Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

BACKGROUND: Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. METHODS: Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. RESULTS: At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. CONCLUSIONS: This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland.

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.

Predicted health care profile after transition to adult care in Turner syndrome children-experience of single center.

Introduction: Turner Syndrome (TS) is caused by the complete or partial loss of one of the X chromosomes in all or some female cell lines. The variable genotypes are responsible for a large phenotypic diversity, nevertheless most studies emphasize a weak correlation between genotype and phenotype. The study aimed to assess the occurrence of defects and diseases depending on the karyotype in patients with TS and correlation with the predicted health care profile after the transition to adulthood. Materials and methods: 45 patients of the Department of Endocrinology and Pediatrics of the Medical University of Warsaw in 1990-2002 were analyzed. Girls were divided into 2 subgroups: "A", which included 16 patients with the karyotype 45,X, and "B", which included 29 girls with mosaic karyotypes. Based on the literature data, characteristic phenotypic features and the typical defects or diseases accompanying TS were selected, and the frequency of their occurrence was compared in both subgroups. Accordingly to this data, the predicted medical care profile was determined. Results: In our study, patients with complete monosomy of the X chromosome had more characteristic phenotypic features. They needed sex hormone replacement therapy more often and started to menstruate spontaneously much less frequently (only 18.18% in monosomy vs. 73.91% in mosaic patients, p = 0.006). In patients with monosomy, congenital defects of the circulatory system were found more often (46.67% vs. 30.77%). The diagnosis in patients with mosaic karyotype was more often delayed, therefore the optimal time of growth hormone therapy was shorter. In our study, the X isochromosome determined the higher prevalence of autoimmune thyroiditis (83.33% vs. 12.5%, p = 0.049). We didn't find a correlation between the type of karyotype and health care profile after the transition, most of the patients needed more than 2 specialists. Most often, they required: gynecologists, cardiologists, and orthopedics. Conclusions: After the transition from pediatric to adulthood, patients with TS need multidisciplinary care, but not all need the same kind of assistance. The phenotype and comorbidities determine the profile of patients' health care, however it wasn't directly related to the type of karyotype in our study.

The link between vitamin D, chemerin and metabolic profile in overweight and obese children - preliminary results.

Background: Vitamin D affects adipogenesis, oxidative stress, inflammation, secretion of adipocytokines, lipid metabolism and thermogenesis. Some researchers postulate that those effects could be exerted by the influence of vitamin D on chemerin levels. Aim of the study: We aimed to investigate if there is a link between serum 25-hydroksyvitamin D [25(OH)D], chemerin and metabolic profile in overweight and obese children before and after vitamin D supplementation. Material and methods: The prospective study included 65 overweight and obese children aged 9.08-17.5 years and 26 peers as a control. None of the patients in the study group had received vitamin D within the last twelve months before the study. Results: The study group had lower baseline 25(OH)D (p<0.001) and higher chemerin (p<0.001), triglycerides (TG, p<0.001), triglycerides/high density lipoprotein cholesterol (TG/HDL-C, p<0.001), C-reactive protein (CRP, p<0.05), fasting insulin (p<0.001), Homeostasis Model Assessment - Insulin Resistance (HOMA-IR, p<0.001), alanine aminotransferase (ALT, p<0.001) and uric acid (p<0.001) compared to the control group. Baseline vitamin D was related to fasting insulin (R=-0.29, p=0.021), HOMA-IR (R=-0.30, p=0.016), HDL-C (R=0.29, p=0.020) and uric acid (R=-0.28, p=0.037) in the study group. Baseline chemerin was related to insulin at 30' (R=0.27, p=0.030), 60' (R=0.27, p=0.033), 90' (R=0.26, p=0.037) and 120' (R=0.26, p=0.040) during the oral glucose tolerance test (OGTT) and ALT (R=0.25, p=0.041) in the study group. Correlation between vitamin D and chemerin (R=-0.39, p=0.046) was found only in the control group. After six months of vitamin D supplementation a decrease in CRP (p<0.01), total cholesterol (p<0.05), ALT (p<0.01), glucose at 150' OGTT (p<0.05) was observed. Moreover, we noticed a tendency for negative association between 25(OH)D and chemerin levels (p=0.085). Multivariable backward linear regression models were build using baseline vitamin D, baseline chemerin and six months chemerin as the dependent variables. Conclusions: Our study confirmed that vitamin D has positive effect on metabolic profile in overweight and obese children. The relationship between vitamin D and chemerin is not clear, nevertheless we have observed a tendency to decrease chemerin concentrations after improving vitamin D status, even without a significant reduction in body fat mass.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

Decreased level of soluble receptor activator of nuclear factor-κß ligand (sRANKL) in overweight and obese children.

Introduction: Childhood obesity contributes to the development of cardiovascular diseases. The molecular pathway - receptor activator of nuclear factor-κß ligand (RANKL), its receptor RANK and osteoprotegerin (OPG) - takes part not only in bone metabolism but is also involved in the atherosclerosis process. RANKL stimulates osteogenic differentiation and calcification of vascular smooth cells. The associations between the OPG-sRANKL system and various cardiovascular risk factors were displayed. We aimed to evaluate the relationships between serum sRANKL (soluble RANKL) levels and the OPG/sRANKL ratio with cardiometabolic risk factors in overweight and obese children. Material and methods: The study included 70 children with overweight and obesity (mean age 13.0 ± 2.8) and 35 age-matched normal weight, healthy peers as a control group. In all patients, anthropometric measurements and laboratory tests were performed. Additionally, an oral glucose tolerance test (OGTT) was made only in overweight and obese children. Atherogenic and insulin resistance indices were calculated. Results: Overweight and obese children had lower sRANKL levels compared to the control group (median 276.95 vs 325.90, p=0.011), and consequently a higher OPG/sRANKL ratio (0.02 vs 0.01, p = 0.013). The studied children in the lowest quartile of sRANKL levels had higher body weight, Body Mass Index, waist circumference and increased glucose and insulin levels 60 minutes after OGTT and higher uric acid values compared to children in the highest quartile. In multivariable linear regression analysis sRANKL negatively correlated only with uric acid (ß = - 0.508, p = 0.041). No association was found for the OPG/sRANKL ratio. Conclusion: Excess fat mass seems to alter the OPG/RANKL ratio mainly by reducing serum sRANKL levels. The correlation between sRANKL and uric acid may suggest a contribution of the OPG-sRANKL system in the cardiometabolic process, but that observation should be confirmed in future studies.

Changes of Peripheral Th17 Cells Subset in Overweight and Obese Children After Body Weight Reduction.

Background: Obesity has been a growing problem in young patients leading to serious metabolic complications. There are many studies supporting the idea, that obesity should be considered as a chronic inflammation closely associated with immune system alterations. Th17 subpopulation is strongly involved in this process. The aim of our study was to evaluate circulating Th17 cells in overweight and obese children and explore the relationships between Th17 subset and metabolic parameters. Methods: We evaluated peripheral Th17 cells in fresh peripheral blood samples from 27 overweight and obese and 15 normal-weight children. Th17 cells were identified by flow cytometry using monoclonal antibody and intracellular IL-17A staining. Th17 cells were defined as CD3+CD4+CD196+IL-17Aic+. The analysis involved anthropometric and metabolic parameters measured at baseline and three months after the change of lifestyle and diet. We evaluated the relationship between metabolic parameters and Th17 cells. Results: In overweight and obese children we found significantly higher Th17 cells percentage compared to normal weight controls (median 0.097% (0.044 - 0.289) vs 0.041% (0.023 - 0.099), p = 0.048). The percentage of Th17 cells decreased statistically significantly in children who reduced weight after the intervention (0.210% (0.143 - 0.315) vs 0.039% (0.028 - 0.106), p = 0.004). In this group we also noticed statistically significant reduction of TC and LDL-C concentration (p = 0.01, p = 0.04, respectively). Conclusions: Obesity in children is associated with increased percentage of peripheral Th17 cells. Weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be relatively easily reversible.

Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland.

Short stature resulting from SGA is an obligatory indication for treatment with rhGH. The aim of the study was to assess the response to rhGH treatment in patients treated in the years 2016−2020 in six clinical centers in Poland. During the analysis, auxological data were collected, and anthropometrical parameters (Ht, SDS Ht, HV and ΔHV) were reassessed. Subgroups of patients with dysmorphic features (DYSM), fetal alcohol syndrome (FAS) and Silver-Russel syndrome (SRS) were selected. The study group consisted of 235 children (137 boys). The medium initial age was 9.08 years, and 190 patients were in the prepubertal stage. The poor response to treatment was defined as ΔHt SDS < 0.3 and/or ΔHV < 3 cm/year. Seventeen per cent of all patients after the first year and 44% after the second year met the ΔHt SDS < 0.3 criterion, and 56% during the first and 73% during the second year met the ΔHV < 3 cm/year criterion. Our data suggest that patients with SRS may show the best response to treatment, which was sustained throughout the follow-up period. The best response in all subgroups was observed during the first 12 months of therapy. Although the proportion of patients meeting the poor response criteria was high, only a few patients exceeded the 97th percentile for IGF-1 concentration during the first year of treatment. This might suggest that increasing the dose of rhGH in the second treatment year in order to sustain accelerated HV would be safe in these patients.

Vitamin D Effects on Selected Anti-Inflammatory and Pro-Inflammatory Markers of Obesity-Related Chronic Inflammation.

Background: Obesity is related to changes in adipokine secretion, activity of adipose tissue macrophages, helper T cells, and regulatory T cells. It has been confirmed that vitamin D has potent anti-inflammatory properties. It contributes to reduction in pro-inflammatory mediators and an increase in anti-inflammatory cytokines. There is also evidence that vitamin D could decrease C-reactive protein (CRP) and affect selected haematological indices. Aim of the Study: We aimed to evaluate the effect of vitamin D on interleukin (IL)-10, IL-17, CRP, blood leukocyte profile, and platelet (PLT) count in overweight and obese children before and after six months of vitamin D supplementation. Material and Methods: The study group consisted of 67 overweight and obese children aged 9.08-17.5 years. The control group included 31 normal weight peers age- and sex-matched. None of the studied children had received vitamin D supplementation before the study. Data were analyzed at baseline and after vitamin D supplementation. Results: The study group had lower baseline 25(OH)D (p<0.001) and higher white blood cell (WBC) (p=0.014), granulocyte (p=0.015), monocyte (p=0.009) and CRP (p=0.002) compared to the control group. In the study group, vitamin D levels were related negatively to nutritional status. Leukocyte profile parameters, PLT, CRP, IL-10 or IL-17 were not related to baseline 25(OH)D. Baseline IL-17 levels correlated with monocytes (R= 0.36, p=0.003) independently on 25(OH)D deficit. In children with vitamin D <15ng/ml, the baseline 25(OH)D was related to CRP (R=-0.42, p=0.017). After six months of vitamin D supplementation, we noticed a decrease in CRP levels (p=0.0003). Serum 25(OH)D correlated with IL-10 in that period (R=0.27, p=0.028). Moreover, we noticed that IL-10 correlated with monocyte (R=-0.28, p=0.023). We did not find any significant associations between 25(OH)D and leukocyte profile parameters, PLT, or IL-17. The multivariable stepwise regression analysis identified IL-10 as the parameter positively associated with 25(OH)D. Conclusions: Our study confirmed beneficial effects of vitamin D supplementation in overweight and obese paediatric populations. Vitamin D intake seems to exert its anti-inflammatory effect mainly via decreasing the CRP level and protecting stabile values of IL-10, rather than its impact on pro-inflammatory factors such as lL-17 and leukocyte profile parameters.

Follow-Up of Thyroid Function in Children With Neonatal Hyperthyroidism.

Introduction: Neonatal hyperthyroidism mainly occurring in the children born to mothers with Graves' disease (GD). The influence of maternal GD on the newborn's thyroid function includes not only hyperthyroidism, but also various forms of hypothyroidism. Maternally transferred thyrotropin receptor antibodies (TRAb), the antithyroid drug (ATD) administration during pregnancy and previous definitive treatment of GD (radioactive iodine therapy or thyroidectomy) in the mother impact the function of the fetal/neonatal thyroid. Some newborns born to mothers with GD may present central hypothyroidism (CeH) due to impaired regulation of the fetal hypothalamic-pituitary-thyroid axis. The aim of this study was to evaluate different types of thyroid dysfunction in babies with neonatal hyperthyroidism. Materials and Methods: Medical records of 14 infants with neonatal hyperthyroidism (13 born to mothers with GD, and one born to mother with Hashimoto thyroiditis) were analyzed. Results: Transient hyperthyroidism was the main thyroid dysfunction in our study group. Overt hyperthyroidism with highly increased TRAb levels (mean 13.0 ± 7.0 IU/L) was diagnosed in 6 (43%) neonates. Another 6 (43%) babies presented hyperthyroidism with slightly increased fT4 and/or fT3 levels and TSH levels in the lower limit of the normal range coinciding with positive TRAb levels (mean 3.8 ± 1.6 IU/L). Normal thyroid hormone levels with TSH levels below the lower limit of the range were observed in 2 (14%) neonates. Four babies in the study group (28.5%) required further levothyroxine (L-T4) supplementation due to CeH or, in one case, due to primary hypothyroidism. Conclusion: Our study highlights the need for prolonged monitoring of thyroid function in children born to mothers with GD. Diagnosis of CeH could be delayed due to its masking by transient hyperthyroidism. Prolonged thyroid-stimulating hormone suppression after TRAb elimination should be considered as a signal announcing CeH.

Decreased Thyroxine Levels during rhGH Therapy in Children with Growth Hormone Deficiency.

BACKGROUND: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. METHODS: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. RESULTS: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. CONCLUSIONS: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy.

Thyroid Hormone Changes Related to Growth Hormone Therapy in Growth Hormone Deficient Patients.

The alterations in thyroid function during recombinant human growth hormone (rhGH) treatment have been reported by many authors since this therapy became widely available for patients with growth hormone deficiency (GHD). Decrease of thyroxine level is the most frequent observation in patients treated with rhGH. This paper presents literature data describing changes in thyroid function related to rhGH therapy and a current explanation of mechanisms involved in this phenomenon. The effect of GH on the hypothalamic-pituitary-thyroid (HPT) axis is dependent on a multilevel regulation beginning from influence on the central axis, thyroid, and extra-thyroidal deiodinases activity as well as the impact on thyroid hormone receptors on the end. Changes in central and peripheral regulation could overlap during rhGH therapy, resulting in central hypothyroidism or an isolated slight deficiency of thyroxine. The regular monitoring of thyroid function is recommended in patients treated with rhGH and the decision of levothyroxine (L-thyroxine) supplementation should be made in the clinical context, taking into account thyroid hormone levels, as well as the chance for satisfactory growth improvement.

Efficacy and safety of sirolimus therapy in familial hypoinsulinemic hypoglycemia caused by AKT2 mutation inherited from the mosaic father.

Activating mutation in the insulin signal-transducing kinase AKT2 results in severe hypoinsulinemic hypoketotic hypoglycemia and a characteristic phenotype of possible overgrowth and, sometimes, acanthosis nigricans. Herein, we describe a metabolic and hormonal profile before and during treatment with sirolimus in two brothers with AKT2 mutation inherited from the mosaic father, who showed low-level mosaicism in sperm. The boys, aged 1 and 14, who had severe non-insulin-dependent hypoketotic hypoglycemia and a typical dysmorphism, were admitted to endocrinology department for the analysis of their metabolic parameters: lipids, lactate, ammonia, glucose, insulin, c-peptide, and hormones (GH, IGF1, IGFBP3, TSH, fT4, cortisol, ACTH) before and during treatment with sirolimus. Previously, they had been treated with high-carbohydrate diet. The brothers were started on sirolimus with subsequent normalization of glycemia and reduced carbohydrate feedings overnight. The lowest fasting glucose levels improved from 20 mg/dl to 45 mg/dl in both sibs. The BMI of both brothers significantly dropped. After 6 months of sirolimus therapy we did not observe any laboratory or clinical side effects of the treatment.

Development of obesity from childhood to adolescents.

INTRODUCTION: Obesity is a major health problem in Poland and around the world. Excessive gain in early childhood is an important risk factor for the development of obesity. The aim of the study was to analyze the prevalence of obesity in 2-, 4- and 6-year-old obese children. MATERIAL AND METHODS: The study group: 656 overweight and obese children aged 5-18 years old. The patients' height and weight were measured, body mass index (BMI) was calculated. Overweight: BMI between 85th-97th percentile and obesity: BMI > 97th were defined using World Health Organization. BMI < +2 SDS as overweight, BMI ≥ +2 SDS as class I obesity, and BMI ≥ 3 SDS as class II. Measurements from the health books of children aged 2 (n = 626), 4 (n = 533) and 6 (n = 518) years old were analyzed. RESULTS: Mean age: 12.25 ±2.90 years, BMI SDS: +2.54 ±0.60. There were 100 overweight (15.2%) and 556 obese (84.8%) children in the group, including 143 patients with class II obesity (21.8%). Children < 10 years old comprised 28%. It was established that 36.6% of the patients were overweight or obese at the age of 2 years old. At the age of 4, the percentage was 73.9%, and at the age of 6, it was as high as 84%. CONCLUSIONS: 1. The children studied had excess body weight from early childhood. The prevalence of obesity increased with age. 2. Systematic monitoring of developmental parameters in children is essential from an early age.

Growth response and metabolic effects of growth hormone therapy in appropriate-for-gestational-age growth hormonedeficient children in relation to birth size and gestational age: A preliminary study.

The aim of the study was to investigate the influence of birth weight (BW), birth length (BL) and gestational age (GA) on growth pattern and metabolic profile in appropriate-for-gestational-age (AGA) growth hormone-deficient children before and during recombinant human growth hormone (rhGH) therapy. Forty children with isolated idiopathic growth hormone deficiency underwent auxological and biochemical assessment at baseline and after 6 and 12 months of rhGH therapy. Biochemical analysis included: insulin-like growth factor I (IGF-I), adiponectin, resistin, fasting glucose, fasting insulin, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and glycated haemoglobin (HbA1c). There was a tendency for positive association between BW and baseline height standard deviation score (SDS). GA correlated with baseline weight SDS (p=0.019) and BMI SDS (p=0.039). GA was associated with baseline fasting glucose (p=0.031), fasting insulin (p=0.027), HOMA-IR (p=0.010) and QUICKI (p=0.016). BW correlated with baseline HbA1c (p=0.032). After the initiation of rhGH therapy we did not find any significant relationships between birth size parameters or GA and metabolic profile of the studied children. In conclusion, our results suggest that AGA GH-deficient children born with higher birth size parameters and higher GA had better first-year growth response to rhGH therapy and better baseline metabolic profile, especially parameters of carbohydrate metabolism. In order to optimize the effects of rhGH therapy, higher rhGH doses should be considered in those GH-deficient children who were born with lower birth size and GA.

Chronic inflammation and the growth hormone/insulin-like growth factor-1 axis.

Interactions between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the immune system are complex, bidirectional, but not fully explained. Current reviews based on numerous studies have indicated that chronic inflammation could suppress the GH/IGF-1 axis via several mechanisms such as relative GH and/or IGF-1 insufficiency, peripheral resistance to GH and/or IGF-1 resulting from down-regulation of GH and IGF-1 receptors, disruption in the GH/IGF-1 signalling pathways, dysregulation of IGF binding proteins (IGFBPs), reduced IGF bioavailability, and modified gene regulation due to changes in the microRNA system. It is well-known that relationships between the immune system and the GH/IGF-1 axis are mutual and GH as well as IGF-1 could modulate inflammatory response and the activity of systemic inflammation. Available data indicate that the GH/IGF-1 axis exerts both pro-inflammatory and anti-inflammatory effects. Pro-inflammatory cytokines such as interleukin-6 (IL-6), tumour necrosis factor-a (TNF-α), and interleukin-1b (IL-b) are some of the most significant factors, besides malnutrition, chronic stress, and prolonged use of glucocorticoids, which impair the activity of the GH/IGF-1 axis, and consequently lead to growth retardation in children suffering from childhood-onset chronic inflammatory diseases. In this review, we discuss the mechanisms underlying the impact of chronic inflammation on the GH/IGF-1 axis and growth processes during childhood and adolescence, based on a number of experimental and human studies.

Changes in leukocyte profile and C-reactive protein concentration in overweight and obese adolescents after reduction of body weight.

AIM OF THE STUDY: To assess the changes in the leukocyte profile and C-reactive protein (CRP) concentration in adolescents with excess fat mass after 6-12 months of dietary intervention. MATERIAL AND METHODS: The retrospective study included 99 overweight and obese adolescents, aged from 10.0 to 17.5 years, 82 of whom were re-hospitalized 6 to 12 months after dietary counseling. The control group consisted of 42 normal weight peers. Anthropometric measurements and laboratory tests were performed, homeostasis model assessment - insulin resistance (HOMA-IR) and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio were calculated. RESULTS: Obese and overweight adolescents had higher white blood cells (WBC), neutrophil, monocyte counts and CRP concentration. In the backward stepwise regression analysis, body mass index standard deviation score (BMI SDS) and fasting insulin concentration were independent predictors of WBC and neutrophil counts at the baseline. At the follow-up visit in 45 (54.8%) children, who had lost weight, decreases in WBC, neutrophil and monocyte counts and CRP, fasting insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) concentrations were observed. Changes in WBC and neutrophil counts were dependent on changes in HOMA-IR and TG/HDL ratio. Changes in HOMA-IR had a significant impact on changes in the monocyte count. CONCLUSIONS: Adipose tissue promotes systemic inflammation and its intensity depends on the degree of obesity and insulin resistance. This state is reversible. Changes in HOMA-IR were independent predictors of changes in WBC, neutrophil and monocyte counts after reduction of body weight.

Peripheral blood picture and aminotransferase activity in children with newly diagnosed Graves' disease at baseline and after the initiation of antithyroid drug therapy.

AIM OF THE STUDY: Assessment of the peripheral blood picture and aminotransferase activity in children with newly diagnosed Graves' disease (GD) at baseline and 4-6 weeks after the initiation of antithyroid drug (ATD) therapy. MATERIAL AND METHODS: Data of 59 children were assessed retrospectively. Baseline analysis included concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), TSH receptor antibodies (TSH-R Ab), complete blood cell count (CBC), aspartate (AST) and alanine aminotransferase (ALT) activity. Reassessment of CBC and aminotransferase activity was performed 4-6 weeks after the initiation of ATD therapy. RESULTS: Significant decreases in the neutrophil count, MCV, haemoglobin (Hgb), red blood cell (RBC) count, white blood cell (WBC) count and platelet (PLT) count were found in 37.3%, 32.2%, 22%, 13.6%, 8.5% and 5% of untreated patients, respectively. Increased baseline ALT and AST activity was observed in 44% and 32.2% of children, respectively. Initiation of ATD therapy led to significant changes in Hgb, RBC and PLT count, RDW and ALT activity. Negative associations between TSH-R Ab, TSH and MCV were found. ALT and AST activity were negatively related to baseline TSH levels. ALT activity was also associated with baseline fT4 and fT3. CONCLUSIONS: The incidence of haematopoiesis and liver abnormalities in GD children seems to be similar to that reported in adult patients. The most common alterations are changes in neutrophil count, RBC parameters and ALT activity. The initiation of ATD therapy usually leads to significant improvement in those parameters.

Fructose Consumption and Lipid Metabolism in Obese Children and Adolescents.

Inappropriate dietary habits influence the development of excessive body weight. The role of added sugars, including fructose, notably is significant in this process. It is estimated that fructose intake has increased many times over the past two centuries. The aim of the study was to define the effect of fructose consumption on anthropometric indices and lipid metabolism in obese (body mass index (BMI) >30 kg/m2) children and adolescents. The study included 84 patients (47 girls and 37 boys) aged 7-18 years, divided into prepubertal, pubertal, and post-pubertal age groups. Aside from BMI, the assessment comprised waist circumference, body composition estimated with bioelectrical impedance (BIA), plasma lipid profile, fructose intake consumption based on a 3-day menu analysis, and a number of calculated atherogenic indices. The major findings were that total daily fructose intake was high, on average, ranging from 19 to 26 g, with no appreciable relation to age. A higher fructose intake from beverages is significantly associated with the percentage of body fat, waist circumference, waist-to-height ratio, and also with the content of total cholesterol, triglycerides, and the level of atherogenic indices. In conclusion, fructose appears a particularly unfavorable component in children's diet as it is conducive to visceral obesity and atherogenic lipid profile. However, inadequate proportions of other macronutrients may also be at play in the development of metabolic diet-related disorders.

Seasonal Variation in Month of Diagnosis of Polish Children with Type 1 Diabetes - A Multicenter Study.

AIM: The seasonal variation of incidence of type 1 diabetes (T1D) theory supports the hypothesis that environmental factors play a role in the onset of the disease. The aim of this study is to assess seasonality of month of diagnosis in children with T1D in Poland. MATERIAL AND METHODS: the study group consisted of 2174 children from eastern and central Poland diagnosed with T1D between 2010 and 2014. Analysis was performed in different age groups, based on place of residence (rural/urban area) and depending on sex. RESULTS: We noted significant seasonality in the incidence of T1D with a peak in diagnosis of diabetes in January and the minimum rate in June. A total of 423 (19%) children were diagnosed in the warmest months (June to August with a mean temperature of 16.8°C) compared to 636 (29%) recognised in the coldest months (December to February with a mean temperature of -1.6°C), OR 0.57 95%CI [0.51-0.67], p<0.0001. We noted a more flat seasonal pattern in children 0-4 years of age compared with subjects 5-17 years old with a week correlation of trend comparison between both groups, r=0.69, p=0.001. Similar seasonal variation in the incidence of T1D was noted in children from urban and rural setting. For girls, seasonal pattern peaks were observed one month earlier as compared to boys. CONCLUSIONS: Seasonal variation in incidence of T1D diagnosis of Polish children supports the role of different environmental factors in diabetes onset. The majority of children were diagnosed with diabetes in autumn and winter.