Ewelina Witkowska-Sędek

Relationship Between 25(OH)D and IGF-I in Children and Adolescents with Growth Hormone Deficiency

Recent studies have shown that vitamin D has an impact on the production and secretion of IGF-I in the liver. The aim of our study was to investigate the relationship between the concentrations of 25-hydroxy vitamin D [25(OH)D] and insulin-like growth factor I (IGF-I) in growth hormone deficient children and adolescents before recombinant human growth hormone (rhGH) treatment. The study was retrospective and included 84 children and adolescents aged 4-17. Prior to initiating rhGH therapy, concentrations of 25(OH)D and IGF-I were measured in all patients. IGF-I concentrations were normalized for bone age. The studied group was divided into two subgroups according to serum 25(OH)D levels. Significant positive correlations between 25(OH)D concentration and IGF-I SDS-normalized for bone age were observed in both studied subgroups. The results of our study suggest that vitamin D deficiency could influence IGF-I concentrations in children and adolescents with growth hormone deficiency, and vitamin D deficiency should be normalized before the measurement of IGF-I concentrations to obtain the reliable and unbiased IGF-I values.

Thyroid dysfunction in obese and overweight children

Obesity and thyroid function are closely related. Thyroid hormones are involved in the regulation of metabolism, thermogenesis, food intake, and fat oxidation. In obese children the most frequent hormonal abnormalities are slight hyperthyrotropinaemia and moderate increases in total T3 and/or fT3 concentrations. Those abnormalities are usually considered a cause of obesity, but according to recent studies, they should actually be considered an adaptation process aimed at increasing resting energy expenditure and total energy expenditure. Those abnormalities do not require any treatment and normalise after substantial weight loss. The mechanisms of those changes are dependent on leptin, thyroid hormone resistance, and mitochondrial dysfunction. The present paper describes the abovementioned mechanisms based on the latest research. We also present a review of some recent original studies evaluating thyroid function in overweight and obese children, including thyroid ultrasound. A thyroid ultrasound scan in obese children frequently shows increased thyroid volume, which correlates with moderately increased TSH levels and a hypoechoic pattern typical of autoimmune thyroiditis, but without antithyroid autoantibodies. Alterations of thyroid function in overweight and obese patients cause an increase in energy expenditure, which facilitates weight loss and prevents further weight gain. Therefore, normalisation of TSH and fT3 after weight loss could explain difficulties in maintaining reduced weight. (Endokrynol Pol 2017; 68 (1): 54-60).

Thyroid Function in Obese Children and Adolescents and Its Association with Anthropometric and Metabolic Parameters

Fat accumulation leads to dysfunction of hypothalamic-pituitary-thyroid axis and to changes in thyroid function. A higher serum level of thyroid stimulating hormone (TSH), with normal levels of thyroid hormones, suggesting subclinical hypothyroidism, is often found in obese individuals. The influence on lipid and glucose metabolism of thyroid dysfunction in obese patients remains unclear. This retrospective study encompassed 110 obese children and 38 healthy non-obese children aged 5-18. Anthropometric measurements, including bioelectrical impedance, were taken in all children. Fasting TSH, fT4, glucose, lipid profile, and a glucose tolerance test in case of the obese individuals, were evaluated. The obese children demonstrated a significantly higher mean concentration of TSH compared with their peers with proper body weight: 2.1 ± 1.0 μIU/ml vs. 1.5 ± 0.6 μIU/ml, p = 0.001. The fT4 was not different between the two groups. In the obese children, TSH correlated with body mass index (BMI) and waist circumference after controlling for age and gender. A multivariate regression analysis showed a relationship of TSH with total cholesterol, LDL cholesterol, triglycerides, and non-HDL after adjusting for BMI. None of these relationships were revealed for fT4. The level of TSH correlated with the degree of abdominal obesity. We conclude that the serum TSH concentration, even remaining within the norm, could adversely affect the lipid profile, irrespective of obesity.

Metabolic and Immunological Consequences of Vitamin D Deficiency in Obese Children

Numerous studies highlighted the link between vitamin D deficiency and cardiovascular, autoimmune, metabolic diseases, and obesity. However, a clear role of vitamin D in these disorders is still unknown. Vitamin D deficiency in children can be a potential risk factor for developing diseases at a later age. Early prevention and vitamin D supplementation should become a public health priority. This review highlights the clinical implications of vitamin D deficiency in adults and children with obesity.

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 others 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.

Thyroid Autoimmunity in Girls with Turner Syndrome

Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

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 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.

Adrenal abscess in a 3-week-old neonate - a case report.

The authors present a case of a 6-year-old boy operated on in the 4th week of life because of adrenal abscess. The diagnosis of an adrenal abscess in the neonatal period is challenging due to its rare occurrence and non-specific signs. Adrenal abscesses can develop via two mechanisms: as a result of a hematogenic infection and a spread of bacteria to “normal” adrenal glands or, which is much more common, a complication of an adrenal hematoma. Early and accurate diagnosis is crucial for appropriate therapeutic management. Imaging, including ultrasound, can be problematic. The final diagnosis is frequently established on the basis of a histological examination of a surgical specimen.