among those where endemic goiter has previously been eradicated, leading to the re-emergence of iodine-deficiency-related disorders such as goiter. This review will discuss how iodine can contribute to the development of thyroid disease.

RF14 | PSAT114 Conversion from one side of the autoimmune thyroid spectrum to the other: a pediatric clinical challenge

Abstract Introduction Graves disease and Hashimoto thyroiditis represent the two ends of the autoimmune thyroid spectrum. Spontaneous conversion from one to the other is a rare phenomenon, especially in children, and the underlying mechanism is unknown. Changes in the predominance of stimulating versus blocking TSH receptor antibodies (TRAb) has been proposed as a potential etiology.Method: We describe a series of cases of autoimmune thyroid disease in children that converted from one end of the biochemical spectrum to the other Result: Eleven patients of whom 55% were girls and 36% had Down syndrome (DS) were identified. Five (46%) presented with hyperthyroidism (hyper) that spontaneously converted to hypothyroidism (hypo). Four patients (36%) had hypo which converted to hyper while the remaining 2 (18%) presented with Hashitoxicosis (HT) with negative TRAb titers which later converted to hyper. In those who went from hyper to hypo, mean duration of antithyroid drug therapy was 1.8 ± 1.4 years and mean age at initial presentation was 11.0 ± 4.8 years (5-16). Before conversion, all 5 patients had positive TRAb titers with mean of 15.0 ± 4.2 and a mean thyroid peroxidase antibody level of 287.5 ± 389. A period of euthyroidism lasting 2.0 ± 0.8 years was present prior to the development of hypo with a mean TSH of 17.0 ± 25 mU/L (5.8-62). Mean duration of hypo in the second group was 5.0 ± 5.2 years and mean age at initial diagnosis was 6.7 ± 2.8 years (3-10). TSH became suppressed in all 4 patients, TRAb was elevated, and mean free T4 off levothyroxine was 3.3 ± 1.2 ng/dL (2.4-4.6). The two patients with initial HT were 12 ± 2.8 years at diagnosis and converted to hyper after 6.5 ± 0.7 months. Initial mean free T4 was 1.3 ± 0.2 ng/dL and after conversion was 4.6 ± 0.4 ng/dL along with strongly positive TRAb titers (mean of 6.9 ± 6.5). TSH became further suppressed after conversion to hyper (<0.01). More of our patients with DS converted from hypo to hyper than the other direction (75% vs 20%, p=0.01). However, two of them proceeded to have a wavering course between hyper and hypo requiring intensive monitoring and frequent changes in management. Conclusion Although oscillating thyroid function in children with autoimmune thyroid disease is uncommon, it is important for parents and providers to be aware of this entity. The natural history of these cases is extremely variable and clinical management is challenging. Our findings suggest that DS may be a risk factor for the phenomenon of vacillating thyroid function in pediatric patients. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m.

Association between atopic dermatitis and thyroid disease among U.S. adults in the 2001-2006 National Health and Nutrition Examination Survey

To the Editor: Atopic dermatitis (AD) is a common and chronic inflammatory dermatological condition that affects the daily life of individuals in various ways. Many studies have discussed the numerous autoimmune conditions that are potentially associated with AD. 1 Lu Z. Zeng N. Cheng Y. et al. Atopic dermatitis and risk of autoimmune diseases: a systematic review and meta-analysis. Allergy Asthma Clin Immunol. 2021; 17: 96https://doi.org/10.1186/s13223-021-00597-4 Crossref PubMed Scopus (6) Google Scholar Recent research has suggested that the underlying pathophysiology of AD may contribute to the development of autoimmunity. 2 de Lusignan S. Alexander H. Broderick C. et al. Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study. J Allergy Clin Immunol. 2022; 150: 709-713https://doi.org/10.1016/j.jaci.2022.03.030 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In addition, our group has reported that psoriasis is associated with thyroid dysfunction. 3 Liu J. Thatiparthi A. Martin A. et al. Association between psoriasis and thyroid dysfunction among US adults in the 2009-2014 National Health and Nutrition Examination Survey. J Am Acad Dermatol. 2022; 86: 897-899https://doi.org/10.1016/j.jaad.2021.03.030 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In 2012, Pedullà et al 4 Pedullà M. Miraglia Del Giudice M. Fierro V. et al. Atopy as a risk factor for thyroid autoimmunity in children. J Biol Regul Homeost Agents. 2012; 26: S9-S14https://doi.org/10.1111/jdv.12281 Crossref PubMed Scopus (21) Google Scholar reported a significant association between AD and autoimmune thyroid disease in children from Naples, Italy. However, there is limited research directly exploring the relationship between AD and thyroid disease in a large U.S. adult population. Our study focused on analyzing the relationship between AD and thyroid dysfunction in U.S. adults (ages 20-59 years) using the 2001-2006 National Health and Nutrition Examination Survey data, as this was the most recent National Health and Nutrition Examination Survey data available for AD. Institutional Review Board approval was not obtained as all patient data were de-identified.

Analysis of Thyroid Gland Problems with Shear Wave Elastography in Children with Celiac Disease.

The rate of autoimmune thyroiditis in children with celiac disease (CD) is high relative to the normal population. Since the majority of these patients are also euthyroid, thyroid imaging methods are gaining significance in diagnosis and follow-up. This study examines the effectiveness of thyroid ultrasonography (US) and thyroid shear wave elastography (SWE) in diagnosing thyroid disease in children with CD. This cross-sectional controlled study analyzed thyroid US, SWE, serum thyroid function tests, and thyroid autoimmune antibodies of 106 CD patients and 103 control patients without CD. An Aplio 500 ultrasound device with a linear array transducer and elastography software was used for thyroid US and SWE measurement of all patients. Right lobe thyroid volume, left lobe thyroid volume, total thyroid volume, thyroid mean elasticity (m/s), right lobe elasticity (kPa), left lobe elasticity (kPa), and mean thyroid elasticity (kPa) levels of the CD group were higher than those of the control group (p < 0.001). The relationships between thyroid US and thyroid mean elasticity (m/s), thyroid mean elasticity (kPa), anti-thyroid peroxidase antibody, and thyroid-stimulating hormone were positive and moderate, respectively (r = 0.612, 0.612, 0.636, and 0.565, respectively; p < 0.001). In this study, SWE findings were compatible with laboratory findings, as they constituted a sensitive and useful method in the diagnosis and follow-up of autoimmune thyroid disease in children with CD.

Autoimmune thyroid disease in children with diabetes and adolescents: A single center study from south Punjab.

To evaluate the prevalence of autoimmune thyroid disease in children with diabetes. The descriptive cross-sectional study was conducted from January to December 2019 at the Children Hospital and the Institute of Child Health, Multan, Pakistan, and comprised paediatric type 1 diabetes mellitus patients of both genders. Blood samples were obtained for detailed testing of thyroid functions tests. Data was analysed using SPSS 20. Of the 161 paediatric subjects, 83(51.6%) were boys. The overall mean age was 9.7±4.3 years. Thyroid peroxidase antibody was positive in 34(21.1%) patients and thyroglobulin antibody in 27(16.7%). Both antibodies were positive in 17(10.5%) patients. Six (3.7%) patients had evidence of subclinical hypothyroidism, 8(4.9%) had overt hypothyroidism and 1(0.62%) had hyperthyroidism. The prevalence of autoimmune thyroid disease among children and adolescents with type 1 diabetes mellitus was 21%, with hypothyroidism being more prevalent compared to hyperthyroidism.

Thyroid peroxidase antibodies are common in children with HLA-conferred susceptibility to type 1 diabetes, but are weakly associated with thyroid function.

Background The need for screening for autoimmune thyroid disease in children who have HLA-conferred susceptibility to type 1 diabetes (T1D), but have not yet been diagnosed with T1D, has not been thoroughly studied. The aim of this study was to describe the prevalence of positive thyroid peroxidase antibodies and its effect on thyroid function in children with genetic susceptibility to T1D as well as to describe the association between thyroid autoimmunity and HLA-DQ genotypes. Methods Cross-sectional study in 223 children (112 boys) aged 7.4-10.5 years with HLA-conferred susceptibility to T1D. TPOAb were measured in all children; thyroglobulin antibodies (TGAb) and thyroid function in TPOAb positive subjects. Results Girls had a significantly higher median TPOAb concentration than boys (12 vs 11 kU/L; p=0.001). Positive TPOAb occurred in 13.9% and positive TGAb in 4% of subjects. Only two children had mild changes in thyroid function. There was no association between HLA risk groups and the prevalence of TPOAb. Conclusions TPOAb are common in children with HLA-conferred susceptibility to T1D, yet are weakly associated with thyroid function, suggesting limited value of thyroid screening in this cohort.

Gender Differences at the Onset of Autoimmune Thyroid Diseases in Children and Adolescents.

Background: The incidence of autoimmune thyroid diseases (ATD) may vary with the beginning of reproductive function, although few reports differentiate the incidence before and during the onset of puberty, examining gender bias. We analyzed onset of ATD in a pediatric population to assess gender differences in onset age, disease subtype, pubertal status, autoimmune co-morbidity, family history and treatment, focusing on the interaction between gender and pubertal stage.Patients and methods: We retrospectively recorded 382 children and adolescents with ATD. In each patient physical examination was considered. The presence of other associated autoimmune diseases (AAD) and familial predisposition was also recorded.Results: Predominant prevalence was noted in females compared to males (p < 0.001), both in Hashimoto's diseases (HD or HT) and Graves' disease (GD) (p < 0.001). Mean age at diagnosis showed no significant difference between sexes (p > 0.05). A higher prevalence in pubertal subjects was noted compared to prepubertal (p < 0.001, particularly HT in early and GD in late pubertal stage), without sexes difference intra-(prepubertal vs. pubertal) and inter-puberty groups (prepubertal vs. early pubertal vs. late pubertal). Both in HT and in GD, the prevalence of autoimmune associated diseases (AAD) was higher in males compared to females (p = 0.04), with similar distribution according to the pubertal maturation. The familial predisposition was similarly distributed in both genders (p > 0.05) and into pubertal stages (p > 0.05).Conclusions: Females are more prone to develop ATD during puberty, earlier in HT than in GD. The effect of puberty is not different between genders, suggesting the role of additional factors other than hormones. The screening for detection of ATD is recommended in all patients with positive family history and other autoimmune diseases, mostly in males. Considerations of gender in pediatrics could be important to define pathogenic mechanisms of ATD and to help in early diagnosis and clinical management.

Analysis of chosen polymorphisms rs2476601 a/G – PTPN22, rs1990760 C/T – IFIH1, rs179247 a/G – TSHR in pathogenesis of autoimmune thyroid diseases in children

Background: Autoimmune thyroid diseases are multifactorial diseases with a genetic susceptibility and environmental factors. A potential role of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, the interferon-induced helicase domain 1 (IFIH1) gene, the thyroid-stimulating hormone receptor (TSHR) gene polymorphisms on autoimmune thyroid diseases (AITDs) in adults has been established unequivocally, but there is still lack of research articles including group of children.Objective and hypotheses: To estimate the association of polymorphisms of PTPN22, IFIH1 and TSH-R genes with the pre-disposition to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in children.Methods: The study was performed in 142 patients with GD, 57 with HT and 160 healthy volunteers. The three single-nucleotide polymorphisms (SNPs): rs2476601 – PTPN22, rs1990760 – IFIH1 and rs179247 – TSHR were genotyped by TaqMan SNP genotyping assay using the real-time PCR.Results: Rs2476601 A alleles were more frequent in patients with GD in comparison to healthy subjects (p = .009 with odds ratio [OR] = 2.13). Rs2476601 A alleles were more frequent in patients with HT in comparison to healthy subjects (p = .008, OR = 2.48). Rs1990760 T alleles were more frequent in male patients with GD in comparison to healthy males (p = .003, OR = 3.00). In case of HT patients, rs1990760 T alleles were also more frequent in males compared to healthy subjects (p = .086, OR =2.47). Rs179247 A alleles were more frequent in patients with GD in comparison to healthy subjects (p = 0.039, OR = 1.51).Conclusions: Rs2476601 A/G, Rs1990760 C/T and Rs179247 A/G polymorphisms could contribute to the development of AITDs in children. The main risk factor for rs2476601 and rs179247 is allele A. In case of rs1990760, the main risk factor is allele T.

Autoimmune Thyroid Disorder in Children and Adolescents with Type I Diabetes Mellitus

Background Type one diabetes mellitus (Type 1 DM) is the most common type of diabetes in children and adolescents, arising through a complex interaction of immune, genetic and environmental factors. Autoimmune thyroid disease is the most frequent disorder associated with Type one diabetes mellitus. This study aimed to evaluate incidence of autoimmune thyroid disease in children and adolescents with type I diabetes mellitus. Materials and Methods Cross sectional case control study was made on forty diabetic children with regular attending to the Endocrinology clinic and patients from pediatric ward in Al-Imamain Al-Kadhimain Medical City, Eraq, and forty healthy children matching in aged (1-15 years) and gender were taken as control. History taking, clinical examination, measurement of hemoglobin A1C, serum thyroid peroxidase autoantibodies and serum thyroid stimulating hormone levels were carried out. Serum thyroxine and triiodothyronine were measured. Results Serum thyroid peroxidase antibodies was positive in 15 % of diabetic patients, while it was negative in controls. In those with positive thyroid peroxidase antibodies 100% had subclinical hypothyroidism, 50% had hyperthyroidism. Risk of autoimmune thyroid disease was more in patients older than 5 years and it was neither related to the degree of control of diabetes nor to the duration, but it was more common in females. Conclusion There is higher incidence of autoimmune thyroid disease in children and adolescents with type one diabetes compared with normal children and this risk is not related to duration of diabetes, but it is more common in those older than 5 years. The risk of hypothyroidism is double the risk of hyperthyroidism in these patients.

Thyroid and Islet Autoantibodies Predict Autoimmune Thyroid Disease at Type 1 Diabetes Diagnosis.

Screening of autoimmune thyroid disease in children with type 1 diabetes is important but varies between clinics. To determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA-DQ at diagnosis of type 1 diabetes for autoimmune thyroid disease during follow-up. Forty-three Swedish pediatric endocrinology units. At diagnosis of type 1 diabetes, autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin, insulinoma-associated protein-2, and 3 variants of zinc transporter 8 (ZnT8W/R/QA) HLA-DQA1-B1 genotypes and thyroid function were analyzed in 2433 children. After 5.1 to 9.5 years, information on thyroxine treatment was gathered from the Swedish National Board of Health and Welfare's Prescribed Drug Register. Thyroxine was prescribed to 6% of patients. In patients <5 years of age, female sex [hazard ratio (HR) = 4.60; P = 0.008] and GADA (HR = 5.80; P = 0.02) were predictors. In patients 5 to 10 years old, TPOAb (HR = 20.56; P < 0.0001), TGAb (HR = 3.40; P = 0.006), and thyroid-stimulating hormone (TSH) (HR = 3.64; P < 0.001) were predictors, whereas in 10 to 15 year olds, TPOAb (HR = 17.00; P < 0.001) and TSH (HR = 4.11; P < 0.001) predicted thyroxine prescription. In addition to TPOAb and TSH, GADA at diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children <5 years of age.

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21–1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15–1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27–2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22–2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D’ = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.

Celiac Disease and Risk of Autoimmune Disorders: A Population-Based Matched Birth Cohort Study

To estimate the relative risk of developing type 1 diabetes mellitus (T1DM) and autoimmune thyroid disease in children with celiac disease (CD). A matched cohort design with linkage of administrative data was adopted. A total of 1215 cases of CD and 6075 references matched by sex and year of birth born in Friuli Venezia Giulia Region (Italy) between 1989 and 2011 were included. Cox regression models were used to estimate hazard ratios (HRs) for autoimmune diseases in patients with CD compared with references, stratified by sex and age at diagnosis. Individuals with CD had an increased risk of subsequent hypothyroidism (HR 4.64 [95% CI 2.88-7.46]) and T1DM (HR 2.50 [95% CI 0.94-6.66]), the latter not statistically significant. Risk of hypothyroidism was higher in males (HR 20.00; 95% CI 5.64-70.87) than females (HR 3.21; 95% CI 1.85-5.57) (P value<.01). No differences were observed between males and females risks for diabetes or age at CD diagnosis. The small number of hyperthyroidism cases identified precluded any statistical analysis. Children and youth with CD are at increased risk of developing autoimmune hypothyroidism and to some extent T1DM. This suggests the need for surveillance of children with CD in order to timely detect the onset of such comorbidities.

Association between thyroid autoimmunity and recurrent angioedema in children.

The association between thyroid autoimmunity (TA) and idiopathic isolated angioedema (or angioedema without urticaria) has not been evaluated in either children or in adults up until now. We, therefore, aimed to investigate underlying or concomitant TA and/or autoimmune thyroid disease in children diagnosed with recurrent idiopathic angioedema. Children who were consecutively diagnosed with recurrent idiopathic histaminergic acquired angioedema (IH-AAE) between January 2011 and January 2014 constituted the case group. A standard diagnostic and therapeutic algorithm was applied to all the patients with recurrent IH-AAE. Thyroid autoantibodies and thyroid function tests were measured in all the patients with recurrent IH-AAE and in healthy control groups. Prophylaxis with an antihistamine was started for patients with frequently recurrent IH-AAE. Eighty consecutive children with recurrent IH-AAE (49 boys; median age, 8.3 years) and 80 healthy children (39 boys; median, 8 years) were enrolled in this prospective, case-control study (p > 0.05 for age and sex). The IH-AAE group was significantly different than the control group with respect to TA (13.7% versus 2.5%, respectively; p = 0.009) but was similar with respect to autoimmune thyroid disease (3.7% versus 0%, respectively; p = 0.2). The median follow-up of the recurrent IH-AAE group was 34 months (range, 12-45 months). Patients with recurrent IH-AAE with and those without TA were not different with respect to either the need or the duration of antihistamine prophylaxis (p > 0.05 for both). Recurrent IH-AAE may be related to or associated with TA and/or autoimmune thyroid diseases in some children. However, exploring to see whether this association is a causal link or just an epiphenomenon deserves further investigation and longer follow-ups.

Do antithyroid antibodies affect hearing outcomes in patients with pediatric euthyroid Hashimoto's thyroiditis?

ObjectivesHashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease in children. HT is a multifaceted disease with a variable clinicopathological presentation, including hearing impairment. It is known that hearing function is negatively affected in patients with thyroid disorders. The literature includes a very limited number of studies on hearing function in euthyroid pediatric patients with HT. The aim of this study was to determine the relationship between cochlear function and HT, independent of thyroid function. Materials and MethodsThe study included 48 children and adolescents (42 females and 6 males) aged 9–18 years that were diagnosed as HT, and 30 gender- and age-matched healthy controls. Hearing was assessed via otoscopy, tympanometry, pure-tone audiometry, and measurement of distortion product otoacoustic emissions. ResultsThere weren't any significant differences in pure tone thresholds between the 2 groups based on pure-tone audiometry, except in the right ear at 6kHz and 8kHz. Distortion product otoacoustic emissions signal to noise ratios were significantly lower in the HT group than in the control group at 4 different frequencies (6kHz [left ear], 8kHz [left ear], 1.5kHz [right ear], and 6kHz [right ear]) (P<0.05). The signal to noise ratios at all frequencies were <6dB in 3% of left ears and 2.5% of right ears in the control group, versus 12.5% of left ears and 9.6% of right ears in the HT group. Distortion product amplitudes were significantly lower in the HT group than in the control group for both left and right ears at 1kHz, 1.5kHz, 3kHz, and 8kHz, and at 2kHz for left ears only (P<0.05). ConclusionsThe present findings show that cochlear function was lower in the HT group than in the control group. Accordingly, we think that hearing in patients with HT should be monitored periodically, even if their hearing thresholds are within normal limits. Thyroid autoimmunity appears to play an important role in a decrease in cochlear activity in pediatric HT patients.

Peculiarities of autoimmune thyroid diseases in children with Turner or Down syndrome: an overview.

Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies.Conclusions: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

The association between rs4684677 T/A polymorphism in preproghrelin gene and predisposition to autoimmune thyroid diseases in children

Background: A potential role of preproghrelin polymorphisms on autoimmune thyroid diseases (AITDs) has not been established equivocally yet. Aim: To estimate the association of two polymorphisms of preproghrelin gene with the predisposition to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in children. Methods: The study was performed in 145 patients with GD, 87 with HT and 161 healthy volunteers. The two single nucleotide polymorphisms (SNPs) rs696217 (C_3151003_20) and rs4684677 (C_25607748_10) in the preproghrelin gene were genotyped by TaqMan SNP genotyping assay using the real-time PCR. Results: Rs4684677 T alleles were more frequent in HT patients (99% in women and 100% in men) in comparison to healthy subjects (p = 0.002) with OR = 8.0 and 95% confidence interval for OR: 1.8–206.7. In women group, rs4684677 T alleles were more frequent compared to healthy controls (99%) in HT (p = 0.02) with OR = 6.7 and 95% confidence interval for OR: 1.2–168.37. Frequency of the SNP rs696217 did not differ between the groups. There was a significant relationship between rs696217 polymorphisms and anti-TSHR antibodies level (p = 0.036) in women from GD/HT groups. A significant relationship between rs696217 polymorphisms and anti-TG antibodies level in GD women group (p = 0.038) and between rs696217 polymorphisms and fT4 concentration (p = 0.03) were found. Conclusions: Rs4684677 T/A polymorphisms in preproghrelin gene could contribute to development of AITDs in children and T allele is the main risk factor.

Type 1 diabetes and autoimmunity.

.Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic β cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset.

Thyroid autoimmunity in children and adolescents with newly diagnosed type 1 diabetes mellitus.

PurposeThis study aim to investigate the occurrence of autoimmune thyroid disease in children and adolescents at onset of type 1 diabetes mellitus (T1DM) and to assess whether the presence of diabetes-specific autoantibodies can predict the autoimmune thyroid disorder.MethodsSeventy-three children with T1DM were recruited. Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulin autoantibodies (IAA), and thyroid antibodies were determined in all patients at the time of diagnosis.ResultsThe majority of patients (87.7%) had at least one pancreatic antibody (74.0% for GADA, 20.5% for ICA, and 24.7% for IAA). Thyroid autoantibodies were found in 19 of 73 patients (26.0%) at diagnosis. Thyroid autoimmunity (TA) incidence was not statistically significant by GADA or ICA positivity, but significantly higher by IAA positivity (P=0.03), and IAA positivity showed odds ratio, 4.931; 95% confidence interval, 1.323-18.381 for TA.ConclusionThe IAA positivity in children and adolescents with TIDM was strongly related to positivity of thyroid autoantibodies and thus it could serve as an index for early prediction of the development of the thyroid autoimmune disorder among children and adolescents with TIDM.