Changes in body proportions and body fat content in GH-deficient and non-GH-deficient children during the first year of growth hormone treatment.

Introduction: The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether and how the recombinant human growth hormone (rhGH) treatment affects the trunk-limb proportions. Aim of the study: We aim to evaluate the changes in body proportions and body fat content in short children with growth hormone deficiency (GHD), children born small for gestational age (SGA), and girls with Turner syndrome (TS) during the first year of rhGH therapy. Material and methods: The data of 70 children with GHD, 40 children born SGA, and 36 girls with TS from 1998 to 2019 were analyzed. The following parameters were measured: height, body weight, sitting height, and two skinfolds on the arm above the triceps brachii and below the scapula at the beginning of rhGH therapy and after the first year of treatment. Sitting height and lower limb length were presented as percentages (%) of body height. Fat mass percentage (%FAT) was calculated using the Slaughter formula. Results: At the beginning of rhGH, TS girls had the greatest height deficit (-2.7 SDS), the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and children born SGA. Moreover, TS girls had higher body weight SDS, BMI SDS compared to SGA children (p < 0.001), and higher %FAT compared to both GHD and SGA children (p < 0.001 for both). After the first year of rhGH therapy, a significant increase in lower limb share (%) and a decrease in %FAT were observed in all the study groups. TS girls still had significantly higher sitting height (%), shorter lower limbs (%), and higher %FAT, body weight SDS, and BMI SDS compared to children with GHD and children born SGA (p < 0.05 for all variables). Conclusions: Our results show that rhGH treatment could increase lower limb length in relation to height and reduce fat mass in treated children. Girls with TS had the largest baseline body disproportions and the highest body fat content. Despite a satisfactory reduction in height deficit, after the first year of rhGH therapy, these girls had still higher body weight SDS, BMI SDS, %FAT, the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and born SGA.

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.

Obesity and chronic inflammation crosslinking.

The adipose tissue has been recognized as an active organ involved in numerous metabolic, hormonal and immunological processes. Obesity and associated chronic inflammation leads to many metabolic and autoimmune disorders. The number of cells, their phenotype and distribution in adipose tissue depends on the degree of obesity. Polarization of macrophages towards M1, neutrophils influx to adipose tissue, activation of Th1 and Th17 cells and increased level of proinflammatory cytokines are characteristic for obesity-induced inflammation. Several mechanisms, such as adipocytes' hypoxia, oxidative stress, endoplasmic reticulum stress, impairment of PPAR receptors, inflammasomes' activation and activation of TLR are involved into development of chronic obesity-induced inflammation. A better understanding of this processes can provide new treatments for obesity and related disorders.

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.

Graves' disease in children in the two decades following implementation of an iodine prophylaxis programme.

Grave's disease (GD) is a form of thyroid autoimmune disease characterised by hyperthyroidism. It is a rare clinical problem in paediatrics. Development of disease is the result of genetic susceptibility and some environmental factors. One of the best-documented environmental factors involved in thyroid autoimmunity is iodine excess. The aim of our study was to analyse the clinical course and response to pharmacological treatment in children diagnosed with Graves' disease in first two decades after mandatory salt iodination. Records of 94 children diagnosed with GD in the years 1998-2017 were analysed. Medical data of patients was compared between two decades following implementation of iodine prophylaxis: 1998-2007 (first-decade group - FDG) and 2008-2017 (second-decade group - SDG); 34 and 60 patients, respectively. Medical data of FDG was obtained from archival records and previous analysis performed in 2006. Data of 60 patients from SDG were obtained from currently available medical records. Results were statistically analysed using Microsoft Excel and Statistica 11 software. Results: In our study, after mandatory salt iodination, the tendency of an increase in newly diagnosed GD in children without family susceptibility was observed. The antibody profile indicates the significant contribution of the autoimmune process involving all thyroid antigens; therefore, the term "autoimmune hyperthyroidism" seems to be more appropriate than classical GD in this group of patients. The first-choice treatment with methimazole rarely causes adverse events during the therapy, and they have benign character.