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BACKGROUND: Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKI's), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor1 (IGF-1). OBJECTIVE: The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML. METHODS: English-language publications were searched in the PubMed/Cochrane library/Google Scholar databases (2002-2023), and retrieved studies were assessed according to PRISMA-Statement and Newcastle- Ottawa-scale. RESULTS: The search strategy yielded 1066 articles. After applying the inclusion/exclusion criteria, 941 were excluded based on title screening and 111 on abstract review. The systematic review included 14 articles (11 retrospective observational studies/3 clinical trials). Twelve studies reported data on the prevalence of growth disorders after the administration of 1st generation TKIs (imatinib). Two studies reported a negative effect of 2nd generation TKIs (dasatinib/nilotinib) on physical growth. Four studies recorded a decrease in height z-score after treatment compared to baseline. Two 1st-generation TKIs studies reported data on children's final height; one reported restoration of final height to normal after the onset of puberty, despite initial slowing, and the final height was lower than mid-parental target height. Serum IGF-1 levels were reported in 2 studies to be within normal range, while in 3 studies, a significant decrease was documented. Considerable study heterogeneity was observed related to dosage/duration of treatment/disease phase/stage of puberty/ethnicity. CONCLUSION: A negative effect of TKIs on the growth and final height of children was noted.
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Background: Thyroid surgery in pediatric population is not as common as that in adults, although they share the same indications, techniques and complications. This review aims to evaluate the surgical management of thyroid disease in patients under 18 years old. Methods: We conducted a bibliographic search in the international literature. Data from the identified studies such as demographics, indication for surgery, type of procedure, complications and length of hospital stay were recorded. A retrospective review study of all patients under 18 years old who underwent thyroidectomy was performed. Results: We included 37 retrospective studies and a total of 12,728 patients. Thyroidectomy was more common in female patients and the mean age was approximately 14 years old. The leading indication for surgery was benign thyroid pathology. Due to the surgical treatments' safety and effectiveness in young patients, total and subtotal thyroidectomy, whether for malignancies or benign diseases, is becoming more popular today. The most often occurring complication of pediatric thyroid surgery is hypoparathyroidism. Despite the high likelihood of recurrence of pediatric malignancies, overall survival rates of pediatric thyroid cancer are excellent. Conclusions: Thyroidectomy performed by high-volume thyroid surgeons in children and adolescents is considered an efficient and safe method of treatment of thyroid disease.
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BACKGROUND: Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes. PROCEDURE: We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls. RESULTS: The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence). CONCLUSIONS: Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.
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Apolipoproteínas E , Lipídeos , Lipase Lipoproteica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Apolipoproteínas E/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Criança , Masculino , Feminino , Lipase Lipoproteica/genética , Pré-Escolar , Lipídeos/sangue , Adolescente , Polimorfismo de Nucleotídeo Único , Genótipo , Alelos , Asparaginase/administração & dosagem , Asparaginase/uso terapêutico , Asparaginase/efeitos adversos , Polimorfismo GenéticoRESUMO
MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2 prognostic factors. Higher expression levels of let-7c-5p, miR-106b-5p, miR-26a-5p, miR-155-5p, miR-191-5p, miR-30b-5p and miR-31-5p were significantly associated with a good prednisone response. The expression levels of miR-125b-5p, miR-150-5p and miR-99a-5p were significantly higher in standard- or intermediate-risk patients compared with those in high-risk patients (P=0.017, P=0.033 and P=0.017, respectively), as well as in those with a complete response at the end of induction (P=0.044 for all three miRNAs). The change in expression levels between diagnosis and the end of induction differed significantly between risk groups for three miRNAs: miR-206, miR-210 and miR-99a (P=0.033, P=0.047 and P=0.008, respectively), with the post induction levels of miR-206 increased in high-risk patients, whilst miR-210 and miR-99a levels were increased in intermediate/standard risk patients. Therefore, miRNAs that could be integrated into the risk stratification of pediatric ALL after further evaluation in larger patient cohorts were identified.
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Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with hematological malignancies. Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. CRP, PSP, and MR-proADM levels were measured at the onset of the febrile episode (day 1), day 3, and day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as an area under a receiver operating characteristic (ROC) curve. ROC curves were used for each biomarker to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis. Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with hematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%), a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers on day 1 differed significantly between patients with and without sepsis. PSP, MR-proADM, and CRP specificity were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM, and CRP were 0.84, 0.74, and 0.88, respectively. Conclusions: PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with hematological malignancies. However, PSP has a higher sensitivity and specificity.
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AIMS: To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece. METHODS: Boys with T1DM visited the Outpatient Clinics of the 1st and 2nd Department of Paediatrics of Aristotle University of Thessaloniki from March until June 2022 were enrolled. Recent anthropometric data were recorded during the follow-up visit whereas previous anthropometric data and demographic data were collected from medical files. A volume of testis > 3 ml was indicative for the onset of puberty. RESULTS: A total of 46 boys with T1DM with documented pubertal onset after the diagnosis of T1DM were included in the study. Precocious puberty (<9 years old) was recorded in 5 boys (10.2 %), early puberty (<10 years but >9 years) in 10 (20.4 %) and 34 (69.4 %) entered puberty normally. The duration of T1DM was inversely correlated to the likelihood of earlier puberty (P < 0.001). However, no notable year predominance was observed suggesting no COVID-19 effect. CONCLUSION: A considerable number of Greek boys with T1DM appear to develop precocious and early puberty, raising thoughts regarding diabetes management and other possible cofactors.
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Diabetes Mellitus Tipo 1 , Puberdade Precoce , Masculino , Humanos , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Puberdade , Testículo , Puberdade Precoce/epidemiologia , Puberdade Precoce/diagnóstico , AntropometriaRESUMO
Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis.
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Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, p = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.
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Aim of this study was to evaluate the long-term therapeutic outcome and treatment-related complications in Hodgkin disease. We reviewed the medical records of 93 patients diagnosed with classic Hodgkin lymphoma, treated, and followed-up during the last 25 years. The cohort study included 49 males and 44 females with median age 11.8 years old (range: 3.95 to 17.42 y). The most common subtype was nodular sclerosis in 47/93 (50.5%). B symptoms were present in 15/93 (16.1%). From January 2009 until December 2020, 55 (59%) patients diagnosed with Hodgkin lymphoma were treated according to European Network for Pediatric Hodgkin Lymphoma (EURONET)-PHL-C1 protocol. Concerning outcome, a total of 89/93 patients are alive. Relapse occurred in 7/93. Second malignancies are reported in a total of 5 patients, 3 solid tumors (thyroid cancer, breast cancer, and osteosarcoma), and 2 acute myeloid leukemias. The overall survival and event-free survival for the whole cohort were 95.7% and 83.9%, respectively. Disease-free survival was 92.5%. Although a considerable high fraction of patients with Hodgkin disease can achieve continuous complete remission, they are at a high risk of developing long-term treatment-related complications. High curative rates as well as prevention of late effects can be achieved by implementation of individualized treatment strategies and innovative treatments.
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Doença de Hodgkin , Masculino , Feminino , Humanos , Criança , Adolescente , Doença de Hodgkin/terapia , Doença de Hodgkin/tratamento farmacológico , Seguimentos , Grécia/epidemiologia , Estudos de Coortes , Taxa de Sobrevida , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND/AIM: Infections are a major cause of morbidity and mortality in children with haematologic malignancies and solid tumors as well as those undergoing hematopoietic stem cell transplantation (HSCT). The purpose of our study was to record the epidemiological characteristics and outcomes of bacteremias, focusing on pathogens, as well as risk factors and mortality rates in patients of a pediatric hematology-oncology unit from Northern Greece. MATERIALS AND METHODS: A retrospective analysis was conducted, which included all positive blood cultures from pediatric hematology oncology patients aged from 1 to 16 years old admitted to the Pediatric and Adolescent Hematology Oncology Unit of AHEPA University Hospital of Thessaloniki between January 2014 and December 2018. Data were collected from patients' printed and electronic medical records. RESULTS: 73 episodes of bacteremias were identified (41% male and 32% female with a ratio of 1.28:1; median age 6.5 years; 13.7% solid tumor, 72.6% acute lymphoblastic leukemia, 13.7% acute myeloid leukemia, and 95.8% with an indwelling permanent catheter). 49.3% of the isolates were Gram-positive bacteria and 50.7% Gram-negative, and the ratio of Gram-negative to Grampositive was 1.02. Coagulase-negative staphylococci were most frequent (39.7%), followed by E. coli (17.8%) and Klebsiella pneumoniae (17.8%). Out of all Gram-negatives, 13.5% carbapenemase producers and 8.1% ESBL-producers were found. In relation to Gram-positive, 79.3% were identified as methicillin-resistant CoNS. During the study period, 10.9% of indwelling catheters were removed, and 2.73% of episodes resulted in ICU transfer. The 3-month mortality rate was 8.2%. CONCLUSION: This study demonstrated an almost equal distribution of Gram-positive and Gramnegative bacteremias in total in this population but with an increase in the isolation of Grampositive bacteria over the last years, which is consistent with other similar studies in this patient group. Knowledge of the local epidemiology and bacterial antimicrobial resistance is important to prevent and timely treat these life-threatening infections in immunocompromised pediatric oncology patients.
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Bacteriemia , Hematologia , Neoplasias , Adolescente , Humanos , Criança , Masculino , Feminino , Lactente , Pré-Escolar , Estudos Retrospectivos , Escherichia coli , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Fatores de Risco , AntibacterianosRESUMO
Pseudohypoparathyroidism type 1A (PHP1A) is a rare disease caused by molecular defects in the maternally-inherited allele of the guanine nucleotide-binding protein, α-stimulating (GNAS) gene. The GNAS gene encodes the stimulatory G-protein α-subunit that regulates production of the second messenger cyclic adenosine monophosphate. Heterozygous inactivating mutations in these specific loci are responsible for a spectrum of phenotypic characteristics of the disease, including clinical features of the Albright's hereditary osteodystrophy, due to resistance to parathyroid hormone (PTH). We report a case of PHP1A and explore the underlying novel point mutation of the GNAS gene that leads to an atypical PHP1A phenotype. A male patient with a round face, short stature, and brachydactyly accompanied by normocalcaemia and mild PTH resistance consulted at our center. The GNAS encoding region from the patient and both of his parents were amplified and sequenced directly in a sample of peripheral blood leukocytes. A novel c.389A>G point mutation in exon 5 of the GNAS gene, resulting in a p.Tyr130Cys peptidic chain change of the Gsα protein, detected in the proband, in heterozygous state. Sequencing of the GNAS gene from his parents did not reveal the c.389A>G mutation, confirming a de novo proband genotype. The maternal origin of the affected GNAS allele, along with mild PTH resistance, confirmed the PHP1A diagnosis. PHP1A, caused by inactivating GNAS mutations, presents a range of complex clinical phenotypes. The novel c.389A>G GNAS mutation presented in this case expands the spectrum of known PHP1A molecular defects and describes the associated phenotype.
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BACKGROUND: Alpha-subunit of the interleukin-2 receptor (IL2RA) is involved in the regulation of T-cell function and has been related to autoimmune thyroid disease (AITD). Although the exact mechanisms are not fully understood, promoter methylation might account for differences in gene expression. The aim of this study was to investigate whether there are differences in the percentage of DNA methylation within the IL2RA gene promoter in young patients with AITD. MATERIALS AND METHODS: In a cross-sectional design, the presence of DNA methylation in the IL2RA gene promoter was quantified, by real-time PCR and melting curve analysis, in modified genomic DNA isolated from blood samples of a total of 149 children and adolescents with AITD, including patients with Hashimoto thyroiditis (ΗΤ) (n = 60), Graves' disease (GD) (n = 9), concurrent diagnosis of HT and type 1 diabetes (T1DM + HT) (n = 25), and healthy controls (n = 55). RESULTS: The percentage of DNA methylation in the IL2RA gene promoter was significantly decreased in patients with GD (26.0 ± 4.2%) but not in those with HT (36.3 ± 1.4%) in comparison with controls (41.3 ± 1.5%). CONCLUSIONS: The observed DNA hypomethylation in the IL2RA gene promoter in patients with GD might be related to its increased expression, thus contributing to the etiopathogenesis of GD in childhood and adolescence.
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Metilação de DNA , Subunidade alfa de Receptor de Interleucina-2/genética , Tireoidite Autoimune/genética , Criança , Feminino , Humanos , Masculino , Regiões Promotoras GenéticasRESUMO
BACKGROUND: Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence the OPG/RANK/RANKL signaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age. METHODS: Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender. RESULTS: Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls. CONCLUSIONS: Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.
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Diabetes Mellitus Tipo 1/sangue , Osteoprotegerina/sangue , Hormônio Paratireóideo/sangue , Ligante RANK/sangue , Receptor Ativador de Fator Nuclear kappa-B/sangue , Vitamina D/sangue , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Prognóstico , Valores de ReferênciaRESUMO
WHAT IS KNOWN AND OBJECTIVE: Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 µg daily as l-selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT. METHODS: Seventy-one (71) children and adolescents, with a mean age of 11.3 ± 0.3 years (range 4.5-17.8), diagnosed with AT (antibodies against thyroid peroxidase [anti-TPO] and/or thyroglobulin [anti-Tg] ≥60 IU/mL, euthyroidism or treated hypothyroidism and goitre in thyroid gland ultrasonography) were randomized to receive 200 µg l-selenomethionine or placebo daily for 6 months. Blood samples were drawn for measurement of serum fT4, TSH, anti-TPO and anti-Tg levels, and thyroid gland ultrasonography was performed at the entry to the study and after 6 months of treatment. RESULTS AND DISCUSSION: At the end of the study, a statistically significantly higher reduction in anti-Tg levels was observed in the Se group compared to the placebo group (Δ: -70.9 ± 22.1 vs -6.7 ± 60.6 IU/mL, P = 0.021). Although anti-TPO levels were also decreased in the Se group, this change was not statistically different from that of the control group (Δ: -116.2 ± 68.4 vs +262.8 ± 255.5 IU/mL, P = 0.219). No significant difference in thyroid gland volume was observed between the two study groups (P > 0.05). WHAT IS NEW AND CONCLUSION: In this original study, organic Se supplementation appears to reduce anti-Tg levels in children and adolescents with AT.
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Suplementos Nutricionais , Selenometionina/administração & dosagem , Tireoidite Autoimune/terapia , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Glândula Tireoide/imunologia , Glândula Tireoide/fisiopatologia , Tireoidite Autoimune/fisiopatologia , Resultado do TratamentoRESUMO
Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). MATERIAL AND METHODS: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. RESULTS: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. CONCLUSIONS: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.
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Resistência à Insulina , Osteoprotegerina/sangue , Obesidade Infantil/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder that usually presents clinically as adrenal insufficiency in early infancy. It is caused by mutations in the NR0B1 gene which is located on the short arm of chromosome X (Xp21). The NR0B1 gene plays an important role in normal development and function of both the adrenal and gonadal axes and some patients with the disease can present in adolescence with hypogonadotropic hypogonadism. Testicular microlithiasis is an ultrasonographic finding of unknown etiology that has been associated with several benign conditions such as cryptorchidism, congenital adrenal hyperplasia, varicoceles, and testicular malignancy. We report the case of an 11-year-old boy who was diagnosed at the age of 8 months with X-linked AHC due to adrenal failure and presented testicular microlithiasis during follow-up. To the best of our knowledge, this is the first case of an X-linked AHC patient diagnosed with testicular microlithiasis in follow-up.
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Congenital isolated growth hormone deficiency (IGHD) type 1b is an autosomal recessive genetic condition caused by mutations of growth hormone (GH)-1 or the growth hormone releasing hormone receptor (GHRH-R) genes. Affected subjects present with symptoms of growth hormone deficiency (GHD) with low but detectable levels of growth hormone (GH), short stature and responsiveness to GH therapy. We describe a 13-month old girl with severe growth failure who showed a low GH response to two GH provocation tests and a modest increase of insulin-like growth factor-1 (IGF-1) to an IGF-1 generation test. Whole exome sequencing revealed a novel homozygous variant of the GHRH-R gene (c.97C>T), leading to a premature stop codon. Administration of recombinant human GH improved linear growth. This is the first report of a c.97C>T mutation of the GHRH-R gene.
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Nanismo/genética , Doenças da Hipófise/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Códon sem Sentido , Feminino , Humanos , LactenteRESUMO
Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that results from the clonal multiplication and accumulation of immature dendritic Langerhans cells. Its reported incidence rate varies, but is considered to be 2.6-8.9 per million children who are <15 years of age each year. It may affect any system or organ. The present study reported 4 pediatric LCH cases in order to highlight the heterogeneity of the initial presentation, and the pitfalls that may mislead clinicians and delay diagnosis. The clinical features, as well as the pathognomonic imaging, pathology findings and treatment options were presented. LCH may be rare, but it should always be included in the differential diagnosis of persistent eczema, unexplained skin lesions, diabetes insipidus and persistent bone pain, among others. While the debate on pathogenesis and treatment is ongoing, high index of suspicion among pediatricians, pediatric oncologists and other specialists (pathologists, dermatologists, orthopaedic surgeons, general practitioners or family physicians) is essential for early diagnosis, and optimal outcome.
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17-beta hydroxysteroid dehydrogenase type 3 (17ßHSD-3) enzyme catalyzes the conversion of androstenedione (Δ4) to testosterone (T) in the testes of the developing fetus, thus playing a crucial role in the differentiation of the gonads and in establishing the male sex phenotype. Any mutation in the encoding gene (HSD17B3) can lead to varying degrees of undervirilization of the affected male, ranging from completely undervirilized external female genitalia to predominantly male with micropenis and hypospadias. We present here an infant who was referred to our clinic because of ambiguous genitalia at birth. Gonads were palpable in the inguinal canal bilaterally and no Müllerian structures were identified on pelvic ultrasound. Because of a low T/Δ4 ratio after a human chorionic gonadotropin stimulation test, a tentative diagnosis of 17ßHSD-3 deficiency was made which was confirmed after genetic analysis of the HSD17B3 gene of the patient. The molecular analysis identified compound heterozygosity of two previously described mutations and could offer some further validation for the idea of a founder effect for 655-1;GâA mutation in the Greek population.
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17-Hidroxiesteroide Desidrogenases/deficiência , Transtorno 46,XY do Desenvolvimento Sexual , Ginecomastia , Erros Inatos do Metabolismo de Esteroides , 17-Hidroxiesteroide Desidrogenases/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtorno 46,XY do Desenvolvimento Sexual/metabolismo , Grécia , Ginecomastia/diagnóstico , Ginecomastia/genética , Ginecomastia/metabolismo , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo de Esteroides/diagnóstico , Erros Inatos do Metabolismo de Esteroides/genética , Erros Inatos do Metabolismo de Esteroides/metabolismoRESUMO
Nocturnal enuresis is a common symptom in children. It is usually attributed to benign causes and diagnostic evaluation is not carried out. We report three male young patients initially presenting with short stature and nocturnal enuresis, related to diabetes insipidus, caused by intracranial germinomatous germ cell tumors. In all three cases, water deprivation tests confirmed diabetes insipidus. Extensive endocrinological investigation also showed further hormone deficiencies. Magnetic resonance imaging of the brain revealed the presence of a central nervous system lesion and histology confirmed the final diagnosis. Surgery, radiation with or without chemotherapy was conducted and the patients were treated with hormone replacement therapies. The patients after a long follow-up were free of disease. We present these cases to alert clinicians to bear in mind that the presence of an intracranial germinomatous germ cell tumor should at least be considered in a child presenting with bed wetting, especially if additional symptoms and signs, including late onset puberty and growth delay or morning hypernatremia, may coexist.