RESUMO
PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. METHODS: We screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. RESULTS: We identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. CONCLUSION: SEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.
Assuntos
Hipogonadismo , Semaforinas , Moléculas de Adesão Celular , Células HEK293 , Humanos , Hipogonadismo/genética , Proteínas de Membrana , Proteínas do Tecido Nervoso/genética , Receptores de Superfície CelularRESUMO
BACKGROUND: Obesity is a worldwide epidemic. In recent years, increasing attention has been focused on thyroid function in obesity. OBJECTIVES: To establish the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents, and identify the relationship between TSH levels and other metabolic and hormonal variables before and after weight reduction. MATERIALS AND METHODS: We evaluated 150 obese subjects (aged 3-17 years) for anthropometric, biochemical, metabolic and hormonal variables. Measurements were taken at baseline and, in a subgroup of children with hyperthyrotropinemia, after a 6-month intervention program based on exercise, behavior therapy, and nutrition education. RESULTS: At baseline, 23 participants (15.3 %) had hyperthyrotropinemia, and 21 of these patients completed the weight reduction intervention. Among these 21 patients, 14 had substantial weight loss and a significant decrease in TSH and free T3 levels. CONCLUSION: We conclude that TSH and T3 levels are significantly increased in childhood obesity; in most cases, however, these increases cannot be elucidated by thyroid autoimmunity or iodine deficiency. If thyroid disorders are excluded beforehand, an elevated TSH with normal thyroid hormone levels in obese children seems rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated TSH levels. In this context, thyroid hormone alterations in obesity suggest an adaptation process.
Assuntos
Obesidade/sangue , Tireotropina/sangue , Redução de Peso , Adolescente , Peso Corporal , Criança , Pré-Escolar , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Obesidade/terapiaRESUMO
Conn syndrome, which is rarely encountered in children, is characterized by increased aldosterone, low renin level, and arterial hypertension. Severe complications, such as impaired vascular smooth muscle function secondary to increased aldosterone, endothelial dysfunction, deterioration of left ventricular functions, acute effects on the cardiovascular system, and proteinuria, may be observed. We present a case of primary aldosteronism in a patient who has been followed up for approximately 2 years. A 15-year-old girl complained of headache lasting for approximately 1.5 years, which was diagnosed as severe hypertension. All of her systemic examinations were normal other than the hypertension. Primary aldosteronism was diagnosed on the basis of hypokalemia and alkalosis accompanied by plasma renin activity of 3.9 ng/mL/h and an aldosterone level of 1007 pg/mL (normal: 40-480). Left adrenalectomy was performed because a 10x12x12 mm adenoma was detected on abdominal magnetic resonance imaging. Although aldosterone levels returned to normal values after the surgery, antihypertensive treatment was continued because of the persistent hypertension. As the 24-h ambulatory blood pressure values of the patient were normal at 10 months after the operation, the treatment was stopped, and she was followed up for 15 months without any treatment. Since then, she has been normotensive.
Assuntos
Hiperaldosteronismo/diagnóstico , Hipertensão/diagnóstico , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Hiperaldosteronismo/complicações , Hipertensão/etiologiaRESUMO
There are few reports of an association between Turner syndrome (TS) and 21-hydroxylase deficiency. However, this association is more frequent in some populations. The aim of this study was to evaluate the incidence of 21-hydroxylase deficiency in patients with TS in our population. 21-hydroxylase deficiency was evaluated in 44 TS cases with 45X (n=20) and 24 mosaic cases. A standard dose adrenocorticotropic (ACTH) stimulation test (Synacthen, Novartis, Basel, Switzerland) was performed, and 17 hydroxyprogesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS) and cortisol responses were evaluated. Patients with increased 17OHP responses in the stimulation test also underwent 21-hydroxylase gene analysis. The mean age was 14.6 +/- 4 (2.6-22.4); 37 patients were on growth hormone (GH) treatment. Nine patients were at prepubertal stage, whereas 35 were pubertal (24 on gonadal steroids and 11 spontaneously). Six patients were obese. Only one of our patients had a level of 7.5 ng/mL of 17OHP, and there was no mutation found in congenital adrenal hyperplasia (CAH) genetic analysis. In other cases, peak 17OHP levels were < or = 6 ng/mL. The mean peak 17OHP was 2.62 +/- 1.48 (1.19-7.5) ng/mL, the cortisol level was 37.6 +/- 8.43 (23.9-56.2) microg/dL and the DHEAS was 135.2+/- 87.3 (15-413) microg/dL. The increased mean basal and peak cortisol levels (20.5 +/- 10.2 and 37.6 +/- 8.4 microg/dL) were remarkable findings. Whereas basal cortisol was above 20 microg/dL in 38.7% of patients, exaggerated results up to 56.2 microg/dL were obtained in peak cortisol levels. The basal and peak 17OHP cortisol levels were not correlated with the presence of puberty, chromosome structure, gonadal steroid use, obesity or growth hormone use. This trial suggested that 21-hydroxylase deficiency was not common among patients with TS in our population. Adrenal function should be assessed, at least in the presence of clitoral enlargement in patients with TS, particularly if their karyotype does not contain a Y chromosome.
Assuntos
Glândulas Suprarrenais/fisiologia , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/fisiopatologia , Síndrome de Turner/complicações , Síndrome de Turner/fisiopatologia , 17-alfa-Hidroxiprogesterona/sangue , Adolescente , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hormônio Adrenocorticotrópico/sangue , Criança , Pré-Escolar , Análise Mutacional de DNA , Técnicas de Diagnóstico Endócrino , Feminino , Humanos , Hidrocortisona/sangue , Incidência , Esteroide 21-Hidroxilase/análise , Esteroide 21-Hidroxilase/genética , Síndrome de Turner/sangue , Síndrome de Turner/epidemiologia , Adulto JovemRESUMO
Congenital hypothyroidism (CH) is the most commonly encountered endocrinological birth defect, with an incidence of approximately 1 in 3000-4000 live births. It could be sporadic or familial as well as goitrous or non-goitrous. Inactivating mutations of TSHR , which is one of the genes responsible for non-goitrogenic congenital hypothyroidism, are mostly inherited autosomal recessively and result in a wide clinical spectrum owing to the extent of receptor function loss. Here, we report detailed clinical features of two CH cases with TSHR mutations. The first case was diagnosed before the initiation of the national screening program and had a severe clinical phenotype associated with a homozygous inactivating TSHR mutation (P556R), whereas the second case was diagnosed after the introduction of the national screening program and showed a mild clinical presentation and carried another homozygous missense mutation (P162A) in the TSHR gene. We compared the clinical features of our cases with those of previously reported patients with TSHR mutations to enhance the genotype/phenotype correlations between these mutations and corresponding clinical phenotypes.
Assuntos
Hipotireoidismo Congênito/diagnóstico , Mutação de Sentido Incorreto , Mutação Puntual , Receptores da Tireotropina/genética , Hipotireoidismo Congênito/tratamento farmacológico , Hipotireoidismo Congênito/genética , Análise Mutacional de DNA , Humanos , Lactente , Recém-Nascido , Masculino , Receptores da Tireotropina/metabolismo , Tiroxina/uso terapêuticoRESUMO
Thiamine-responsive megaloblastic anemia (TRMA) syndrome is an uncommon autosomal recessive disorder. The disease is caused by mutations in the gene, SLC19A2, encoding a high-affinity thiamine transporter, which disturbs the active thiamine uptake into cells. Major features include megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Cardiac malformations with conduction defects and/or dysrhythmias, have also been described in some patients. To our knowledge, only 13 TRMA patients with cardiac defects have been reported. Here, we describe the first case of TRMA syndrome with atrial standstill, probably caused by a 2 base-pair deletion in exon 4 (1147delGT) of the gene SLC19A2.
Assuntos
Arritmias Cardíacas/genética , Átrios do Coração/fisiopatologia , Proteínas de Membrana Transportadoras/genética , Anemia Megaloblástica/complicações , Anemia Megaloblástica/genética , Anemia Megaloblástica/fisiopatologia , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Criança , Diabetes Mellitus/genética , Diabetes Mellitus/fisiopatologia , Mutação da Fase de Leitura , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Complexo Cetoglutarato Desidrogenase/deficiência , Complexo Cetoglutarato Desidrogenase/genética , Masculino , Deficiência de Tiamina/congênitoRESUMO
Developing an effective and safe vaccine against Covid-19 will facilitate return to normal. Due to hesitation toward the vaccine, it is crucial to explore the acceptability of the COVID-19 vaccine to the public and healthcare workers. In this cross-sectional survey, we invited 2251 pediatricians and 506 (22%) of them responded survey and 424 (84%) gave either nasopharyngeal swap or antibody assay for COVID-19 and 71 (14%) of them got diagnosis of COVID-19. If the effective and safe COVID-19 vaccine was launched on market, 420 (83%) of pediatrician accepted to get vaccine shot, 422 (83%) of them recommended vaccination to their family members, 380 (75%) of them accepted to vaccine their children and 445 (85%) of them offered vaccination to their pediatric patients. Among the participated pediatricians 304 (60%) of them thought COVID-19 vaccine should be mandatory. We found that there are high COVID-19 vaccine willingness rates for pediatricians for themselves, their own children, family members and their pediatric patients. We also found that being a pediatric subspecialist, believing in achieving an effective vaccine, willingness to participate in the phase 1-2 clinical vaccine trial, willingness to get an influenza shot this season, believing a vaccine and vaccine passport should be mandatory were significant factors in accepting the vaccine. It is important to share all information about COVID-19 vaccines, especially effectiveness and safety, with the public in a clear communication and transparency. The opposite will contribute to vaccine hesitancy and anti-vaccine movement.
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Vacinas contra COVID-19 , COVID-19 , Criança , Estudos Transversais , Humanos , Pediatras , SARS-CoV-2 , Turquia , VacinaçãoRESUMO
PURPOSE: To compare crystalline lens density in obese and nonobese children. METHODS: A total of 40 obese (25 females) and 46 age-sex matched controls (26 females) were included in this prospective study. Children with ocular diseases (except for mild refractive errors), ocular trauma, or surgery and any systemic disorders, including diabetes, were excluded. Lens densitometry (LD), central corneal thickness (CCT), anterior chamber depth (ACD) and corneal volume (CV) were measured by Pentacam HR. RESULTS: Mean participant age was 12.0 ± 1.9 (range, 7.2-18 years) in the obese group and 11.7 ± 2.0 (range, 7.5-16.1 years) in the control group. The BMI was 29.9 ± 4.5 in the obese group and 18.7 ± 2.5 in the control group (P ≤ 0.05). The vertical, horizontal, and areal lens density measurements were higher in obese group than in controls (P ≤ 0.05). There was a positive correlation between BMI and vertical, horizontal, and areal lens density measurements. The difference in CCT, ACD, and CV was not statistically significant between groups (P ≥ 0.05). CONCLUSIONS: There is increased lens density in the obese children compared with controls. Pentacam HR may provide objective data about lens density in children.
Assuntos
Cristalino/patologia , Obesidade Infantil/complicações , Adolescente , Câmara Anterior/patologia , Índice de Massa Corporal , Criança , Córnea/patologia , Densitometria/métodos , Feminino , Humanos , Masculino , Fotografação/métodos , Estudos ProspectivosRESUMO
BACKGROUND: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. METHODS: A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. RESULTS: We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. CONCLUSIONS: This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.
Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Testes Genéticos/métodos , Quinases do Centro Germinativo , Fator 1-alfa Nuclear de Hepatócito , Humanos , Lactente , Masculino , Fenótipo , Prognóstico , Proteínas Serina-Treonina Quinases , Turquia , Adulto JovemRESUMO
CONTEXT: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. OBJECTIVE: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. DESIGN: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. SETTING: The study was conducted in 19 tertiary pediatric endocrinology clinics. PATIENTS: Ninety-five children (48 females, aged 0-18 y, eight familial) with PAI of unknown etiology participated in the study. RESULTS: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged. CONCLUSION: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.
Assuntos
Insuficiência Adrenal/etiologia , Insuficiência Adrenal/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , DNA/genética , Feminino , Expressão Gênica/genética , Variação Genética/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/genética , Turquia/epidemiologiaRESUMO
Objective. GnRH analogues (GnRHa) are used in the treatment of central precocious puberty (CPP). The purpose of this study was to evaluate the efficacy of treatment with a GnRHa (leuprolide acetate) in patients with CPP. Subjects and Methods. A total of 62 female child patients who had been diagnosed with CPP, rapidly progressive precocious puberty (RP-PP), or advanced puberty (AP) and started on GnRHa treatment (leuprolide acetate, Lucrin depot, 3.75 mg once every 28 days) were included in the study. The efficacy of treatment was evaluated with anthropometric data obtained, progression of pubertal symptoms observed, as well as GnRHa tests, and, when necessary, intravenous GnRH tests carried out in physical examinations that were performed once every 3 months. Results. In the current study, treatment of early/advanced puberty at a dose of 3.75 mg once every 28 days resulted in the suppression of the HHG axis in 85.5% of the patients. Conclusion. The findings of this study revealed that a high starting dose of leuprolide acetate may not be necessary in every patient for the treatment of CPP. Starting at a dose of 3.75 mg once every 28 days and increasing it with regard to findings in follow-ups would be a better approach.
RESUMO
INTRODUCTION AND PURPOSE: This study aims to investigate the effect of Gonadotropin-releasing hormone analogues (GnRHa) treatment on anterior pituitary hormones in female children with central precocious puberty (CPP). SUBJECTS AND METHOD: There were 62 female children who had been diagnosed with CPP and received GnRHa (Leuprolide acetate, 3.75 mg intramuscular/subcutaneous/28 days) included in the study. All subjects were clinically evaluated prior to treatment and every 3 months during treatment with serum LH, FSH, ACTH, TSH, PRL as pituitary hormones, and the end hormones such as plasma E2, cortisol, fT3, fT4 levels were measured. IGF-1 and IGFBP-3 levels were measured, and SDS was evaluated according to age and gender. RESULTS: Prolactin levels were higher during GnRHa treatment compared to pre-treatment values although the increase was statistically significant only at month 3. In addition, while 2 (3.2%) of the patients had hyperprolactinemia before treatment, 11 (17.7%) patients developed hyperprolactinemia at different time points during treatment. CONCLUSION: This study concluded that GnRHa treatment resulted in hyperprolactinemia and had no significant effect other pituitary hormones.
Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio do Crescimento Humano/sangue , Leuprolida/uso terapêutico , Hormônio Luteinizante/sangue , Prolactina/sangue , Puberdade Precoce/tratamento farmacológico , Tireotropina/sangue , Criança , Pré-Escolar , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Puberdade Precoce/sangue , Resultado do TratamentoRESUMO
The most common congenital endocrine disorder is congenital hypothyroidism (CH), which can lead to mental retardation if untreated. Majority of the patients have been found to have defects in thyroid development and migration disorders (dysgenesis), and the remaining ones have thyroid hormone synthesis defects (dyshormonogenesis). One of the most common mechanisms to cause dyshormonogenesis is a defect in the thyroid peroxidase (TPO) enzyme. In familial cases, mutations in the TPO gene are fairly prevalent. To date, more than 80 mutations have been identified, which result in variably decreasing TPO bioactivities. Clinical manifestations of TPO defects are typically permanent CH and with or without goiter. In this report, we presented two children with CH who were born to consanguineous parents and were homozygous carriers of a missense (G319R) TPO mutation, the mutation segregated with the disease status in the families confirming its pathogenicity. G319R mutation seemed to be a common cause of CH in Turkish population, which could originate from a common founder ancestor. Moreover, our results also confirmed the phenotypic variability associated with different TPO mutations.
Assuntos
Hipotireoidismo Congênito/genética , Efeito Fundador , Iodeto Peroxidase/genética , Mutação de Sentido Incorreto , Consanguinidade , Humanos , Lactente , Recém-Nascido , Masculino , Repetições de Microssatélites/genética , TurquiaRESUMO
OBJECTIVE: To investigate serum asymmetric dimethylarginine (ADMA) levels in children with isolated growth hormone deficiency (GHD) and to determine the effect of GH replacement therapy on these levels. METHODS: 31 patients diagnosed with isolated GHD and 29 age-and sex-matched healthy children were enrolled in the study. Height, weight and waist circumference were measured in all subjects. Fasting serum insulin-like growth factor-1 (IGF-1), IGF binding protein-3, glucose, insulin and lipid levels were evaluated. Serum ADMA levels were assessed using the enzyme-linked immunosorbent assay technique. The same evaluations were repeated on the 3rd and 6th months of treatment in 28 of the GHD cases. RESULTS: There were no significant differences in ADMA levels between the patient and control groups [0.513±0.130 (0.291-0.820) µmol/L vs. 0.573±0.199 (0.241-1.049) µmol/L]. There was a positive correlation between serum ADMA and HbA1c levels in the control group. In the GHD cases, ADMA levels negatively correlated with high-density lipoprotein levels and positively correlated with low-density lipoprotein levels. There was also a significant increase in ADMA levels in patients receiving GH therapy compared to pre-treatment levels [serum ADMA level, 1.075±0.133 (0.796-1.303) µmol/L at the 3rd month and 0.923±0.121 (0.695-1.159) µmol/L at the 6th month of treatment]. There was a negative correlation between ADMA levels and homeostasis model assessment of insulin resistance values at the 6th month evaluation. There were no relationships between ADMA levels and age, sex, or pubertal state either before or during the treatment. CONCLUSION: Serum ADMA levels were found to be similar in patients with GHD and in healthy children. However, serum ADMA levels showed a significant increase in GHD patients following GH replacement therapy.
Assuntos
Arginina/análogos & derivados , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/deficiência , Adolescente , Arginina/sangue , Biomarcadores , Glicemia/metabolismo , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , PrognósticoRESUMO
Rett syndrome is an X-linked dominant disorder frequently caused by the mutations in the methyl-CpG-binding protein 2 gene (MECP2). Its prevalence in the population is 1/15,000-20,000. Patients with Rett syndrome present apparently normal psychomotor developments during the first 6-18 months of life. Subsequently, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. Precocious puberty is characterized by premature breast and pubic hair development, and advanced bone age development at 8 years of age. We present a case of Rett syndrome and precocious puberty in a 6-year-old girl. At the age of 6, the first signs of precocious puberty appeared (Tanner stage 3). Laboratory measurements were detected as follows: luteinizing hormone (LH), 0.2 mIU/mL; follicle-stimulating hormone (FSH), 1.1 mIU/mL; estradiol, 36 pg/mL; bone age, 9 years. The response to luteinizing hormone releasing hormone (gonadotropin-releasing hormone stimulation test) was characteristic for true precocious puberty (LH, 32 mIU/mL; FSH, 26 mIU/mL). This is the first reported case of precocious puberty related to Rett syndrome.
Assuntos
Puberdade Precoce/etiologia , Síndrome de Rett/fisiopatologia , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Progressão da Doença , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Proteína 2 de Ligação a Metil-CpG/genética , Mutação de Sentido Incorreto , Osteoporose/etiologia , Puberdade Precoce/tratamento farmacológico , Puberdade Precoce/metabolismo , Síndrome de Rett/genética , Resultado do TratamentoRESUMO
There are different opinions concerning changes in glucose metabolism in patients with Laron syndrome. In this paper we discuss the treatment results of our patient with Laron syndrome who developed diabetes during late adolescence. A 19-year-old boy with Laron syndrome was referred to our clinic for follow-up. He had been diagnosed with Laron syndrome (LS) at 4 years old and rIGF-1 therapy was initiated. After 4 months the treatment was discontinued. At the age of 17, rIGF-1 therapy was restarted. A height gain of 8.8 cm. was observed during the 2-year treatment period. He was admitted to our hospital at the age of 19 years following discontinuation of the therapy. At that time, his height was 142 cm, and weight for height was 136%. His blood glucose was 85 mg/dL (4.72 mmol/L), insulin was 26.39 pmol/L, and HbA1c was 5.4%. At the age of 20, when he has not been receiving IGF-1 therapy for 1 year, his weight for height was 143 cm. Laboratory evaluation revealed that fasting blood glucose was 176 mg/dL (9.77 mmol/L), fasting insulin was 29.86 pmol/L, and HbA1c was 7.5%. Primary insulin therapy was then initiated. His parents both had a diagnosis of type 2 diabetes. Insulin therapy was switched to oral antidiabetic (OAD) therapy at the end of the second year because of a normal C-peptide level of 0.8 nmol/L under insulin therapy. After 6 months of OAD, HbA1c was 5.7%. The treatment was then switched to IGF-1 therapy, but his blood glucose profile was impaired and OAD therapy was restarted. In conclusion, we observed that genetic susceptibility and abdominal obesity caused type 2 diabetes in this patient. We believe that oral antidiabetic agents and life-style changes may be the appropriate approach when diabetes is developed in LS patients.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Síndrome de Laron/fisiopatologia , Obesidade Abdominal/fisiopatologia , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suscetibilidade a Doenças , Monitoramento de Medicamentos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/uso terapêutico , Síndrome de Laron/complicações , Síndrome de Laron/tratamento farmacológico , Masculino , Metformina/uso terapêutico , Obesidade Abdominal/complicações , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Hyperinsulinemic hypoglycemia (HIH) is a genetically heterogeneous disorder with both familial and sporadic variants. Patients with HIH may present during the neonatal period, infancy, or childhood and may show transient, prolonged, and persistent features. In this study, we aimed to discuss our experience with HIH patients, based on a series of 17 patients. METHODS: We retrospectively analyzed the clinical and laboratory characteristics at the time of diagnosis and during treatment and evaluated the neurodevelopmental outcomes during follow-up in 17 HIH patients, who presented or were referred to the Pediatric Endocrinology Clinic of Dr. Sami Ulus Training and Research Children's Hospital between 1998 and 2011. The patients (7 male, 10 female) were aged between the first day of life and 7 years - 10 were in their first week of life, 6 in their infancy, and 1 in childhood. RESULTS: None of the mothers had gestational diabetes. Hypoglycemic seizure (76.5%) was the most common presenting symptom. Medical treatment failed in two patients, and was stopped in eight patients. Of two diazoxide-unresponsive patients, one underwent near-total pancreatectomy, but hypoglycaemic episodes continued after surgery. The parents of other patient refused surgery, the medical treatment was continued, nevertheless, severe motor and mental retardation developed. At follow-up, 23.5% of the patients were found to have mild or moderate psychomotor retardation, and 23.5% developed epilepsy. There was no marked difference in neurological results between cases with onset in the neonatal period or in infancy. CONCLUSIONS: Clinical course and treatment response in HIH cases are very heterogeneous. Long-term careful monitoring is needed to detect and treat the complications.
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Hiperinsulinismo/complicações , Hipoglicemia/complicações , Criança , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Diazóxido/uso terapêutico , Epilepsia/etiologia , Feminino , Humanos , Hiperinsulinismo/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Lactente , Recém-Nascido , Deficiência Intelectual/etiologia , Masculino , Estudos RetrospectivosRESUMO
Cushing's disease is a condition in which hypercortisolism develops due to excessive hypophyseal adrenocorticotropic hormone production. It is rare in childhood. In this paper, we report the case of a 10-year-old male patient with hypophyseal microadenoma-related Cushing's disease who presented with obesity and was found to show poor height growth at follow-up. The diagnosis was confirmed with inferior petrosal sinus sampling, and the adenoma was successfully removed by transsphenoidal surgery. While adrenal axis suppression continued for approximately 1 year, clinical improvement was clearly observed after the third month following surgery. The findings in this patient demonstrate that decreased growth rate despite rapid weight gain in children can be early sign of Cushing's disease and emphasize the importance of monitoring of growth in obese children.
Assuntos
Adenoma/diagnóstico , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/diagnóstico , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/sangue , Criança , Ritmo Circadiano , Dexametasona , Seguimentos , Humanos , Hidrocortisona/sangue , Masculino , Amostragem do Seio Petroso , Neoplasias Hipofisárias/cirurgiaRESUMO
OBJECTIVE: Training teachers and education professionals on diabetes is crucial for full-time monitoring of diabetic children in schools. The objective of this study was to assess the knowledge on diabetes in a group of school teachers in Turkey. METHODS: Between November 2010 and November 2011, 1054 teachers from three regions of Ankara were given a questionnaire to assess their knowledge on diabetes. The mean age of the group (27% males, 73% females) was 38.8±8 years. 61.7% of the participants were class teachers, 23.3% were school counselors, and the rest were physical education teachers and administrators. RESULTS: A fair percentage (47.6%) of the participants had a moderate knowledge level on diabetes and 32.4% expressed a lower level of knowledge. A large proportion (94%) gave an accurate definition of diabetes. Of the total group of 1054 teachers, 625 were aware that blood glucose level might decrease in diabetic children during follow-up. Also, 75% believed that diabetic children were eligible for physical education classes. 52.8% of these teachers had no diabetic child in their classes and teachers with a diabetic patient in their family had better knowledge of diabetes compared to their counterparts. CONCLUSIONS: Our study results indicate that school teachers have limited knowledge on diabetes. We believe that their knowledge levels can be improved by widespread training programs.
Assuntos
Diabetes Mellitus Tipo 1/terapia , Promoção da Saúde , Adulto , Aconselhamento/educação , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Docentes , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipoglicemia/prevenção & controle , Internet , Masculino , Pessoa de Meia-Idade , Apoio Social , Inquéritos e Questionários , Turquia , Recursos Humanos , Adulto JovemRESUMO
A combination of Turner syndrome (TS) and classical congenital adrenal hyperplasia (CAH) is rare. A one-day-old newborn was referred to our hospital with ambiguous genitalia. The parents were third-degree relatives. The infant's weight was 3350g (50-75p), and the head circumference was 34.5cm (50p). The gonads were nonpalpable. Presence of a 3 cm phallus, one urogenital opening into the perineum, and incomplete labial fusion were identified. Laboratory tests revealed a classical type of CAH due to 21-hydroxylase deficiency. Karyotyping revealed a 45X0(35)/46XX(22) pattern with negative sex-determining region Y (SRY) on gene analysis. At the most recent follow-up visit, the patient appeared to be in good health - her height was 70.4 cm [-1.5 standard deviation (SD)] and her weight was 9.8 kg (0.3 SD). She was receiving hydrocortisone in a dose of 10 mg/m²/day, fludrocortisone acetate in a dose of 0.075 mg/day, and oral salt of 1 g/day. System examinations were normal. The patient's electrolyte levels were found to be normal and she was in good metabolic control. The findings of this patient demonstrate that routine karyotyping during investigation of patients with sexual differentiation disorders can reveal TS. Additionally, signs of virilism should always be investigated at diagnosis or during physical examinations for follow-up of TS cases. SRY analysis should be performed primarily when signs of virilism are observed. CAH should also be considered in patients with negative SRY.