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.

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.

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.

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.

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.

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.

Growth hormone deficiency as a complication of haemophilia - a case report and literature data.

Severe haemophilia carries an increased risk of life-threatening intracranial haemorrhages. Studies in adult survivors show a relatively high percentage of anterior pituitary hypofunction reported as the most frequent complication. We report the case of isolated growth hormone deficiency in a boy with severe haemophilia A. He experienced several intracranial haemorrhages in early childhood. At the age of seven years, growth hormone deficiency was diagnosed. The MRI scan of the pituitary gland was normal, but many focal changes in brain tissue were found. The function of pituitary-dependent hormonal axes beyond GH/IGF1 axis was sufficient. Therapy with rhGH was introduced and continued for over nine years. Growth velocity increased and the height normalised appropriately to parental height. We did not observe any complications besides sporadic subcutaneous bleedings. Patients with haemophilia should be considered as a high-risk group for hypopituitarism. Subcutaneous rhGH injections can be safe even in severe haemophilia.

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.

Gender-Dependent Growth and Insulin-Like Growth Factor-1 Responses to Growth Hormone Therapy in Prepubertal Growth Hormone-Deficient Children.

Gender seems to be an important factor influencing the response to recombinant human growth hormone (rhGH) therapy in GH-deficient adolescents and adults. The results of studies evaluating gender-specific response to rhGH therapy in prepubertal GH-deficient children are divergent. The aim of this study was to determine the effect of gender on the growth and insulin-like growth factor-1 (IGF-1) responses in 75 prepubertal GH-deficient children during the first 2 years of rhGH therapy. There were no baseline gender differences in age, bone age, anthropometrical parameters, and IGF-1 SDS for bone age. After the initiation of rhGH therapy, there were no gender-specific differences concerning the reduction of height deficit. Serum IGF-1 levels were higher in the prepubertal GH-deficient girls than in the age-matched boys, but the difference was not significant when expressed as IGF-1 SDS for bone age. The increase in IGF-1 SDS for bone age was significantly greater in girls versus boys after the first 6 months of therapy, comparable between girls and boys after the first year of therapy, and tended to be higher in boys after the second year of therapy. In conclusion, prepubertal GH-deficient girls and boys do not differ significantly in growth response in the first 2 years of rhGH therapy.

Thyroid function in children with growth hormone deficiency during long-term growth hormone replacement therapy.

AIM OF THE STUDY: The aim of this study was to investigate the effects of growth hormone (GH) therapy on thyroid function in a group of euthyroid children with isolated idiopathic growth hormone deficiency (GHD). MATERIAL AND METHODS: The study was retrospective and included 117 children treated with GH for 1-4 years. Anthropometric measurements and serum concentrations of insulin-like growth factor-1 (IGF-1), thyroid-stimulating hormone (TSH), and free thyroxine (fT4) were analysed at baseline and during GH therapy. RESULTS: TSH levels did not change significantly after the initiation of GH treatment, while fT4 levels decreased after the second year of GH treatment (p < 0.01) and remained lower than baseline until the end of observation (p < 0.01, after both the third and fourth year of therapy) in the whole group. Analysis according to baseline pubertal status revealed significant changes in TSH and fT4 levels during GH treatment, but only in the prepubertal children. Multiple regression analysis confirmed that mean GH doses administered in the first two years of GH therapy were independently (R = 0.218, p < 0.05) associated with changes in fT4 levels in this period (∆fT42 years - baseline), even when taking into account changes in height SDS and bone age. CONCLUSIONS: FT4 levels decreased during GH replacement therapy, while TSH levels appeared to be unaffected by GH therapy. Prepubertal children seem to be more predisposed to thyroid function alterations during such therapy in comparison to pubertal children. Changes in fT4 levels during GH replacement therapy are related to GH doses.

Usefulness of the Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C) in prediction of metabolic syndrome in Polish obese children and adolescents.

The triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) is a useful surrogate marker of insulin resistance and cardiovascular risk factors. We aimed to assess the relationship between the TG/HDL-C ratio and insulin resistance (IR) and its usefulness in prediction of the metabolic syndrome (MS). This retrospective study involved 122 obese children with the mean age of 11.6±3 years and their 58 healthy lean peers. Anthropometric measurements, blood pressure, the plasma lipid profile and oral glucose tolerance test (OGTT) were analyzed. Based on the obtained results, the TG/HDL-C ratio and surrogate insulin resistance indices (HOMA-IR, FGIR, QUICKI, OGIS, Matsuda index) were calculated. The TG/HDL-C ratio positively correlated with weight, waist circumference, waist to hip ratio (WHR), lipid profile, HOMA-IR, fasting insulin and insulin measurements during OGTT, and negatively correlated with FGIR, QUICKI, OGIS, and the Matsuda index. Obese children with the TG/HDL-C ratio≥3 (47.5%) had higher values of WHR and HOMA-IR, and lower ones of FGIR, QUICKI, OGIS, and the Matsuda index when compared to their obese peers with the TG/HDL-C<3. The area under the curve (AUC) calculated for each insulin resistance index in prediction of the metabolic syndrome was the largest for the TG/HDL-C ratio (0.8936, 95% Cl:0.809-0.977, p=0.000). For 1 unit increase in the TG/HDL-C ratio, the odds for having MS increased by 2.09 times. The TG/HDL-C ratio is a good surrogate marker of insulin resistance in obese children. When comparing the usefulness of some IR markers in prediction of the metabolic syndrome, the TG/HDL-C ratio seems to be the best one and should be used in clinical practice to identify children at risk of metabolic syndrome development.

Osteoprotegerin, Receptor Activator of Nuclear Factor Kappa B Ligand, and Growth Hormone/Insulin-Like Growth Factor-1 Axis in Children with Growth Hormone Deficiency.

The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is involved in the regulation of the receptor activator of nuclear factor kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system, but the exact mechanism of the associations is not fully explained. In this study we investigated the serum OPG and total sRANKL concentrations in short children who had differences in GH secretory status. We also investigated the associations between the GH/IGF-1 and OPG/RANKL systems in GH-deficient children during GH treatment. There were no significant differences in any anthropometric or biochemical parameters evaluated between the GH-deficient and GH-sufficient children. The OPG content and total alkaline phosphatase (ALP) activity increased significantly after the initiation of GH treatment, while total sRANKL remained unchanged. The variables baseline BMI SDS for height-age (ß = 0.42; p < 0.05), baseline ALP activity (ß = 0.36; p < 0.05), weight SDS for height-age at 6 months of GH treatment (ß = 1.86; p < 0.01), and total ALP activity at 6 months of GH treatment (ß = 0.48, p < 0.01) were identified as independent predictors of ΔOPG6-month-baseline. We conclude that OPG and total sRANKL concentrations are independent from GH secretory status in short children. OPG elevation during GH treatment is independently associated with total ALP activity and nutritional status in GH-deficient children.

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.

The pre-treatment characteristics and evaluation of the effects of recombinant human growth hormone therapy in children with growth hormone deficiency and celiac disease or inflammatory bowel disease.

THE AIM OF THE STUDY: was to investigate the coincidence of growth hormone deficiency (GHD) and celiac disease (CD) or inflammatory bowel disease (IBD) in patients referred for short stature, and to evaluate the baseline anthropometric parameters and the effectiveness of recombinant human growth hormone (rhGH) therapy in the first year in those patients (GHD+CD/IBD subgroup) in comparison to patients with GHD without CD or IBD (GHD-CD/IBD subgroup). MATERIAL AND METHODS: The study was retrospective and included 2196 short patients (height SDS [Standard Deviation Score] ≤ -1.2). 1454 patients had height SDS ≤ -2. Twenty-nine patients suffered from CD or IBD. GHD was confirmed in 419 patients with height SDS ≤ -2. The coexistence of GHD and CD or IBD was found in seven patients (GHD+CD/IBD subgroup). RESULTS: At baseline the GHD-CD/IBD subgroup did not differ significantly in chronological age, height SDS, height velocity (HV) before rhGH therapy, body weight SDS, and body mass index SDS from the GHD+CD/IBD subgroup. The improvement in height SDS within the first year of rhGH therapy was higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup and the difference was statistically significant (p<0.05). HV in the first year of rhGH therapy was also significantly higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup (p < 0.05). CONCLUSIONS: In patients with chronic inflammatory disorders of the gastrointestinal tract, especially celiac disease, coexisting with GHD, rhGH therapy could be effective and should be administered together with therapy of primary gastrointestinal disease.

The relationship between alkaline phosphatase and bone alkaline phosphatase activity and the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency.

The relationships between bone turnover, the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and vitamin D are complex, but still not fully explained. The GH/IGF-1 axis and vitamin D can mutually modulate each other's metabolism and influence the activation of cell proliferation, maturation, and mineralization as well as bone resorption. The aim of this study was to evaluate the reciprocal associations between bone formation markers [alkaline phosphatase (ALP), bone alkaline phosphatase (BALP)], the GH/IGF-1 axis and 25-hydroxyvitamin D [25(OH)D] in children with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) therapy. ALP, BALP, 25(OH)D and IGF-1 levels were evaluated in 53 patients included in this prospective three-year study. ALP, BALP and IGF-1 increased during rhGH therapy. Baseline ALP activity correlated positively with baseline height velocity (HV). ALP and BALP activity at 12 months correlated positively with HV in the first year of therapy. We found positive correlations between ALP and IGF-1 at baseline and during the first year of therapy, between BALP activity at 12 months and rhGH dose in the first year of therapy, and between doses of cholecalciferol in the first year of rhGH therapy and early changes in BALP activity during rhGH therapy. Our results indicate that vitamin D supplementation enhances the effect of rhGH on bone formation process, which could improve the effects of rhGH therapy. ALP and BALP activity are useful in the early prediction of the effects of rhGH therapy, but their utility as long-term predictors seemed insufficient.

Serum TSH level in obese children and its correlations with atherogenic lipid indicators and carotid intima media thickness.

Objective: Moderately elevated level of thyroid-stimulating hormone accompanied by normal serum concentrations of free thyroxine, suggesting subclinical hypothyroidism, is the most common hormonal abnormality in obese children. Controversy remains, whether a thyroid dysfunction related to obesity has an influence on the cardiovascular risk factors. The aim of the study was to assess correlation between thyroid-stimulating hormone and free thyroxine and chosen atherogenic lipid indicators, and carotid intima media thickness in obese children and adolescents. Methods: A study group consisted of 110 obese children (11.5 ± 2.9 years) and 38 healthy children (13.4 ± 2.6 years). Obesity was defined using International Obesity Task Force criteria. In each patient anthropometric measurements, thyroid-stimulating hormone, free thyroxine, a lipid profile were evaluated. Carotid intima-media thickness was measured in 74 obese children and 28 lean children. The resulting data were used to calculate indicators of atherogenesis: total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio and LDL cholesterol to HDL cholesterol ratio. Results: Obese children had higher mean serum thyroid-stimulating hormone levels compared to their lean peers and an adverse atherogenic lipid profile. Serum free thyroxine concentrations were comparable between the groups. Serum thyroid-stimulating hormone values correlated with total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio, LDL cholesterol to HDL cholesterol ratio, and intima-media thickness. In a multivariate regression analysis, thyroid-stimulating hormone weakly correlated only with intima-media thickness after adjustment for age, gender and Body Mass Index (ß = 0.249, p = 0.04). This relationship weakened after considering a lipid profile (ß = 0.242, p = 0.058). No relationship was found for free thyroxine. Conclusion: Serum level of thyroid-stimulating hormone in obese children did not seem to impact atherogenic lipid indicators and carotid intima-media thickness. Therefore, an adverse lipid profile should still be considered the main risk factor for development of cardiovascular diseases in obese children.Objective: Moderately elevated level of thyroid-stimulating hormone accompanied by normal serum concentrations of free thyroxine, suggesting subclinical hypothyroidism, is the most common hormonal abnormality in obese children. Controversy remains, whether a thyroid dysfunction related to obesity has an influence on the cardiovascular risk factors. The aim of the study was to assess correlation between thyroid-stimulating hormone and free thyroxine and chosen atherogenic lipid indicators, and carotid intima media thickness in obese children and adolescents. Methods: A study group consisted of 110 obese children (11.5 ± 2.9 years) and 38 healthy children (13.4 ± 2.6 years). Obesity was defined using International Obesity Task Force criteria. In each patient anthropometric measurements, thyroid-stimulating hormone, free thyroxine, a lipid profile were evaluated. Carotid intima-media thickness was measured in 74 obese children and 28 lean children. The resulting data were used to calculate indicators of atherogenesis: total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio and LDL cholesterol to HDL cholesterol ratio. Results: Obese children had higher mean serum thyroid-stimulating hormone levels compared to their lean peers and an adverse atherogenic lipid profile. Serum free thyroxine concentrations were comparable between the groups. Serum thyroid-stimulating hormone values correlated with total cholesterol to HDL cholesterol ratio; triglycerides to HDL cholesterol ratio, LDL cholesterol to HDL cholesterol ratio, and intima-media thickness. In a multivariate regression analysis, thyroid-stimulating hormone weakly correlated only with intima-media thickness after adjustment for age, gender and Body Mass Index (ß = 0.249, p = 0.04). This relationship weakened after considering a lipid profile (ß = 0.242, p = 0.058). No relationship was found for free thyroxine. Conclusion: Serum level of thyroid-stimulating hormone in obese children did not seem to impact atherogenic lipid indicators and carotid intima-media thickness. Therefore, an adverse lipid profile should still be considered the main risk factor for development of cardiovascular diseases in obese children.

Association Between Vitamin D and Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen in Children During Growth Hormone Replacement Therapy.

Growth hormone and insulin-like growth factor-1 (IGF-1) play a crucial role in the regulation of bone turnover. Adequate vitamin D status supports proper bone remodeling, leading to normal longitudinal bone growth and normal peak bone mass. The aim of this study was to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] and carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) in children and adolescents with growth hormone deficiency at baseline and during recombinant human growth hormone (rhGH) replacement therapy. The study was prospective and included 30 children and adolescents aged 5 to 17 years. Concentrations of 25(OH)D, ICTP, and IGF-1 were measured at baseline and during the first year of rhGH therapy. Baseline serum 25(OH)D concentration correlated with ICTP concentrations during the first trimester of rhGH therapy (r = 0.38, p < 0.050); the correlation was stronger in the second trimester of therapy (r = 0.6, p = 0.002). We conclude that proper vitamin D status is important in reaching the adequate dynamics of bone remodeling during growth, which is essential to achieve a catch-up growth during rhGH therapy.