Katarzyna Ziora

Clinical Relevance of Thyroid-Stimulating Autoantibodies in Pediatric Graves' Disease—A Multicenter Study

CONTEXT AND OBJECTIVEnThe incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves orbitopathy (GO) and without orbital disease.nnnDESIGNnWe conducted a cross-sectional retrospective study.nnnSETTINGnSera were collected in seven American and European academic referral centers and evaluated in a central laboratory. PATIENTS AND SAMPLES: A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied.nnnMAIN OUTCOME MEASURESnTSAbs were measured using a novel, chimeric TSHR bioassay and a cAMP response element-dependent luciferase. TSH binding-inhibitory Ig (TBII) and parameters of thyroid function were also determined.nnnRESULTSnIn 82 untreated children with GD, sensitivity, specificity, and positive and negative predictive values for TSAb and TBII were: 100 and 92.68% (P = .031), 100 and 100%, 100 and 100%, and 100 and 96.15%, respectively. TSAb and TBII were present in 147 (94%) and 138 (87.9%) of the 157 children with GD (P < .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P < .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P < .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P < .0001). No significant differences were noted for TBII between the two groups. After a 3-year (median) medical treatment, the decrease of TSAb levels was 69% in GD vs 20% in GD and GO (P < .001). All 31 samples of euthyroid children with GO were TSAb positive; in contrast, only 24 were TBII positive (P = .016). All children with Hashimotos thyroiditis, nonautoimmune hyperthyroidism, type 1 diabetes, and juvenile arthritis and the healthy controls were TSAb and TBII negative.nnnCONCLUSIONSnSerum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.

Analysis of chosen polymorphisms in FoxP3 gene in children and adolescents with autoimmune thyroid diseases

Abstract Introduction: Forkhead box P3 (Foxp3) is an important regulatory factor for the development and function of T regulatory (Treg) cells. Moreover, it has been established that deficiency of the Foxp3 gene in Treg cells suppresses their regulatory function leading to the development of autoimmune diseases especially autoimmune thyroid diseases. The aim of our study was to estimate the association of three polymorphism of FOXP3 gene with the predisposition to Graves disease (GD) and Hashimotos thyroiditis (HT) in children and adolescents. Materials and methods: The study was performed in the group consisting of 145 patients with GD (mean age, 16.5u2009±u20092 years), 87 patients with HT (mean age, 15.2u2009±u20092.2 years) sequentially recruited from the endocrinology outpatient clinic and 161 healthy volunteers (mean age, 16.3u2009±u20093 years). DNA was extracted from the peripheral blood leukocytes using a classical salting-out method. The three single nucleotide polymorphisms (SNPs) rs3761549 (−2383C/T), rs3761548 (−3279G/T) and rs3761547 (−3499T/C) in the FOXP3 gene were genotyped by TaqMan SNP genotyping assay using the real-time PCR method. The levels of thyroid hormones, TSH and anti-thyroid autoantibody were determined using chemiluminescence method. Results: In our study, rs3761549G/A genotype was more frequent in female patients with GD in comparison to healthy female (15% vs. 7%, pu2009=u20090.033) with ORu2009=u20092.15 and 95% confidence interval for OR: 1.07–4.63. We have also observed rs3761547T/C to be more frequent in females with GD in comparison to control females, and this difference was close to statistically important (13% vs. 7%, pu2009=u20090.066) with ORu2009=u20091.99 and 95% confidence interval for OR: 0.96–4.48. There were no significant differences in males in analyzed SNPs and in females with rs3761548 SNP. Conclusion: In conclusion, these results may suggest that rs3761549G/A polymorphism in Foxp3 gene could contribute to GD development in females.

Association between omentin-1, bone metabolism markers, and cytokines of the RANKL/RANK/OPG system in girls with anorexia nervosa

INTRODUCTIONnOmentin-1, secreted by visceral adipose tissue, has been indicated in the regulation of bone metabolism in girls with anorexia nervosa (AN). The aim of the study was to evaluate the relationship between omentin-1 and bone metabolism in girls with AN as well as the potential involvement of OPG and RANKL in this relationship.nnnMATERIAL AND METHODSnSerum omentin-1, OC, CTx, OPG, and sRANKL were determined by ELISA in 49 girls with AN and in 30 healthy controls, aged 13 to 17 years.nnnRESULTSnGirls with AN exhibited significant reduction in body weight, BMI, and Cole index as well as a significant increase in serum omentin-1 levels, compared to healthy participants. These changes were associated with a significant decrease in serum OC and CTx levels and a significant increase in OPG and sRANKL while the OC/CTx and OPG/sRANKL ratios were significantly decreased. BMI and the Cole index correlated negatively and significantly with omentin-1 levels, positively with CTx levels and the OC/CTx ratio in the control group (C), girls with AN, and all study participants (C + AN). Girls with AN showed a significant negative correlation between BMI, the Cole index, and OPG levels. The combined group (C + AN) showed a significant positive correlation between BMI, the Cole index, and the OPG/sRANKL ratio. Omentin-1 levels correlated negatively and significantly with OC and CTx levels as well as with the OC/CTx and OPG/sRANKL ratios in the C, AN, and C + AN groups.nnnCONCLUSIONSnThe relationship between omentin-1, bone markers, and the OC/CTx and OPG/sRANKL ratios observed in girls with AN indicates the involvement of this adipokine in the regulation of dynamic balance between bone formation and resorption processes. Omentin-1 might exert a negative effect on bone remodelling in girls with AN by inhibiting both bone formation and resorption. The OPG/sRANKL system plays an important role in the latter.

Arterial Hypertension and Progression of Chronic Kidney Disease in Children During 10-Year Ambulatory Observation

The aim of this study was the long-term retrospective analysis of chronic kidney disease (CKD) progression in children, especially with regard to the presence of hypertension (HTN). The average rate of progression of CKD was higher in patients with HTN than without HTN. Hypertension treatment requires multidrug schemes which need to be intensified with extended time of CKD duration.

TGF-β1, bone metabolism, osteoprotegerin, and soluble receptor activator of nuclear factor-kB ligand in girls with anorexia nervosa

INTRODUCTIONnNumerous investigations, and especially in vitro studies, indicate that TGF-β1 may act as an important regulator of bone remodelling. Thus, it could be expected that disturbances of this cytokine production observed by several researchers might play a role in the mechanism leading to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether 1) girls with AN exhibited a relationship between TGF-β1 and bone metabolism (as assessed based on serum OC and CTx concentrations) and 2) whether OPG and sRANKL might modify the possible relationship between TGF-β1 and bone metabolism.nnnMATERIAL AND METHODSnSerum concentrations of TGF-β, OC, CTx, OPG, and its soluble ligand sRANKL were determined by ELISA in 60 girls with AN and in 20 healthy controls (C). All study participants were aged 13 to 17 years.nnnRESULTSnBody weight, BMI, BMI-SDS and the Cole index, serum TGF-β1, OC, CTx, and the OPG/sRANKL ratio were significantly reduced, while OPG and sRANKL levels were significantly increased, in girls with AN compared to healthy participants. BMI and the Cole index correlated negatively and significantly with serum CTx and OPG (AN group) or CTx only (groups C and C + AN). Girls with AN showed a positive and significant correlation between the Cole index and serum TGF-β1. The combination group (C + AN) showed a positive and significant correlation between BMI, the Cole index, and the OPG/sRANKL ratio and TGF-β1 concentration, while TGF-β1 correlated positively and significantly with OC concentrations and the OPG/sRANKL ratio. The Cole index and BMI were identified to be significant and independent predictors of CTx (C, AN, and C+AN groups) and OPG (AN group); the Cole index, BMI, and TGF-β1 independently predicted the OPG/sRANKL ratio (C, AN, and C + AN groups); TGF-β1 was found to be an independent predictor of OC (C + AN group).nnnCONCLUSIONSnChanges in bone markers, OPG, and/or OPG/sRANKL ratio observed in girls with AN are associated with changes in serum TGF-β1 concentrations. TGF-β1 suppression in girls with AN might lead to disturbances in the relationship between bone metabolism and the OPG/sRANKL system, which, in turn, might compromise the mechanism compensating for bone remodelling disturbances. (Endokrynol Pol 2016; 67 (5): 493-500).

Vaspin and selected indices of bone status in girls with anorexia nervosa

INTRODUCTIONnIn vitro studies indicate that vaspin may act as a regulator of bone metabolism. The aim of the study was to evaluate the relationship between vaspin and bone metabolism in girls with anorexia nervosa (AN), as well as the potential involvement of OPG and RANKL in this relationship.nnnMATERIAL AND METHODSnSerum vaspin, OC, CTx, OPG, and sRANKL were determined by ELISA in 50 girls with AN and in 30 healthy controls aged 13 to 17 years.nnnRESULTSnGirls with AN exhibited significant reduction in body weight, BMI, and Cole index as well as a significant increase in serum level of vaspin compared to healthy participants. These changes were associated with a significant decrease in serum OC and CTx levels and a significant increase in OPG and sRANKL, while the OPG/sRANKL ratio was significantly decreased. BMI and Cole index correlated negatively and significantly with CTx levels in the control group (C), girls with AN, and all study participants (C+AN). Girls with AN showed a significant negative correlation between BMI, the Cole index, and OPG levels. The combination group (C+AN) showed a significant positive correlation between BMI, Cole index, and the OPG/sRANKL ratio. In this group of girls vaspin levels correlated positively and significantly with sRANKL and negatively with body weight, BMI, Cole index, and OPG/sRANKL ratio. Girls with AN showed a significant negative correlation between vaspin levels and the OPG/sRANKL ratio.nnnCONCLUSIONSnUndernourishment and associated deficit of adipose tissue may result in inadequate vaspin production and bone metabolism disorders in girls with AN. Vaspin acts as a coordinator of the dynamic balance between bone formation and resorption processes; its action is affected by the cytokines of the RANKL/RANK/OPG system. Changes in the relationships between vaspin, bone markers, OPG, and RANKL might contribute to the development of osteoporosis in girls with AN. (Endokrynol Pol 2016; 67 (6): 599-606).

Evaluation of adipocytokines in children with chronic kidney disease

INTRODUCTIONnAdipose tissue through the many secreted adipocytokines creates a highly active metabolic and endocrine organ. The evaluation of serum adipocytokine concentration in children with chronic kidney disease (CKD) could serve as a marker of cardio-vascular complication progression and an index of outcome in adulthood and after kidney transplantation.nnnMATERIAL AND METHODSnThe aim of the study was to evaluate simultaneously the serum concentrations of six different adipocytokines: adiponectin, apelin, chemerin, omentin, resistin, and vaspin, in 28 children with CKD stage 5 on haemodialysis and peritoneal dialysis.nnnRESULTSnThe concentration of apelin, omentin, and resistin in children with CKD was significantly higher and the concentration of vaspin, adiponectin, and chemerin was significantly lower than in the control group. After adjusting to body mass index (BMI), the same results were obtained. After adjusting to body surface area (BSA), the concentration of vaspin, adiponectin, and chemerin did not differ between children with CKD and the control group. In analysis of the correlation between serum total adipocytokine levels in children with CKD we found a negative relationship in pairs: omentin-apelin and omentin-vaspin, and positive in pairs: adiponectin-chemerin and adiponectin-resistin.nnnCONCLUSIONSnOur results show that changes in serum adipocytokines concentration are associated with the kidney dysfunction in CKD in children. Longitudinal studies on larger groups of paediatric cohorts would be helpful in investigating whether adipocytokines play a harmful role in the development of CKD and would enable further understanding of the risk factors for CKD progression.

Serum apelin-12 level is elevated in schoolchildren with atopic asthma.

BACKGROUNDnThere are limited data on the role of adipokines in atopic asthma.nnnAIMnTo determine serum level of apelin-12 (APE-12) in asthmatic children in relation to BMI and gender.nnnMETHODSnSerum APE-12 levels were measured using ELISA in 89 asthmatic children (61 boys and 28 girls, aged 7.0-17.0 years) and in 33 healthy children. Among examined asthmatics 59 (19 girls and 40 boys) had normal weight and 30 (9 girls and 21 boys) were obese.nnnRESULTSnThe mean serum levels of APE-12 were significantly (pxa0<xa00.001) higher both in obese (174.1xa0±xa05.9xa0pg/mL) and non-obese asthmatic children (171.0xa0±xa04.0xa0pg/mL) than in healthy children (130.6xa0±xa02.1xa0pg/mL), regardless of gender. No relationships between examined the adipokine level and asthma severity, spirometric parameters, degree of allergic sensitization, BMI, BMI-SDS were observed.nnnCONCLUSIONnIncreased serum level of APE-12 suggests that this adipokine may be implicated in the pathogenesis of childhood atopic asthma.

Evidence of a significant vitamin D deficiency among 9–13-year-old Polish children: results of a multicentre study

PurposeTo evaluate the extent to which the population of Polish preadolescents is vitamin D deficient and to assess seasonal variations in vitamin D status.Participants and methodsA total of 720 healthy children aged 9–13xa0years (409 girls, 311 boys) residing in 6 representative geographical locations in Poland were studied. A parental-assisted questionnaire provided data on nutritional habits, vitamin D supplements and sun exposure. Serum concentration of 25-hydroxyvitamin was determined twice, after the winter in March and after the summer in October.ResultsIn March, vitamin D deficiency (25–50xa0nmol/L) was found in 64%, and severe deficiency (<u200925xa0nmol/L) in 20.2% of children. In October, the deficiency and severe deficiency were still noticed in 25.9 and 0.1% of children, respectively. The mean serum concentration of 25-OHD was 52% higher in October (55.4u2009±u200914.0xa0nmol/L) than in March (36.4u2009±u200913.5xa0nmol/L), (pu2009<u20090.01). In children with 25-OHDu2009<u200950xa0nmol/L in March, their 25-OHD concentration increased by 64% through March to October (32.5u2009±u20098.2 vs. 53.2u2009±u20097.9xa0nmol/L, pu2009<u20090.01). An association was found between 25-OHD concentration and regular consumption of vitamin D supplements, cod-liver oil and fish.ConclusionsThe majority of preadolescent Polish boys and girls show vitamin D deficiency after the winter period, although a distinct amelioration over summertime is found in this age group. There is a need to implement effective prevention and intervention strategies in the management of vitamin D deficiency among schoolchildren in Poland, with the supplementation throughout the entire year.

Treatment of severe primary IGF-1 deficiency using rhIGF-1 preparation – first three years of Polish experience

INTRODUCTIONnThe objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population.nnnMATERIAL AND METHODSnTwenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below -3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 μg/kg bw twice a day and was subsequently increased to an average of 100 μg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured.nnnRESULTSnMecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients.nnnCONCLUSIONSnTreatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.