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.

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.

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.

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.

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.

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.

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.

[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.

Premature atherosclerosis after treatment for acute lymphoblastic leukemia in childhood.

INTRODUCTION: Late cardiovascular complications are the leading causes of morbidity and mortality in patients treated for common malignancies of childhood. Late cardiotoxicity include increased development of atherosclerosis and atherosclerosis - related diseases. An evaluation of the endothelium can be made based on the measurement of endothelium-derived blood vasoactive factors, such as cytokines and adhesion molecules. Their elevated serum levels may serve as sensitive indicators of early atherosclerotic lesions in high risk patients. Currently, assessment of common carotid intima-media thickness has emerged as one of the more powerful tools for evaluation of subclinical atherosclerosis. The purpose of this study was to compare these parameters between patients after antineoplatic treatment compared to persons not exposed to such factors. MATERIAL AND METHODS: Early progression of atherosclerotic disease was evaluated in 64 survivors treated for Acute Lymphoblastic Leukaemia (ALL) in childhood, and in a control group of 36 healthy volunteers. Blood serum concentrations of selected new biomarkers, indicative of endothelial damage and inflammatory activity, were measured, including intercellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (E-selectin), thrombomodulin (TM), interleukin 6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The common carotid intima-media thickness (IMT) was also assessed via ultrasound examination. RESULTS: Significantly higher blood concentrations of sICAM-1 adhesive molecule (229.3±62.2 ng/mL vs. 199.9 ± 63.3 ng/ mL, p=0.0072) and IL-6 (2.1 ± 2.7 pg/mL vs. 1.9 ± 3.6 pg/mL, p=0.0414) were found in ALL survivors compared with control subjects. Concentration of hs-CRP was also higher in the ALL group: 1.3 ± 2.2 ug/mL vs. 0.6 ± 0.9 ug/mL. This difference was close to statistical significance (p=0.0599). The mean IMT values for right and left carotid arteries were higher in ALL patients after antineoplastic therapy, compared with healthy subjects (IMT-R 0.056±0.008 mm vs. 0.052±0.003 mm; p=0.0021; IMT-L 0.057±0.009 mm vs. 0.052±0.003 mm; p=0.0051). CONCLUSIONS: Survivors of childhood ALL in the examined group demonstrated elevated concentrations of selected new biomarkers and increased IMT values, compared to controls, which may confirm the occurrence of endothelial injuries in blood vessels. This study indicates that subjects treated for childhood malignancy are at a higher risk of prematurely developing atherosclerosis.

A new CO2 laser technique for the treatment of pediatric hypertrophic burn scars: An observational study.

Treatment of hypertrophic scars arising as a result of thermal burns in children is still a big problem. The results of the treatment are not satisfactory for patients and parents, and new methods of treatment are still investigated.We present the use of one of the most modern carbon dioxide (CO2) lasers (Lumenis Encore laser equipped with a Synergistic Coagulation and Ablation for Advanced Resurfacing module) in the treatment of hypertrophic scars in children after burns.From March to April of 2013, a group of 47 patients aged 6 to 16 years underwent 57 laser surgery treatments. The average time from accident was 7.5 years. The results of treatment were investigated in 114 areas. The assessed areas were divided into 2 groups: 9-cm area 1, where the thickness of the scar measured by physician was the lowest and 9-cm area 2, where the thickness of the scar was the biggest. The results were considered on the Vancouver Scar Scale (VSS) independently by the surgeon and by parents 1, 4, and 8 months after the procedure. In addition, ultrasound evaluation of the scar thickness before and after laser procedure was made.VSS total score improved in all areas assessed by both the physician and parents. The biggest change in total VSS score in area 1 in the evaluation of the investigator was obtained at follow-up after the 1st month of treatment (average 7.23 points before and 5.18 points after the 1st month after surgery-a difference of 2.05 points). Scar ratings by parents and the physician did not differ statistically (P < 0.05). In the ultrasound assessment, the improvement was statistically significant, more frequently for both minimum and maximum thickness of the scars (B-mode measures) (P < 0.05).The use of a CO2 laser in the treatment of hypertrophic scars in children is an effective and safe method. The use of a CO2 laser improves the appearance and morphology of scarring assessed using the VSS by both the parents and the physician. The treatment also reduced the thickness of scars evaluated by ultrasound.

From arterial hypertension complications to von Hippel-Lindau syndrome diagnosis.

Von Hippel-Lindau syndrome is a rare, genetically based, autosomal dominant disorder. Its course is accompanied by the development of multiple neoplasms with the following tumours diagnosed most commonly in the central nervous system haemangioblastoma, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, and endolymphatic sac tumours. Additionally, renal and pancreatic cystadenomas and epididymal cystadenomas have been diagnosed in males and cystadenomas of the broad ligament of the uterus have been diagnosed in females.The following paper presents the diagnostic way in a boy with vision disorders as the first symptom. Hypertension retinopathy and extremely elevated blood pressure were observed during ophthalmologic consultation. Complications of arterial hypertension were confirmed by echocardiography, which diagnosed hypertension cardiomyopathy. Hypertension retinopathy was confirmed by optical coherence tomography. Examinations performed in the neurology, cardiology, and finally endocrinology indicated a bilateral phaeochromocytoma as the cause of arterial hypertension. Moreover, some genetic investigations showed a mutation in the VHL ex.1 p.Y112 C gene responsible for the hereditary form of phaeochromocytoma which confirmed von Hippel-Lindau syndrome. After surgical treatment of phaeochromocytoma the patient needed careful management according to the surveillance protocol for von Hippel-Lindau disease.

Von Hippel-Lindau Syndrome.

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by the development of multiple vascular tumours. The syndrome is caused by inactivation of the VHL protein (pVHL) and increased production of VEGF, PDGF, and TGF-α. The course of VHL syndrome is associated with the development of multiple vascular tumours. Most frequently, these include retinal and central nervous system haemangioblastomas, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, endolymphatic sac tumours, and additionally, renal and pancreatic cystadenomas and epididymal cystadenomas in men. VHL syndrome is a highly complex disease; hence, the diagnosis is often difficult. The diagnosis of any of the characteristic tumours, particularly in children, is an implicit indication for the necessity of diagnosis and genetic tests in the patient and family members and for intensive supervision of carriers of the mutated gene, thereby improving early diagnosis and successful treatment of the malignancies.

Testicular adrenal rest tumors in boys with congenital adrenal hyperplasia: 3D US and elastography--do we get more information for diagnosis and monitoring?

BACKGROUND: Testicular adrenal rest tumors (TART) are the nodular testicular lesions deriving from the adrenal remnant tissue reported in boys and men with congenital adrenal hyperplasia. Until now, the diagnostics of TART have been based on a combination of clinical features, imaging methods (primarily two dimensional ultrasound--2D US), response of the foci to glycocorticosteroid (GCS) therapy and exclusion of the neoplastic process. Application of 2D US supplies however a limited range of information about the volume, demarcation, structure and vascularization of the lesions. OBJECTIVE: To define whether the use of 3D US, power Doppler and elastography changes the algorithm of the diagnostics and monitoring or treatment of TART. MATERIAL AND METHODS: In this study, modern ultrasound techniques such as 3D US and elastography were introduced in two boys with TART. RESULTS: The 3D power Doppler option gives the opportunity for accurate assessment of the volume of testes and adrenal tissue foci and their vascularization. Sonographic elastography allows the assessment of stiffness of adrenal tissue areas compared to normal testis parenchyma. CONCLUSION: The use of these modern techniques enables more adequate and advanced diagnostics, and more precise monitoring of the effects of treatment in patients with TART.

The differences in T and B cell subsets in thyroid of children with Graves' disease and Hashimoto's thyroiditis.

BACKGROUND: The differences between Graves' disease (GD) and Hashimoto's thyroiditis (HT) suggest that changes in the subsets of T cells may have an influence on the course of these reactions. METHODS: This study included 90 children: 30 with GD, 30 with HT, and 30 healthy children as controls. After thyroidectomy, standard histological examinations and immunohistochemical reactions were performed in paraffin specimens with monoclonal antibodies against T cell markers CD3, CD4, CD8 as well as against CD79 alpha B cells. Ultrathin sections were examined under a transmission electron microscope. RESULTS: Autoimmune reaction in GD consisted of an increased number of CD4+ T cells (3.17±4.27%) and plasma cells (22.89±8.61%) producing thyroidstimulating hormone-receptors and stimulating thyrocytes to activity. The number of CD8+ T cells was increased in children with HT (20.54±0.68%) as compared with the controls (0.65±0.30%). The autoimmune reaction in the HT children showed antibody dependent cytotoxicity with a low number of CD4+ T cells and an increased number of CD8+ T cells in the thyroid tissue in comparison with that in the GD children and the controls. Plasma cells (31.65±9.11%) in this situation produced the antibodies involved in cytotoxic reactions against thyrocytes. CONCLUSIONS: Graves' disease is characterized by the increased number of CD4+ T cells and CD8+ T cells. Hashimoto's thyroiditis is characterized by the low number of CD4+ T cells and increased number of CD8+ T cells. CD8+ T cells have cytotoxic properties only in Hashimoto's thyroiditis.

Panhypopituitarism after multisystem trauma.

INTRODUCTION: The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. THE AIM OF THE STUDY: To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. CASE REPORT: A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. CONCLUSION: Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

Testicular adrenal rest tumours in boys with congenital adrenal hyperplasia: case report and literature review.

Nodular testicular lesions derived from adrenal tissue (testicular adrenal rest tumours - TART) in boys and men with congenital adrenal hyperplasia (CAH) lead to testicular structure damage, spermatogenesis disorders, and infertility. Hyperplasia of the ectopic adrenal tissue in testes is associated with high levels of the adrenocorticotropic hormone (ACTH) in blood serum. The development of non-invasive methods of diagnostic imaging allows detection of testicular lesions in adolescents and children. The basic method for TART detection is imaging with ultrasonography (USG) being the most widely available method. Since these mild testicular lesions can cause impaired fertility, periodic palpation and testicular ultrasonography should be performed in patients with CAH in order to prevent infertility.