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Objective: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes. To date, mutations have been identified in 14 different genes of patients with a clinical diagnosis of MODY. This study screened mutations in 14 MODY-related genes and the regulator factor X6 (RFX6) gene in children. Materials and Methods: The presence of clinical features of MODY and negative results for three autoantibody markers of T1DM in children and adolescents were used as inclusion criteria for genetic testing. The screening panel for next-generation sequencing included 14 MODY-related genes (GCK, HNF4A, HNF1A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, KCNJ11, and APPL1) and the RFX6 gene. Results: Twenty-four different variants in MODY-related genes were identified in 49 children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). A 12 variants were classified as P/LP while 12 were interpreted as variant of unknown significance (VUS). Nine of the pathogenic or likely pathogenic variants were found in GCK, two in HNF1B, and one in ABCC8. Three variants were novel, and one was a de novo variant. All of the variants, except one, showed heterozygotic inheritance. Conclusion: This study screened mutations in the 14 MODY-related genes and the regulatory factor X6 (RFX6) gene in Turkish children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). The frequencies of the MODY subtypes differed from previous reports. Although GCK-MODY was the most frequent mutation in Turkish children, similar to previous studies, the second most prevalent MODY subtype was HNF1B-MODY. This study also established three additional novel mutations in different MODY genes.
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Objective: Type 1 diabetes (T1D), one of the most common childhood diseases worldwide, can cause hearing loss through systemic effects. Diabetes-induced hearing loss is considered a progressive sensorineural hearing loss with a gradual onset, typically occurring at high frequencies (HFs). Extended HF (EHF) hearing sensitivity in children with T1D who did not complain of hearing loss was investigated as an early marker for hearing loss at the standard/conventional frequency range of hearing. Methods: Forty-two children (21 with T1D and 21 healthy controls) were evaluated in a case-control design. Conventional and EHF (14,000, 16,000, and 18,000 Hz) audiometry were performed. The diabetes group underwent routine blood biochemistry and glycated hemoglobin A1c measurements. The data were analyzed by the Student's t-test, Mann-Whitney U test, chi-square test, and logistic regression analysis. Results: The mean hearing thresholds were significantly higher (p<0.05) in the diabetes group than in controls at 500, 2,000, 4,000, and 8,000 Hz [all <15 decibel hearing level (dB HL)]. The number of ears with thresholds >15 dB HL at 14,000-18,000 Hz but ≤15 dB HL at 500-4,000 Hz was significantly higher in the diabetes group than in the control group (p=0.049). Conclusion: Children with diabetes showed normal hearing thresholds within the conventional audiometric frequency range but they had higher hearing thresholds during EHF audiometry when compared with controls. Audiometry in these children should be performed using frequencies above 8,000 Hz combined with the conventional frequency range. EHF audiometry may be an effective method for identifying subclinical hearing loss in children with diabetes. Thus, diabetic children with an EHF mean hearing threshold above 15 dB HL should be monitored more closely in terms of blood glucose regulation to prevent diabetes-related hearing loss at the conventional frequency range.
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Diabetes Mellitus Tipo 1 , Pérdida Auditiva , Humanos , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Umbral Auditivo/fisiología , Audición/fisiología , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/etiología , Audiometría/métodosRESUMEN
Objective: Advances in knowledge of neurotrophic factors are now revealing the complex control of energy homeostasis and appetite, as well as the crucial role these factors play in nervous system function. The aim of this study was to assess serum levels of neudesin in adolescents with obesity and to examine the relationship between these levels and metabolic outcomes. Methods: Adolescents, aged 10-17 years were enrolled. Subjects were divided into normal weight, obese and morbidly obese subgroups. Serum neudesin concentrations were compared between the groups. Results: In total, 88 adolescents were recruited, of whom 30 (34.1%) were normal weight, 15 (17.0%) were obese and 43 (48.9%) were morbidly obese. Neudesin levels were significantly lower in obese adolescents than in the control group (p=0.013). A correlation analysis applied to the whole study group revealed a negative correlation between serum neudesin concentration and body mass index (BMI) z scores (r=-0.40, p<0.001). Serum neudesin levels tended to increase in adolescents with metabolic syndrome, insulin resistance, dyslipidaemia, and hypertension but the differences were not significant (p=0.259, p=0.246, p=0.259, and p=0.523, respectively). Conclusion: Serum neudesin levels were significantly correlated with BMI z score in obese adolescents. Generally, serum neudesin levels were low in obese and morbidly obese adolescents and tended to increase with the appearance of metabolic disorders. Both obesity and associated metabolic disorders have multifactorial causes. Therefore, we suggest that the role of the neudesin molecule in the regulatory mechanisms of obesity and metabolic disorders should be further investigated with well-designed studies enrolling larger groups.
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Resistencia a la Insulina , Síndrome Metabólico , Obesidad Mórbida , Obesidad Infantil , Adolescente , Índice de Masa Corporal , Niño , HumanosRESUMEN
OBJECTIVE: Herein, we measured the concentration of insulinlike growth factor I (IGF-I), IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin in the umbilical cord blood of newborns categorized as "small for gestational age" (SGA), "appropriate for gestational age" (AGA), and "large for gestational age" (LGA). Our aim was to elucidate the link between the levels of these proteins and fetal growth. STUDY DESIGN: A total of 96 term infants were included and categorized into three weight categories. Their venous cord blood samples were collected to measure the levels of IGF-I, IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin. RESULTS: IGF-I, visfatin, and leptin levels showed significant differences among the groups. Pairwise comparisons showed that adiponectin (p = 0.023), resistin (p = 0.025), and ghrelin (p = 0.005) levels were significantly lower in the SGA group than in the LGA group. Correlation analyses showed a strong association of IGF-1, IGF-II, and leptin levels with birth weight (r = 0.644, p < 0.001; r = 0.441, p < 0.001; and r = 0.404, p < 0.001, respectively). CONCLUSION: SGA newborns showed a significantly higher visfatin concentration and lower ghrelin, leptin, resistin, and adiponectin levels than the AGA and LGA newborns did.
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Citocinas/sangre , Sangre Fetal/química , Desarrollo Fetal/fisiología , Recién Nacido Pequeño para la Edad Gestacional/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Nicotinamida Fosforribosiltransferasa/sangre , Adiponectina/sangre , Ghrelina/sangre , Humanos , Recién Nacido/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/análisis , Leptina/sangre , Resistina/sangreRESUMEN
Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results: A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves' disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. Two patients were lost to follow up. Conclusion: This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey.
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Antitiroideos/uso terapéutico , Tiroidectomía/métodos , Tirotoxicosis/terapia , Adolescente , Niño , Preescolar , Terapia Combinada , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.
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Diabetes Mellitus Tipo 1/epidemiología , Sistema de Registros/estadística & datos numéricos , Estaciones del Año , Adolescente , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Geografía , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Turquía/epidemiologíaRESUMEN
OBJECTIVE: The granulocyte colony-stimulating factor (G-CSF) is the most commonly used hematopoietic growth factor recombinant DNA technology. It affects bone metabolism by modulating both osteoclast and osteoblast functions. The aim of the present study was to investigate the effects of short-term use of G-CSF on bone metabolism in children with leukemia and solid tumors. METHODS: Thirty-six patients with a malignancy who received G-CSF therapy according to chemotherapy protocols and another 20 growth factor-free cancer patients who were enrolled as controls were included in the study. The serum osteocalcin and urinary free deoxypyridinoline levels were measured before the start of G-CSF therapy, on day 3 after treatment, and 7 days after G-CSF therapy was discontinued. In the control group, the measurements were made during corticosteroid and methotrexate-free chemotherapy. RESULTS: The mean osteocalcin level (8.6±2.3 ng/mL) from before the onset of treatment decreased significantly (7.7±2.3 ng/mL) on day 3 of G-CSF therapy and significantly increased after 7 days of G-CSF therapy (7.9±2.2 ng/mL) (p<0.001 and p<0.001, respectively), which was still significantly lower than the pre-G-CSF values (p<0.001). The urinary free deoxypyridinoline level significantly increased on day 3 of G-CSF treatment (25.6±6.5 nmol/mmol Cr) and significantly decreased after 7 days of G-CSF therapy (22.6±6.4 nmol/mmol Cr) (p<0.001 and p<0.001, respectively), which was still significantly higher than the values recorded before G-CSF therapy (p<0.001). CONCLUSION: The findings show that the short-term use of G-CSF in children with cancer can affect bone metabolism and can play a role in metabolic changes. Decreased osteoblastic activity and increased osteoclastic activity suggest that osteoporosis may be associated with bone pain in these patients.
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The prothrombotic state in type 1 diabetes mellitus (T1DM) has been reported as a plausible cause of vascular complications. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. This study aimed to assess hypercoagulability in children with T1DM using ROTEM. A total of 43 T1DM children (20 females and 23 males) aged 2-18 years and age- and sex-matched 30 healthy control subjects were enrolled in the study group. ROTEM assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] were used to measure and analyze coagulation time (CT), clot formation time, maximum clot firmness (MCF). Glycated hemoglobin levels (HbA1c), diabetic complications, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and dimerized plasmin fragment D (D-dimer) were determined in the study group. The mean duration of T1DM diagnosis was 3.15 ± 2.49 years, and the mean HbA1c level was 8.94 ± 1.88% (74.29 ± 20.59 mmol/mol). None of the patients had macrovascular complications. Nephropathy was present in five patients. In the T1DM group, EXTEM-CT [80.00 (66.75-108.50)] was significantly lower, and EXTEM-MCF [65.00 (64.00-70.00)] and INTEM-MCF [65.00 (62.00-68.00)] were significantly higher than in the controls (p < 0.001, p = 0.026, and p = 0.004, respectively). However, the duration of T1DM and the degree of metabolic control had no influence on these parameters. Platelet count, PT, aPTT, fibrinogen and D-dimer levels were comparable between the diabetic patients and the control group. There were statistically significant correlations between fibrinogen level and INTEM-MCF and EXTEM-MCF (p < 0.001, p = 0.002 and r = 0.545, r = 0.454, respectively) This study shows that decreased levels of CT and increased levels of MCF suggest hypercoagulability in patients with T1DM. Further studies are needed to confirm our findings on a larger number of diabetic patients.
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OBJECTIVE: Irisin and oxytocin can affect energy homeostasis and it has been suggested that they may play an important role in reducing obesity and diabetes. In this study, we aimed to determine the relationship between metabolic parameters (including irisin and oxytocin levels) and anthropometric parameters in obese children. METHODS: Ninety obese children (mean age, 13.85±1.63 years) and 30 healthy controls (mean age, 14.32±1.58 years) were enrolled in this study. Anthropometric and laboratory parameters (glucose, insulin, lipid, oxytocin, and irisin levels) were analyzed. The serum irisin and oxytocin levels were measured by enzyme-linked immunosorbent assay. Bioelectrical impedance was used to determine body composition. RESULTS: Irisin level was higher in the patients than in the controls (p=0.018), and this higher irisin level was correlated with increased systolic blood pressure, body mass index, waist/hip ratio, fat percentage, fat mass, glucose level, insulin level, and homeostasis model assessment of insulin resistance. Serum oxytocin level was significantly decreased in obese children compared to the controls (p=0.049). Also, among the 60 obese patients, oxytocin level was significantly lower in patients with than in those without metabolic syndrome (8.65±2.69 vs. 10.87±5.93 ng/L, respectively), while irisin levels were comparable (p=0.049 and p=0.104, respectively). There were no statistically significant relationships between oxytocin or irisin levels and lipid levels (p>0.05). CONCLUSION: Obese children had significantly higher irisin levels than the healthy controls. Additionally, this study shows for the first time that oxytocin level is significantly lower in obese compared with non-obese children and also lower in obese children with metabolic syndrome compared to those without.
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Fibronectinas/sangre , Síndrome Metabólico/sangre , Obesidad/sangre , Oxitocina/sangre , Adolescente , Niño , Femenino , Humanos , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/metabolismo , Obesidad/diagnóstico , Obesidad/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Curva ROCRESUMEN
Horner syndrome (HS), caused by an interruption in the oculosympathetic pathway, is characterised by myosis, ipsilateral blepharoptosis, enophthalmos, facial anhydrosis, and vascular dilation of the lateral part of the face. HS is a rare complication of thyroidectomy. A 15-year-old female patient presented with solitary solid and large nodule in the right thyroid lobe. Ultrasound-guided fine-needle aspiration was performed and the cytological examination results were undefined. The patient underwent a total thyroidectomy. On postoperative day 2, she developed right-sided myosis and upper eyelid ptosis. HS was diagnosed. Interestingly, the patient exhibited an incomplete clinical syndrome with the absence of vasomotor symptoms. We herein report a case of HS in a 15-year-old female patient after total thyroidectomy. The possible causes of HS were ischaemia-induced nerve damage and stretching of the cervical sympathetic chain by the retractor during thyroidectomy. Clinicians should be aware of the possibility of this rare but important surgical complication.
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AIMS: To evaluate the management strategies, glycemic control and complications of pediatric type 1 diabetes mellitus (T1DM) patients in Turkey. METHODS: Study included 498 patients with T1DM between the ages 1-18. Data provided from patients' hospital files were recorded on standard case report forms by applicant clinicians within the 3months of data collection period between October 2012 and July 2013. RESULTS: Mean age of patients was 11.3±3.8years. Mean duration of DM was determined as 3.7±3.1years. Majority of patients (85.5%) used basal/bolus injection (BBI), and 6.5% used continuous subcutaneous insulin infusion pump. Assessment of glycemic control based on HbA1c levels showed that 29.1% of patients had an HbA1c value <7.5% (58mmol/mol), 16.1% had a value between 7.5% (58mmol/mol) and 8% (64mmol/mol), 19.1% had a value between 8.1% (64mmol/mol) and 9%(75mmol/mol) and 35.7% a value >9%(75mmol/mol). Hypoglycemia was reported in 145 (29.1%) patients and the number of severe hypoglycemic attacks in the last 3months was 1.0±2.4. Taking into consideration the carbohydrate count and insulin correction dose and parents with high socioeconomic status was related to have better glycemic control. The most common comorbidities were Hashimoto's thyroiditis/hypothyroidism (6.2%) followed by celiac disease (3.8%), epilepsy(1.2%), and asthma(1.0%). CONCLUSIONS: BBI insulin therapy is widely used among pediatric T1DM patients in Turkey. However, despite improvements in treatment facilities and diabetic care, glycemic control is not at a satisfactory level. Therefore, new and comprehensive initiatives require for pediatric T1DM patients with poor glycemic control. Promoting use of carbohydrate count and insulin correction doses may improve the glycemic control of pediatric T1DM in Turkey.
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Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Adolescente , Niño , Preescolar , Estudios Transversales , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Masculino , TurquíaRESUMEN
OBJECTIVE: Type 1 diabetes mellitus (T1DM) may lead to deficiencies in trace elements that have substantial functions in the human organism. Changes in serum magnesium (Mg), copper (Cu), and zinc (Zn) levels are correlated with metabolic control and diabetes complications. The aim of this study was to evaluate the intra-erythrocyte levels of trace elements and urinary Mg excretion following intravenous (iv) Mg tolerance testing in children with T1DM. METHODS: A total of 43 children aged 2-18 years with T1DM and age/gender-matched 25 healthy children were included in the study. The iv Mg tolerance test was performed following the measurement of intra-erythrocyte Mg (eMg1), Cu (eCu1), and Zn (eZn1) levels using the atomic absorption spectrophotometer method. The Mg retention ratio was estimated from measurements in 24 h urine samples. RESULTS: No statistically significant difference was found for eMg1, eCu1, and eZn1 levels between the patient and control groups (p>0.05). In the patient group, the eMg1, eCu1, and eZn1 levels measured after the iv Mg tolerance test significantly increased compared with the baseline levels (p<0.05), and the Mg excretion ratio measured from the urine collected after the iv MgSO4 infusion was >50%. CONCLUSION: The increased retention value following the iv Mg tolerance testing indicates intracellular Mg deficiency in children with T1DM.
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Cobre/sangre , Diabetes Mellitus Tipo 1/sangre , Eritrocitos/química , Magnesio/sangre , Zinc/sangre , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Espectrofotometría Atómica , Oligoelementos/análisisRESUMEN
Ovotesticular disorder of sexual development (DSD), formerly known as true hermaphroditism, is a rare form of DSD in which both testicular and ovarian tissues are present in the same individual either in a single gonad (ovotestis) or in opposite gonads with a testis and an ovary on each side. The diagnosis of ovotesticular DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous. Herein, we report two patients with ovotesticular DSD-one presenting with ambiguous genitalia on the third day after birth and the other with short stature and primary amenorrhea in adolescence. Clinical and histopathological investigation revealed a sex-determining region on the Y chromosome (SRY)-positive 46,XX karyotype and bilateral ovotestes in case 1 and a 46,XY karyotype with hypergonadotropic hypogonadism and a streak gonad in one ovotestis with dysgerminoma, gonadoblastoma, and papillary tubal hyperplasia in the contralateral ovotestis in case 2. Laparoscopic examination and gonadal biopsy for histopathological diagnosis remain the cornerstones for a diagnosis of ovotesticular DSD. Moreover, SRY positivity in a 46,XX patient, a 46,XY karyotype, an intra-abdominal gonad, and the age of patient at the time of diagnosis are predictive risk factors for the development of gonadoblastoma and/or dysgerminoma in ovotesticular DSD.
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Trastornos del Desarrollo Sexual/diagnóstico , Trompas Uterinas/patología , Gonadoblastoma/diagnóstico , Neoplasias Ováricas/diagnóstico , Trastornos Ovotesticulares del Desarrollo Sexual/diagnóstico , Adolescente , Trastornos del Desarrollo Sexual/complicaciones , Trastornos del Desarrollo Sexual/genética , Femenino , Gonadoblastoma/complicaciones , Humanos , Hiperplasia , Recién Nacido , Cariotipo , Masculino , Neoplasias Ováricas/complicaciones , Trastornos Ovotesticulares del Desarrollo Sexual/complicaciones , Trastornos Ovotesticulares del Desarrollo Sexual/genéticaRESUMEN
AIM: Our aim was to describe the clinical and genetic findings in an adolescent male with isolated follicle-stimulating hormone (FSH) deficiency and demonstrate the efficacy of recombinant human FSH (rhFSH) replacement in this case. METHODS: A 14.5-year-old adolescent male was referred with normal pubertal development and small testes. Serum testosterone, FSH, and luteinising hormone (LH) were measured at baseline and after gonadotropin-releasing hormone (GnRH) stimulation. Testicular biopsy was performed, and rhFSH replacement was administered for 6 months. The patient's FSHß gene was amplified and sequenced. RESULTS: Basal and GnRH-stimulated FSH levels were undetectable, in contrast with increased LH levels under both conditions. Histopathological investigation of a testicular biopsy specimen revealed a reduced number of Sertoli cells, the absence of germ cells, Leydig cell hyperplasia, and a thickened basement membrane in seminiferous tubules. The testicular size changed from 1 ml at baseline to 6 ml after 6 months of rhFSH replacement. Sequencing of the FSHß gene exon 3 revealed a new missense mutation (c.364T>C, resulting in p.Cys122Arg) in a homozygous state in the patient; both parents and a sister carried the same mutation in a heterozygous state. We also compared our case with all similar cases published previously. CONCLUSION: We herein described an adolescent male with isolated FSH deficiency due to a novel FSHß gene mutation associated with a prepubertal testes size and normal virilisation.
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Hormona Folículo Estimulante , Terapia de Reemplazo de Hormonas , Mutación Missense , Adolescente , Sustitución de Aminoácidos , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/deficiencia , Hormona Folículo Estimulante/genética , Hormona Folículo Estimulante/uso terapéutico , Humanos , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Hormona Luteinizante/sangre , Masculino , Proteínas Recombinantes/uso terapéutico , Células de Sertoli/metabolismo , Células de Sertoli/patología , Testosterona/sangreRESUMEN
OBJECTIVE: Growth hormone-deficient (GHD) children have been found to have higher cardiovascular mortality rates and an increased carotid intima-media thickness (CIMT). This study investigated the risk of atherosclerosis and the effect of recombinant growth hormone (rhGH) replacement therapy on the lipid profile and CIMT in GHD children. DESIGN: A total of 40 GHD children (mean age: 12.3±2.04 years) were investigated before and after 1 year of rhGH therapy at a dosage of 0.03 mg/kg/day and 40 age- and sex-matched healthy children (mean age: 12.1±2.23 years) were enrolled as a control group, in the same pubertal stage. Fasting blood samples were obtained for lipid profile, IGF-1, and IGFBP-3 analyses. The patients and controls underwent CIMT measurements before and after 1 year of rhGH treatment. RESULTS: The growth velocity and height standard deviation scores increased significantly over 1 year of treatment in all patients. The total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and atherogenic index (Ai) values were increased while the high-density lipoprotein (HDL) cholesterol value was decreased in the GHD children, as compared to the controls; however, the triglyceride (TG) level was comparable. After 1 year of treatment, a significant decrease in the TC, LDL cholesterol, and Ai values as well as a significant increase in the HDL value were observed in the GHD patients, with the values becoming similar to those in the control group. The mean CIMT was significantly greater in the GHD subjects than in the controls. After 1 year of therapy, the CIMT in the GHD subjects had decreased significantly; however, it was still greater than that in the control group. IGF-1 was negatively correlated with TC, LDL cholesterol, Ai, right CIMT, and left CIMT. CONCLUSIONS: GHD is associated with increased atherosclerotic risk in children. An improved lipid profile and CIMT were detected after 1 year of hormone replacement therapy.
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Aterosclerosis/epidemiología , Enanismo Hipofisario/epidemiología , Dislipidemias/epidemiología , Terapia de Reemplazo de Hormonas , Adolescente , Aterosclerosis/sangre , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/etiología , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Niño , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Enanismo Hipofisario/sangre , Enanismo Hipofisario/tratamiento farmacológico , Dislipidemias/sangre , Femenino , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Triglicéridos/sangreRESUMEN
The aim of this study was to determine reliable cut-off levels of basal gonadotropin and to assess the correlation of obstetric ultrasound parameters with the GnRH stimulation test. The GnRH stimulation test was performed in a cohort of young female patients who presented at our hospital for the evaluation of early signs of puberty. Using receiver operating curves (ROCs), the sensitivity and specificity of basal luteinising hormone (LH), follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, oestradiol levels and ultrasonographic parameters were evaluated at each level, and the area under curve (AUC) was measured. One hundred female children were assessed. We found that LH levels, peak LH/FSH ratio, fundal/cervical ratio, uterus length, and ovarian volume were reliable predictors of central precocious puberty (CPP). Cut-off levels of basal LH and the peak LH/FSH ratio had high specificity in our cohort. In addition, obstetric ultrasound parameters represent reliable predictors for the diagnosis of CPP.
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Técnicas de Diagnóstico Endocrino , Hormona Liberadora de Gonadotropina , Ovario/diagnóstico por imagen , Pubertad Precoz/diagnóstico , Útero/diagnóstico por imagen , Niño , Femenino , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Hormona Luteinizante/sangre , Pronóstico , Pubertad Precoz/sangre , Curva ROC , Maduración Sexual , UltrasonografíaRESUMEN
Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum of CYP21A2 mutations in NCAH patients. Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL. Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous. Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent.
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Congenital hyperinsulinism (CHI) is a common cause of hypoglycemia in infants. We report three cases of CHI with differing clinical, biochemical, and molecular genetic spectra. One patient was unresponsive to medical treatment and died after subtotal pancreatectomy because of complications due to the surgery. Two patients have been followed successfully with medical treatment. Early diagnosis and appropriate treatment of CHI are essential to prevent morbidity and mortality.
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Glucemia/metabolismo , Hiperinsulinismo Congénito/genética , Células Secretoras de Insulina/metabolismo , Insulina/sangre , Hiperinsulinismo Congénito/metabolismo , Hiperinsulinismo Congénito/cirugía , ADN/genética , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos , Humanos , Recién Nacido , Masculino , Mutación , Pancreatectomía , Canales de Potasio de Rectificación Interna/genética , Canales de Potasio de Rectificación Interna/metabolismo , Receptores de Sulfonilureas/genética , Receptores de Sulfonilureas/metabolismoRESUMEN
Deletions and mutations in the 5-alpha-reductase type 2 (SRD5A2) gene have been identified in 46,XY disorders of sexual differentiation (DSD). The clinical spectrum is heterogeneous, varying from a normal female external genital appearance to clitoromegaly and isolated micropenis or microphallus associated with hypospadias of various degrees. We describe a 46,XY DSD patient with a homozygous c.307C>T (p.R103X) mutation in the SRD5A2 gene. The case presented with a normal female external genital phenotype.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Disgenesia Gonadal 46 XY/genética , Disgenesia Gonadal 46 XY/patología , Proteínas de la Membrana/genética , Mutación Missense/genética , Femenino , Genitales Femeninos/patología , Genitales Masculinos/patología , Homocigoto , Humanos , Lactante , Masculino , FenotipoRESUMEN
Hyponatremia develops as a result of the inappropriate secretion of antidiuretic hormone. In rare cases, it develops as an iatrogenic complication. For example, acute iatrogenic post-tonsillectomy hyponatremia has been described in children following the infusion of hypo- or isotonic fluid. We report a case of rapidly developing post-tonsillectomy iatrogenic hyponatremia in a 5-year-old girl following an excessive infusion of hypotonic fluid. Her signs and symptoms began with nausea and vomiting and progressed to seizures and coma. We corrected the electrolyte disturbance by infusing a 3% sodium chloride solution until her neurologic manifestations disappeared, at which time her serum sodium concentration had risen back to 135 mEq/L. Otolaryngologists are not generally exposed to much information about hyponatremia, so we must be aware of its associated neurologic signs and symptoms.