IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review.

This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children's health-from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular disorders. A comprehensive literature review was conducted using PubMed, with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method employing specific keywords related to child health, obesity, and insulin-like growth factors. This study reveals associations between insulin-like growth factor 1 and birth weight, early growth, and adiposity. Moreover, insulin-like growth factors play a pivotal role in regulating bone development and height during childhood, with potential implications for puberty onset. This research uncovers insulin-like growth factor 1 and insulin-like growth factor 2 as potential biomarkers and therapeutic targets for metabolic dysfunction-associated liver disease and hepatocellular carcinoma, and it also highlights the association between insulin-like growth factors (IGFs) and cancer. Additionally, this research explores the impact of insulin-like growth factors on cardiovascular health, noting their role in cardiomyocyte hypertrophy. Insulin-like growth factors play vital roles in human physiology, influencing growth and development from fetal stages to adulthood. The impact of maternal obesity on children's IGF levels is complex, influencing growth and carrying potential metabolic consequences. Imbalances in IGF levels are linked to a range of health conditions (e.g., insulin resistance, glucose intolerance, metabolic syndrome, and diabetes), prompting researchers to seek novel therapies and preventive strategies, offering challenges and opportunities in healthcare.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

Testicular torsion: its effect on autoimmunisation, pituitary-testis axis and correlation with primary gonadal dysfunction in boys.

BACKGROUND: Torsion of the testis is an urgent surgical condition that endangers the viability of the gonad and the fertility of the patient. Our aim was to assess potential autoimmune processes and hormonal abnormalities in boys operated on due to that illness. METHODS: The authors evaluated the levels of antibodies against sperm and Leydig cells, concentrations of follicle-stimulating, luteinizing and anti-Müllerian hormone, testosterone, oestradiol and vascular endothelial growth factor in the serum in 28 boys operated on due to torsion of the testis. Patients' sexual maturity was assessed according the Tanner scale (group G1, G4 and G5). RESULTS: No antibodies against sperm or Leydig cells were found in the serum. Statistically significant differences in follicle-stimulating and anti-Müllerian hormone concentrations were observed in the G1, and they were higher in the study than in the control group. There were no statistically significant differences in luteinizing hormone, testosterone, oestradiol and vascular endothelial growth factor concentrations in the study group or control group. Testosterone concentration was unrelated to total testicular volume. CONCLUSIONS: Results did not confirm the autoimmune process in boys with torsion of the testis. The pituitary-testis axis seems to have sufficient compensation capabilities. However, study results suggest that primary gonadal dysfunction may predispose to torsion. IMPACT: Significant differences exist between the literature data and own results on the formation of antibodies and hormonal changes due to testicular torsion in boys. It is a novel, prospective study on antibodies against sperms and Leydig cells in the serum and on hormonal processes occurring as a result of the testicular torsion from the prenatal period to the adolescence with division into pubertal groups. The study has revealed sufficient compensation capabilities of the pituitary-testis axis and no autoimmune process in boys with torsion of the testis.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.

Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review.

Achondroplasia (ACH) is a disease caused by a missense mutation in the FGFR3 (fibroblast growth factor receptor 3) gene, which is the most common cause of short stature in humans. The treatment of ACH is necessary and urgent because untreated achondroplasia has many complications, both orthopedic and neurological, which ultimately lead to disability. This review presents the current and potential pharmacological treatments for achondroplasia, highlighting the advantages and disadvantages of all the drugs that have been demonstrated in human and animal studies in different stages of clinical trials. The article includes the potential impacts of drugs on achondroplasia symptoms other than short stature, including their effects on spinal canal stenosis, the narrowing of the foramen magnum and the proportionality of body structure. Addressing these effects could significantly improve the quality of life of patients, possibly reducing the frequency and necessity of hospitalization and painful surgical procedures, which are currently the only therapeutic options used. The criteria for a good drug for achondroplasia are best met by recombinant human growth hormone at present and will potentially be met by vosoritide in the future, while the rest of the drugs are in the early stages of clinical trials.

Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1.

The autoimmune reaction against the beta cells of the pancreatic islets in type 1 diabetes mellitus (T1DM) patients is active in prediabetes and during the development of the clinical manifestation of T1DM, but it decreases within a few years of the clinical manifestation of this disease. A key role in the pathogenesis of T1DM is played by regulatory T cell (Treg) deficiency or dysfunction. Immune interventions, such as potential therapeutic applications or the induction of the Treg-cell population in T1DM, will be important in the development of new types of treatment. The aim of this study was to evaluate innovative immune interventions as treatments for T1DM. After an evaluation of full-length papers from the PubMed database from 2010 to 2021, 20 trials were included for the final analysis. The analysis led to the following conclusions: Treg cells play an important role in the limitation of the development of T1DM, the activation or application of Tregs may be more effective in the early stages of T1DM development, and the therapeutic use of Treg cells in T1DM is promising but requires long-term observation in a large group of patients.

Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland. METHODS: In this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland. RESULTS: Overall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17-year-olds. In the urban population (age 0-17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas. CONCLUSIONS: The incidence of T1D in children living in eastern and central Poland increased 1.5-fold over the 5-year observation period with the highest rise in 10 to 14-year-olds and significantly higher rates in urban children compared with their peers living in rural areas.

[Recurrent urolithiasis as a symptom of primary hyperparathyroidism in a 16-year-old boy]. / Nawracajaca kamica ukladu moczowego jako objaw pierwotnej nadczynnosci przytarczyc u 16-letniego chlopca.

Primary hyperparathyroidism is one of the most common endocrine diseases, however, it is rare in children. In most cases, it is caused by adenoma of these organs. Its most common complications include urolithiasis, nephrocalcinosis and osteoporosis. CASE REPORT: A 16-year-old patient was admitted to our Clinic because of his first-ever renal colic. The ultrasound examination revealed rightsided hydronephrosis caused by the presence of 9 mm stone in the upper part of the right ureter. In addition, the presence of 8 mm stone in the middle calyx of the left kidney was found. Due to the clinical picture, the patient was transferred to the urological department, where the effective ureterorenoscopic lithotripsy (URSL) was performed. Subsequent metabolic diagnostics showed hypercalcemia, hypophosphatemia, elevated levels of parathyroid hormone and hypercalciuria. In addition, the medical history revealed complicated, prolonged healing of a traumatic fracture of both bones of the left forearm in the last 12 months, requiring orthopedic treatment. Due to suspicion of primary hyperparathyroidism, parathyroid scintigraphy with MIBI scan by SPECT/ CT was performed. It revealed a focal lesion that could correspond to adenoma. The patient was referred to endocrinological care, but after 2 months he was readmitted to our Clinic, this time due to left renal colic. A left-sided ureteral stone was identified, which required another urological procedure. CONCLUSIONS: In differential diagnosis of urolithiasis in children, primary hyperparathyroidism should also be considered.

High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study.

AIM: Despite its characteristic symptoms, type 1 diabetes (T1D) is still diagnosed late causing the development of diabetic ketoacidosis (DKA). The aim of this study was to estimate the incidence of DKA and factors associated with the development of acidosis at T1D recognition in Polish children aged 0-17. METHODS: The study population consisted of 2100 children with newly diagnosed T1D in the years 2010-2014 in 7 hospitals in eastern and central Poland. The population living in these areas accounts for 35% of the Polish population. DKA was defined as a capillary pH < 7.3, blood glucose > 11 mmol/L. The analyzed data included age, sex, diabetes recognition, pH, glycated hemoglobin (HbA1c), fasting C-peptide, and body mass index standard deviation score (BMI-SDS). RESULTS: We observed DKA in 28.6% of children. There were 2 peaks in DKA occurrence: in children <5 years of age (33.9%) and aged 10-12 (34%). The highest incidence of DKA was noted in children aged 0-2 (48.4%). In the group with DKA, moderate and severe DKA occurred in 46.7% of children. Girls and children <2 years of age were more prone to severe DKA. The multiple logistic regression analysis showed the following factors associated with DKA: age (P = .002), fasting C-peptide (P = .0001), HbA1c (P = .0001), no family history of T1D (P = .0001), and BMI-SDS (P = .0001). CONCLUSIONS: The incidence of DKA is high and remained unchanged over the last 5 years. Increasing the awareness of symptoms of DKA is recommended among children <5 years of age (especially <2 years of age) and aged 10-12. Children <2 years of age and girls were at the highest risk of severe DKA.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.

Case Report: Adrenocortical carcinoma in children-symptoms, diagnosis, and treatment.

Adrenocortical carcinomas are extremely rare in the paediatric population. Most of them are hormone-secretive lesions; therefore, they should be taken into consideration in a child with signs of precocious puberty and/or Cushing's syndrome symptoms. Nonetheless, differentiation from benign adrenal tumours is necessary. We report a rare case of adrenocortical carcinoma in a girl and a literature review using the PubMed database. A four-year-old girl presented with rapidly progressing precocious puberty and signs of Cushing's syndrome. Imaging of the abdomen revealed a large heterogeneous solid mass. Histopathologic evaluation confirmed adrenocortical carcinoma with high mitotic activity, atypical mitoses, pleomorphism, necrosis, and vascular invasion. After tumourectomy, a decrease of previously elevated hormonal blood parameters was observed. Genetic tests confirmed Li Fraumeni syndrome. Adrenocortical carcinoma should be suspected in children with premature pubarche and signs of Cushing's syndrome. Diagnosis must be based on clinical presentation, hormonal tests, imaging, and histopathological evaluation. Complete surgical resection of the tumour is the gold standard. Oncological treatment in children is not yet well-studied and should be individually considered, especially in advanced, inoperable carcinomas with metastases. Genetic investigations are useful for determining the prognosis in patients and their siblings.

Premature pubarche during minipuberty - literature review and two case reports.

INTRODUCTION: Isolated premature pubarche (PP) in infancy may be the reason for many diagnostic difficulties. This is due to the low incidence and, therefore, the limited number of studies on this subject and the lack of strict laboratory standards because of the physiological variability of gonadotropic hormone and androgen concentrations during minipuberty. MATERIAL AND METHODS: We aimed to present current knowledge about PP in infancy based on the literature review and 2 cases of male infants with scrotal hair during minipuberty. RESULTS: Isolated hair in the pubic region in a boy during the period of minipuberty requires differential diagnosis. After excluding serious aetiology, it seems to be a mild, self-limiting variant of precocious puberty. The phenomenon is probably a result of increased sensitivity of the hair follicles to transiently increased androgen concentration. CONCLUSIONS: Isolated pubic hair in infancy as a mild, self-limiting variant of precocious puberty in infants should be a diagnosis of exclusion. The condition resolves spontaneously, but it absolutely requires further follow-up to exclude serious aetiology in the case of puberty progression.

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

INTRODUCTION: One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases. AIM: The aim of the study was to evaluate the population of NK cells and pancreatic ß cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases. MATERIAL AND METHODS: The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software. RESULTS: The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings. CONCLUSIONS: The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

Congenital Hypothyroidism in Preterm Newborns - The Challenges of Diagnostics and Treatment: A Review.

Preterm newborns are forced to adapt to harsh extrauterine conditions and endure numerous adversities despite their incomplete growth and maturity. The inadequate thyroid hormones secretion as well as the impaired regulation of hypothalamus-pituitary-thyroid axis may lead to hypothyroxinemia. Two first weeks after birth are pivotal for brain neurons development, synaptogenesis and gliogenesis. The decreased level of thyroxine regardless of cause may lead to delayed mental development. Congenital hypothyroidism (CH) is a disorder highly prevalent in premature neonates and it originates from maternal factors, perinatal and labor complications, genetic abnormalities, thyroid malformations as well as side effects of medications and therapeutic actions. Because of that, the prevention is not fully attainable. CH manifests clinically in a few distinctive forms: primary, permanent or transient, and secondary. Their etiologies and implications bear little resemblance. Therefore, the exact diagnosis and differentiation between the subtypes of CH are crucial in order to plan an effective treatment. Hypothyroxinemia of prematurity indicates dynamic changes in thyroid hormone levels dependent on neonatal postmenstrual age, which directly affects patient's maintenance and wellbeing. The basis of a successful treatment relies on an early and accurate diagnosis. Neonatal screening is a recommended method of detecting CH in preterm newborns. The preferred approach involves testing serum TSH and fT4 concentrations and assessing their levels according to the cut-off values. The possible benefits also include the evaluation of CH subtype. Nevertheless, the reference range of thyroid hormones varies all around the world and impedes the introduction of universal testing recommendations. Unification of the methodology in neonatal screening would be advantageous for prevention and management of CH. Current guidelines recommend levothyroxine treatment of CH in preterm infants only when the diagnose is confirmed. Moreover, they underline the importance of the re-evaluation among preterm born infants due to the frequency of transient forms of hypothyroidism. However, results from multiple clinical trials are mixed and depend on the newborn's gestational age at birth. Some benefits of treatment are seen especially in the preterm infants born <29 weeks' gestation. The discrepancies among trials and guidelines create an urgent need to conduct more large sample size studies that could provide further analyses and consensus. This review summarizes the current state of knowledge on congenital hypothyroidism in preterm infants. We discuss screening and treatment options and demonstrate present challenges and controversies.

Congenital Hyperinsulinaemic Hypoglycaemia-A Review and Case Presentation.

Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of persistent hypoglycaemia in infants and children with incidence estimated at 1 per 50,000 live births. Congenital hyperinsulinism (CHI) is symptomatic mostly in early infancy and the neonatal period. Symptoms range from ones that are unspecific, such as poor feeding, lethargy, irritability, apnoea and hypothermia, to more serious symptoms, such as seizures and coma. During clinical examination, newborns present cardiomyopathy and hepatomegaly. The diagnosis of CHI is based on plasma glucose levels <54 mg/dL with detectable serum insulin and C-peptide, accompanied by suppressed or low serum ketone bodies and free fatty acids. The gold standard in determining the form of HH is fluorine-18-dihydroxyphenyloalanine PET ((18)F-DOPA PET). The first-line treatment of CHI is diazoxide, although patients with homozygous or compound heterozygous recessive mutations responsible for diffuse forms of CHI remain resistant to this therapy. The second-line drug is the somatostatin analogue octreotide. Other therapeutic options include lanreotide, glucagon, acarbose, sirolimus and everolimus. Surgery is required in cases unresponsive to pharmacological treatment. Focal lesionectomy or near-total pancreatectomy is performed in focal and diffuse forms of CHI, respectively. To prove how difficult the diagnosis and management of CHI is, we present a case of a patient admitted to our hospital.

IPEX Syndrome: Genetics and Treatment Options.

(1) Background: IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome characterizes a complex autoimmune reaction beginning in the perinatal period, caused by a dysfunction of the transcription factor forkhead box P3 (FOXP3). (2) Objectives: Studies have shown the clinical, immunological, and molecular heterogeneity of patients with IPEX syndrome. The symptoms, treatment, and survival were closely connected to the genotype of the IPEX syndrome. Recognition of the kind of mutation is important for the diagnostics of IPEX syndrome in newborns and young infants, as well as in prenatal screening. The method of choice for treatment is hematopoietic stem cell transplantation and immunosuppressive therapy. In children, supportive therapy for refractory diarrhea is very important, as well as replacement therapy of diabetes mellitus type 1 (DMT1) and other endocrinopathies. In the future, genetic engineering methods may be of use in the successful treatment of IPEX syndrome. (3) Conclusions: The genetic defects determine a diagnostic approach and prognosis, making the knowledge of the genetics of IPEX syndrome fundamental to introducing novel treatment methods.

Thyroid Cancer Risk Factors in Children with Thyroid Nodules: A One-Center Study.

Thyroid nodules are common in the adult population (13%), but in childhood, they are relatively rarely diagnosed (0.2-5%). The risk factors and diagnostic and therapeutic algorithms are well-known and effectively used in adults, but no clear procedures supported by scientific research are available in the pediatric population. Our aim in this study was to identify predictive factors for thyroid cancer in a pediatric population. We retrospectively analyzed 112 children (80 girls and 32 boys, aged 0.6-18 years, with an average group age of 13.4 ± 4.5 years) with thyroid nodules who presented or were referred between 2010 and 2021. A total of 37 children qualified for partial or total thyroidectomy. After histopathological nodule examination, the most common cases were benign lesions in 23 patients (57.5%) and malignant lesions in 14 children (32.5%). Solitary benign thyroid nodules were found in 16 children (40%). Malignancy risk was higher in children with increased nodule diameter (greater than 7 mm; p = 0.018) or hypoechogenic lesions in ultrasound (p = 0.010), with no correlation between increased blood flow in the vessels and tumor diagnosis. The relative risk of developing thyroid cancer for class III was found to be higher in comparison to adults and 11.1 times higher than for classes I and II combined.

Craniofacial Morphology in Children with Growth Hormone Deficiency and Turner Syndrome.

The review aims to collect and demonstrate recent knowledge about craniofacial morphology in growth hormone (GH)-deficient children and children with Turner syndrome. The review describes also the effects of growth hormone treatment on craniofacial morphology of children with growth hormone deficiency and Turner syndrome. Regardless of the disorder it accompanies, short stature is associated with similar craniofacial features characteristic of all short-statured children. Characteristic craniofacial features involve lesser dimensions of the cranial base and mandibular length, proportionately smaller posterior than anterior facial height, retrognathic face, and posterior rotation of the mandible. We also analyze orthodontic treatment in children affected by disorders associated with GH deficiency or provided with growth hormone treatment in the aspect of craniofacial growth. Recent publications show also the connection between growth hormone receptor polymorphism and craniofacial growth. Specialists and orthodontists treating short-statured children must be aware of the results of studies on craniofacial morphology and educate themselves on the topic of craniofacial growth in children with short stature. Moreover, knowledge of the influence of GH therapy on growth of craniofacial structures is necessary to decide the proper timing and planning of orthodontic treatment.

Interaction of lymphocytes and thyrocytes in Graves' disease and nonautoimmune thyroid diseases in immunohistochemical and ultrastructural investigations.

BACKGROUND: Graves' disease is the archetype for organ-specific autoimmune disorders. It is very important for our understanding of the mechanisms responsible for progression of autoimmunity. The aim of this study was to present interactions of lymphocytes and thyrocytes in the thyroid tissue in Graves' disease and nonautoimmune thyroid diseases. METHODS: The study involved 30 children with Graves' disease, 30 children with nodular goiter, 30 with simple goiter and 30 healthy children. After thyroidectomy, T cells were detected in the thyroid specimens by CD3, CD4, CD8 antibodies, B cells by CD79alpha antibodies and the antigen-presenting dendritic cells with CD1a antibodies (DakoCytomation) and were examined in the EM 900 Zeiss Germany Electron Microscope. RESULTS: The most enhanced immune reaction was observed in the thyroid from children with Graves' disease. The cells of the immune system infiltrated the thyroid follicles and interfollicular compartments; they also formed lymph follicles. CONCLUSION: The immune reaction in Graves' disease and migration of lymphocytes T and B between thyrocytes results in the thickening of the basal membrane of the thyroid follicle. No cytotoxic effect of T cytotoxic/suppressor CD8+ cells on thyrocytes was observed in Graves' disease, while a mild cytotoxic effect was observed in non-autoimmune thyroid disease.

Cortisol, leptin and free leptin index (FLI) in newborns in the first days of life and their importance for body weight programming.

BACKGROUND: Birth weight and leptin seem to be the factors responsible for early programming of body weight in later life. A marker for leptin action is free leptin index (FLI), which depends on soluble leptin receptor (Ob-Re) (FLI = leptin/Ob-Re). In the present article, we suggest that FLI is modulated partly by cortisol variations observed in newborns in the first days of life and is connected with their postnatal weight loss. METHODS: The study group consisted of 44 full-term newborns. Leptin, cortisol and Ob-Re concentrations were determined in the umbilical cord blood (UCB) and in the newborns' blood (NB) on the fourth day of life, free leptin index (FLI = leptin/Ob-Re) was calculated. Correlations between the assessed parameters and the somatic features of the newborns were examined. RESULTS: Birth weight, length and chest circumference of newborns were positively correlated with leptin concentration in the UCB but not with FLI in the UCB. Cortisol and leptin concentrations, as well as FLI values declined concomitantly with body weight, and were lower on the fourth day of life than on the first one; however, Ob-Re concentration increased (p < 0.0001). There was a positive correlation between the newborns' birth weight loss percentage evaluated on the fourth day of life and FLI in newborns (R = 0.39; p < 0.01). Positive correlations between cortisol and Ob-Re in UCB (R = 0.35; p < 0.02) and in NB (R = 0.36; p < 0.01), as well as a negative correlation between cortisol and FLI (R = -0.32; p < 0.03) in NB were noted. CONCLUSIONS: Our data suggest a possible relationship between cortisol and a soluble leptin receptor (Ob-Re), which changes free leptin index (FLI) and is connected with birth weight loss in newborns. Whether these observations are important for programming of future body weight of children requires further research.