39 results on '"Yıldırım, Ruken"'
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2. The clinical and laboratory features of patients with triple A syndrome: a single-center experience in Turkey
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Yıldırım, Ruken, Unal, Edip, Tekmenuray-Unal, Aysel, Taş, Funda Feryal, Özalkak, Şervan, Çayır, Atilla, and Özbek, Mehmet Nuri
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- 2023
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Catalog
3. Cytochrome P450 oxidoreductase deficiency caused by a novel mutation in the POR gene in two siblings: case report and literature review
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Unal, Edip, Demiral, Meliha, Yıldırım, Ruken, Taş, Funda Feryal, Ceylaner, Serdar, and Özbek, Mehmet Nuri
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- 2021
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4. Evaluation of cardiac electrophysiological features in patients with premature adrenarche.
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Ertaş, Kerem, Gül, Özlem, Yıldırım, Ruken, and Özalkak, Şervan
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This study aimed to analyze the cardiac effects of hyperandrogenism in premature adrenarche (PA) and evaluate the risk of arrhythmia development. Fifty patients with PA and 50 healthy children from a pediatric endocrinology outpatient clinic were included in the study. The patients underwent echocardiography and electrocardiographic evaluations. Conventional echocardiography, tissue Doppler echocardiography, repolarization time, and repolarization dispersion time were evaluated. The median age in the PA and control groups was 7.91 years (5.83–9.25), 8.08 years (5.75–9.33), respectively. Thirty percent of patients in the PA group were male. While mitral early diastolic velocity deceleration time (DT), isovolumetric relaxation time (IRT), and E/e' ratio were significantly higher in the PA group than in the control group, mitral lateral annulus tissue Doppler early diastolic velocity was significantly lower (p=0.0001, 0.0001, 0.003, 0.0001). While P wave dispersion (PWD), Tpe, and QT-dispersion (QT-d) values were significantly higher in the PA group than in the control group, the P minimum value was significantly lower in the PA group (p=0.0001, 0.02, 0.004, and 0.0001, respectively). Early subclinical diastolic dysfunction was observed in the PA group. There was an increased risk of atrial arrhythmia with PWD and an increased risk of ventricular arrhythmia with increased Tpe and QT-d. There was a correlation between testosterone levels and diastolic function parameters. The increased risk of atrial arrhythmia is closely related to diastolic function. [ABSTRACT FROM AUTHOR] more...
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- 2024
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5. Clinical Variability in a Family with Noonan Syndrome with a Homozygous PTPN11 Gene Variant in Two Individuals.
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Yıldırım, Ruken, Ünal, Edip, Özalkak, Şervan, Akalın, Akçahan, Aykut, Ayça, and Yılmaz, Nevzat
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NOONAN syndrome , *CONSANGUINITY , *DESCRIPTIVE statistics , *GENES , *GENETIC mutation , *MOLECULAR biology , *DATA analysis software - Abstract
Objective: Noonan syndrome (NS) is characterized by dysmorphic facial features, short stature, congenital heart defects, and varying levels of developmental delays. It is a genetic, multisystem disorder with autosomal dominant inheritance and is the most common of the RASopathies. In approximately 50% of patients, NS is caused by variants in the Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11) gene. The aim of this study was to evaluate two patients with a previously reported PTPN11 homozygous variant for the first time and seven other kindred members carrying the same heterozygous variant in terms of clinical, biochemical, genetic, and response to treatment. Methods: Nine patients diagnosed with NS due to the same variants in the PTPN11 gene were included in the study. Results: The median (range) age at diagnosis was 11.5 (6.8-13.9) years and the mean follow-up duration was 4.7 (1-7.6) years. In eight patients (88.9%), short stature was present. The height standard deviation score of the patients on admission was -3.24±1.15. In six of the patients, growth hormone treatment was initiated. Cardiovascular or bleeding disorders were not detected in any of the patients. Three (33.3%) had hearing loss, two (22.2%) had ocular findings and one (11.1%) had a horseshoe kidney. The mean psychomotor development performance score was 84.03±17.09 and the verbal score was 82.88±9.42. Genetic analysis revealed a variant in the PTPN11 gene [c.772G>A; (p.Glu258Lys)] that had been previously described and was detected in all patients. Two patients were homozygous for this variant and short stature was more severe in these two. Conclusion: A previously described in PTPN11 affected nine members of the same kindred, two with homozygous inheritance and the remainder being heterozygous. To the best of our knowledge, these are the first homozygous PTPN11 case reports published, coming from two related consanguineous families. [ABSTRACT FROM AUTHOR] more...
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- 2024
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6. Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.
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Tarçın, Gürkan, Çatlı, Gönül, Çetinkaya, Semra, Eren, Erdal, Kardelen, Aslı Derya, Akıncı, Ayşehan, Böber, Ece, Kara, Cengiz, Yıldırım, Ruken, Er, Eren, Polat, Recep, Özhan, Bayram, Yıldız, Melek, Kor, Yılmaz, Evliyaoğlu, Olcay, Dündar, Bumin, and Ercan, Oya more...
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CUSHING'S syndrome ,JUVENILE diseases ,TREATMENT effectiveness ,MAGNETIC resonance imaging ,ADRENOCORTICOTROPIC hormone ,ADRENAL insufficiency - Abstract
Objective: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. Design: National, multicenter and retrospective study. Patients: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow‐up data of the children with CD between December 2015 and March 2017. Measurements: Diagnostic tests of CD and tumour size. Results: Thirty‐four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late‐night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow‐up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. Conclusions: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one‐third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow‐up after surgery. [ABSTRACT FROM AUTHOR] more...
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- 2024
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7. A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation
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Unal, Edip, Yıldırım, Ruken, Taş, Funda Feryal, Tekin, Suat, Sen, Askin, and Haspolat, Yusuf Kenan
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- 2018
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8. Santral Puberte Prekokslu Her Olguya Kraniyal Manyetik Rezonans Görüntüleme Gerekli Mi?
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Yıldırım, Ruken, Unal, Edip, and Ayaz, Ercan
- Abstract
Copyright of Van Tip Dergisi is the property of Yuzuncu Yil University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2023
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9. Disparities in Responsibility Sharing and Gender Differences in Diabetes Care: Changes in Occupational Life of Parents of Children with Type 1 Diabetes.
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Karakus, Kagan E., Sakarya, Sibel, Saßmann, Heike, Yıldırım, Ruken, Özalkak, Şervan, Özbek, Mehmet N., Yıldırım, Nurdan, Delibağ, Gülcan, Eklioğlu, Beray S., Haliloğlu, Belma, Aydın, Murat, Kırmızıbekmez, Heves, Gökçe, Tuğba, Can, Ecem, Eviz, Elif, Yesiltepe-Mutlu, Gul, and Hatun, Şükrü more...
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RESEARCH ,CHILD care ,UNEMPLOYMENT ,CONFIDENCE intervals ,CROSS-sectional method ,TYPE 1 diabetes ,RESPONSIBILITY ,SEX distribution ,EMPLOYMENT ,CHILDREN'S health ,QUESTIONNAIRES ,DESCRIPTIVE statistics ,ODDS ratio - Abstract
Aims. To evaluate responsibility sharing between parents of children with type 1 diabetes and change in their occupational status one year after the diagnosis. Methods. In this cross-sectional multicenter study, parents of children under the age of 18 with a diagnosis of type 1 diabetes answered a questionnaire assessing diabetes-related responsibility sharing between parents, and occupational changes due to child's diabetes. Changes in the occupational status with associated factors and distribution of diabetes-related responsibilities between parents were analyzed. Results. Among parents of 882 children (mean (SD) age at diagnosis was 7 (3.8) years, female 52.5%), unemployment increased significantly in mothers (59.0% vs. 67.1%; p < 0.001), but not in fathers (10.4% vs. 10.7%; p > 0.05) within 1 year after their child's diagnosis. Working mother's occupational withdrawal was associated with the child's age at diagnosis (OR = 0.92, [95% CI 0.86–0.99]; p = 0.02) and mother's education (compared to a university degree or above, high school graduate (OR = 2.93, [95% CI 1.59–5.4]; p < 0.001) and not graduated high school (OR = 8.4, [95% CI 3.56–19.83]; p < 0.001)). According to the mothers, none of the responsibilities in diabetes care were shared equally between parents, while fathers reported most responsibilities were shared equally. Compared to mothers who preserved their occupation after the diagnosis, mothers who quit their occupation had significantly higher responsibility scores (2.04 vs. 1.55; p = 0.04), especially in diabetes care at school (p < 0.01). Conclusions. The difference in parents' perceptions of their involvement in their child's diabetes is remarkable. Gender differences in the child's diabetes care extend to the occupational life of parents unequally. [ABSTRACT FROM AUTHOR] more...
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- 2023
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10. Isolated hypogonadotropic hypogonadism in adolescence: Do we need to measure the pituitary, stalk or other imaging markers? A retrospective magnetic resonance imaging study.
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Ayaz, Ercan, Yıldırım, Ruken, Çelebi, Canan, and Özalkak, Şervan
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Background. Rapid changes in the size of the pituitary gland occur during the pubertal period. Therefore, measuring and reporting magnetic resonance imaging (MRI) in adolescents with pituitary disorders can cause unease among radiologists. Our aim was to compare the size of the pituitary gland, stalk and other previously described imaging tools in patients with isolated hypogonadotropic hypogonadism (HH) versus adolescents with a normal pituitary gland. Methods. Forty-one patients (22 female, 19 male, mean age 16.3 ±2.0 years) with HH who underwent MRI prior to starting hormone treatment were enrolled. Age, sex, and genetic mutations were noted. Pituitary height, width on the coronal plane, anteroposterior (AP) diameter on the sagittal plane, stalk thickness, pons ratio (PR), clivus canal angle (CCA) and Klaus index (KI) were measured by two radiologists twice with a one-month interval blinded to each other and patient information. Measurements were compared with the control group, including 83 subjects with normal hypothalamic-pituitary-gonadal axis and normal pituitary gland on MRI. Inter-rater and intra-rater agreements were also evaluated. Results. No significant differences were found between the two groups regarding height, width or AP diameter (p = 0.437, 0.836, 0.681 respectively). No significant differences were found between the two groups regarding CCA and PR (p = 0.890, 0.412 respectively). The KI of the male patients was significantly higher than that of the female patients and the control group (p < 0.001). The interrater agreement was moderate for pituitary height and width, poor for pituitary AP diameter and stalk thickness, good for PR and KI, and excellent for CCA. Conclusions. The measurements of the pituitary gland, stalk and posterior fossa structures were similar in adolescents with or without isolated HH. Consequently, pituitary gland, stalk or other posterior fossa measurements are unnecessary when evaluating a normal appearing pituitary gland on MRI. [ABSTRACT FROM AUTHOR] more...
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- 2023
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11. Hereditary Spherocytosis: Evaluation of 68 Children
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Konca, Çapan, Söker, Murat, Taş, Mehmet Ali, and Yıldırım, Ruken
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- 2015
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12. Noonan syndrome: Neuroimaging findings and morphometric analysis of the cranium base and posterior fossa in children.
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Ayaz, Ercan, Yıldırım, Ruken, Çelebi, Canan, and Ozalkak, Servan
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NOONAN syndrome , *POSTERIOR cranial fossa , *SKULL , *CRANIOMETRY , *SKULL base , *CORPUS callosum , *CHILD patients - Abstract
Background and Purpose: There are a few studies regarding intracranial findings in neonates with Noonan syndrome (NS); however, there are no quantitative analyses in a pediatric population. The aim of this study was to find characteristic intracranial abnormalities and to quantitatively analyze the posterior fossa and cranium base in children with NS. Methods: A total of 30 patients (11 females and 19 males, mean age 13.1 ± 4.3 years) were retrospectively identified between July 2017 and June 2022. Twenty‐one patients had MRI. Age at MRI examination, sex, genetic mutations, and clinical findings were noted. In patients with MRI, the presence of white matter lesions, basal ganglia lesions, corpus callosum abnormalities, sellar/parasellar lesions, and tonsillar ectopia was noted. For morphometric analysis, cerebellar diameter, vermis and clivus heights, cranial base, tentorial and infratentorial angles, and McRae's and Twining's lines were each measured twice by two radiologists individually. Results: The most common lesions were focal white matter lesions, followed by abnormalities of the splenium of the corpus callosum. The cerebellar diameter, vermis and clivus heights, Twining's line, and infratentorial angle were significantly smaller; cranial base angle and tentorial angle were significantly larger in NS (p <.05). Interrater and intrarater agreements were the highest for cerebellar diameter and the lowest for tentorial angle measurements. Conclusion: Children with NS had characteristic callosal and tentorial findings and neuroimaging findings similar to other RASopathies. This study also shows that a small posterior fossa and flattening of the cranial base are present in children with NS, which may aid in diagnosis. [ABSTRACT FROM AUTHOR] more...
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- 2023
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13. Evaluation of Clinical Characteristics of Vitamin D Dependent Rickets Type 1 (VDDR-1) Patients and Importance of Early Diagnosis.
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Yıldırım, Ruken, Ünal, Edip, and Tekmenüray, Aysel
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GENETICS , *SEQUENCE analysis , *RICKETS , *RETROSPECTIVE studies , *ACQUISITION of data , *MEDICAL records , *DESCRIPTIVE statistics , *HYPOCALCEMIA , *HYPOPHOSPHATEMIA , *VITAMIN D deficiency , *DATA analysis software , *SEIZURES (Medicine) , *GROWTH disorders , *SYMPTOMS - Abstract
Introduction: Vitamin D-dependent rickets type 1 (VDDR-1) is an autosomal recessive disorder caused by 1-α-hydroxylase enzyme deficiency. This rare disease occurs due to biallelic pathogenic variants in the CYP27B1 gene. We evaluated VDDR-1 patients retrospectively in terms of clinical and biochemical characteristics, treatment response, and genetic results. Materials and Methods: VDDR-1 cases with biallelic variants in CYP27B1 from 12 families were included. Demographic and clinical data were extracted from records. Following DNA isolation and standardized PCR, we performed next- generation sequencing with Miseq device. Data analysis was performed using IGV 2.3 software. Results: The cohort included 22 patients, 11 (50%) female and 11 male. Median age at diagnosis was 12 (7.75-18) months. Mean calcium, phosphorus, alkaline phosphatase (ALP) and vitamin D concentration was 7.6±0.98 mg/dL, 2.9±0.77 mg/dL, 1149±692 IU/L, 391±181 pg/mL, and 55±38 ng/mL, respectively at diagnosis The most common reasons for presentation were growth retardation, short stature, convulsions, and extremity deformity. The most common variant was the previously identified c.195 + 2T>G substitution, which was detected in 5 families. The second most common variant was another previously reported c.574A>G (p.Lys192Glu) variant, which was detected in 3 families. c.171delC (p.Leu.58Cfs*20), c.240delT (p.Phe80Leufs*79), and c.1166G>A(p.Arg389His) homozygous variants and c.1215_1215+2delinsCGA/c.1474C>T (p.Arg492Trp) compound heterozygous variant were detected in one family each. Conclusion: VDDR-1 should be considered in rickets patients not recovering with high-dose vitamin D therapy. Delayed diagnosis of VDDR-1 may lead to unnecessary orthopedic surgery in some cases. We are of the opinion that providing early diagnosis, treatment and genetic counseling will give reliable and important information to families. [ABSTRACT FROM AUTHOR] more...
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- 2022
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14. Final Height in GnRH Analogue Treatment in Girls Diagnosed with Early Puberty: Comparison with Untreated Controls.
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Karakaya, Amine Aktar, Ünal, Edip, Beştaş, Aslı, and Yıldırım, Ruken
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PRECOCIOUS puberty ,STATURE ,RETROSPECTIVE studies ,PATIENTS ,GONADOTROPIN releasing hormone ,TREATMENT effectiveness ,HOSPITAL admission & discharge ,DESCRIPTIVE statistics ,BODY mass index ,WOMEN'S health ,EVALUATION ,CHILDREN ,ADULTS - Abstract
Copyright of Journal of Current Pediatrics / Guncel Pediatri is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2022
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15. Yenidoğan Sepsisi Tanısı ve Prognozunda IL-6, IL-8, TNF-α ve C-Reaktif Protein Düzeyleri.
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Yıldırım, Ruken and Devecioğlu, Mehmet Celal
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Copyright of Van Tip Dergisi is the property of Yuzuncu Yil University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2022
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16. Revisiting the Annual Incidence of Type 1 Diabetes Mellitus in Children from the Southeastern Anatolian Region of Turkey: A Regional Report.
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Özalkak, Şervan, Yıldırım, Ruken, Tunç, Selma, Ünal, Edip, Taş, Funda Feryal, Demirbilek, Hüseyin, and Özbek, Mehmet Nuri
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TYPE 1 diabetes , *DISEASE incidence , *DESCRIPTIVE statistics , *DIABETIC acidosis - Abstract
Objective: The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending on region and ethnicity. Our group first reported T1D incidence in Diyarbakır in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report. Methods: Hospital records of patients diagnosed with T1D in Diyarbakır city between 1st January 2020 and 31st December 2020 and aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI). Results: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18 years age group. Thus the T1D incidence was 8.03/105 in the 0-18 age group and was higher in the 0-14 age group at 9.14/105. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with diabetic ketoacidosis was 64.9%. Conclusion: The annual incidence of pediatric T1D in Diyarbakır city increased from 7.2/105 to 9.14/105 within the last decade. The rate of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one. [ABSTRACT FROM AUTHOR] more...
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- 2022
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17. Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variation.
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Demir, Selma, Yaşar Köstek, Hümeyra, Sanrı, Aslıhan, Yıldırım, Ruken, Özgüç Çömlek, Fatma, Yalçıntepe, Sinem, Deveci, Murat, Atlı, Emine İkbal, Atlı, Engin, Eker, Damla, Gürkan, Hakan, and Tütüncüler Kökenli, Filiz more...
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- 2022
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18. Targeted High-Throughput Sequencing Analysis Results of Osteogenesis Imperfecta Patients from Different Regions of Turkey.
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Demir, Selma, Yalçıntepe, Sinem, Atlı, Emine İkbal, Sanrı, Aslıhan, Yıldırım, Ruken, Tütüncüler, Filiz, Çelik, Mehmet, Atlı, Engin, Özemri Sağ, Şebnem, Eker, Damla, Temel, Şehime, and Gürkan, Hakan
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- 2021
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19. Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations.
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Demirbilek, Huseyin, Cayir, Atilla, Flanagan, Sarah E., Yıldırım, Ruken, Kor, Yılmaz, Gurbuz, Fatih, Haliloğlu, Belma, Yıldız, Melek, Baran, Rıza Taner, Akbas, Emine Demet, Demiral, Meliha, Ünal, Edip, Arslan, Gulcin, Vuralli, Dogus, Buyukyilmaz, Gonul, Al-Khawaga, Sara, Saeed, Amira, Maadheed, Maryam Al, Khalifa, Amel, and Onal, Hasan more...
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PEOPLE with diabetes ,PITUITARY dwarfism ,FERRITIN ,GENE enhancers ,FETAL growth retardation ,PANCREAS ,RESEARCH ,GENETICS ,CHOLESTASIS ,GENETIC mutation ,NEONATAL diseases ,RESEARCH methodology ,DIABETES ,EXOCRINE pancreatic insufficiency ,MEDICAL cooperation ,EVALUATION research ,SELF-report inventories ,COMPARATIVE studies ,SYMPTOMS ,RESEARCH funding ,TRANSCRIPTION factors ,GENETIC techniques ,LONGITUDINAL method ,DISEASE complications - Abstract
Context: Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterized.Objective: To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations.Setting: Twelve tertiary pediatric endocrine referral centers.Patients: Thirty patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years.Main Outcome Measures: Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated hemoglobin) characteristics, pancreas imaging, and genetic analysis.Results: Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n = 18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS = -3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis: 5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long-term follow-up. Previously undescribed common features in our cohort were transiently elevated ferritin level (n = 12/12 tested), anemia (19/25), and cholestasis (14/24). Postnatal growth was impaired (median height SDS: -2.35, median BMI SDS: -0.52 SDS) with 20/29 (69%) cases having growth retardation.Conclusion: We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extrapancreatic features which likely reflect long-term intestinal malabsorption. [ABSTRACT FROM AUTHOR] more...- Published
- 2020
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20. A rare cause of delayed puberty in two cases with 46,XX and 46,XY karyotype: 17 α-hydroxylase deficiency due to a novel variant in CYP17A1 gene.
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Unal, Edip, Yıldırım, Ruken, Taş, Funda Feryal, Tekin, Suat, Ceylaner, Serdar, and Haspolat, Yusuf Kenan
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HYPOKALEMIA , *GENETIC mutation , *SEX differentiation disorders , *ADRENOGENITAL syndrome , *PUBERTY , *ENZYME deficiency - Abstract
Aims: 17α-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia (CAH) which is inherited autosomal recessive. It occurs result of a mutations in gene cytochrome (CYP)17A1, which encodes both 17α-hydroxylase and 17,20-lyase enzymes. The main clinical findings of the disease are delayed puberty, primary amenorrhea in females, and disorders of sex development (DSD) in males. Also, hypertension and hypokalemia can be seen in both sexes. In this paper, we describe the clinical and genetic changes of two patients with 46,XY and 46,XX karyotypes from two different families who were diagnosed with complete 17α-hydroxylase enzyme deficiency. Methods: In this study various methods including clinical, hormonal, radiological and genetic analyzes were used. Blood samples were obtained for genetic tests. Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of the CYP17 gene were assessed by polymerase chain reaction and direct sequencing analysis. Results: 17α-hydroxylase deficiency was diagnosed in 2 patients with 46,XX and 46,XY karyotype who presented with hypertension and delayed puberty. The pQ80 * (c.238C > T) mutation detected in both cases was evaluated as a novel variant. [ABSTRACT FROM AUTHOR] more...
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- 2020
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21. Jinekomasti İle Tanı Alan 46,Xx Testiküler Cinsel Gelişim Bozukluğu Olgusu.
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Yıldırım, Ruken, Unal, Edip, and Haspolat, Yusuf Kenan
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46, XX testicular disorder is a rare disorder characterized by karyotype analysis being 46,XX in an individual whose phenotype is male. Gynecomastia after puberty, small testes and sterility due to azoospermia may occur, but penile length and pubic hair are usually normal. In rare cases, inadequate virilization of the external genitalia; hypospadias, undescended testis, or ambigius genitalia could be seen. Short stature and normal mental development are other clinical features of 46, XX testicular disorder. A 13 1/2 old male patient presented to our outpatient clinic with the complaint of gynaecomastia. İn the physical examination revealed that short stature (10th percentile), gynecomastia and small testes. On laboratory examination, LH: 24.32 mIU / ml, FSH: 34.26 mIU / ml, Estradiol: 34.53 pg / ml, Total Testosterone: 1.62 ng / ml, after this results karyotype analysis was performed and reported as 46 XX. With positive SRY gene analysis, the patient was diagnosed with 46, XX testicular sexual development disorder. This case is presented to emphasize the importance of chromosome analysis when hypergonadotropic hipogonadism is detected in patients presenting with gynecomastia during puberty. [ABSTRACT FROM AUTHOR] more...
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- 2019
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22. A Novel Mutation of AMHR2 in Two Siblings with Persistent Müllerian Duct Syndrome.
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Unal, Edip, Yıldırım, Ruken, Tekin, Suat, Demir, Vasfiye, Onay, Hüseyin, and Haspolat, Yusuf Kenan
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TESTICULAR diseases , *DISEASES in men , *INGUINAL hernia , *SEX differentiation disorders , *SIBLINGS , *CHORIONIC gonadotropins , *UROLOGICAL surgery , *SEX hormones , *KARYOTYPES , *MEN , *GENETIC mutation , *POSTOPERATIVE period , *TESTIS , *TESTOSTERONE , *PHENOTYPES , *GENETICS , *DIAGNOSIS , *SURGERY ,TESTIS surgery - Abstract
Persistent Müllerian Duct syndrome (PMDS) develops due to deficiency of anti-Müllerian hormone (AMH) or insensitivity of target organs to AMH in individuals with 46, XY karyotype. PMDS is characterized by normal male phenotype of external genitals, associated with persistence of Müllerian structures. This report includes the presentation of a 2.5 year old male patient due to bilateral undescended testis. His karyotype was 46, XY. The increase in testosterone following human chorionic gonadotropin stimulation test was normal. The patient was referred to our clinic after uterine, fallopian tube and vaginal remnants were recognized during the orchiopexy surgery. The family reported that the eight year old elder brother of the patient was operated on for right inguinal hernia and left undescended testis at the age of one year. A right transverse testicular ectopia was found in the elder brother. Both cases had normal AMH levels. AMHR2 gene was analyzed and a homozygous NM_020547.3:c.233-1G>A mutation was found that was not identified previously. In conclusion, we determined a novel mutation in the AMHR2 gene that was identified for the first time. This presented with different phenotypes in two siblings. [ABSTRACT FROM AUTHOR] more...
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- 2018
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23. Aromatase Deficiency due to a Novel Mutation in CYP19A1 Gene.
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Unal, Edip, Yıldırım, Ruken, Taş, Funda Feryal, Demir, Vasfiye, Onay, Hüseyin, and Haspolat, Yusuf Kenan
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- *
DIAGNOSIS of deficiency diseases , *DEFICIENCY diseases , *OVARY abnormalities , *ESTRADIOL , *FOLLICLE-stimulating hormone , *KARYOTYPES , *GENETIC mutation , *OVARIES , *PELVIS , *SEX differentiation disorders , *TESTOSTERONE , *VIRILISM , *OVARIAN cysts , *AROMATASE , *CYTOCHROME P-450 , *PREGNANCY , *GENETICS , *DIAGNOSIS - Abstract
Aromatase deficiency is a rare autosomal recessive genetic disorder with an unknown incidence. Aromatase converts androgens into estrogen in the gonadal and extra-gonadal tissues. Aromatase deficiency causes ambiguous genitalia in the female fetus and maternal virilization (hirsutism, acne, cliteromegaly, deep voice) during pregnancy due to increased concentration of androgens. A 19 months old girl patient was assessed due to presence of ambiguous genitalia. There were findings of maternal virilization during pregnancy. The karyotype was 46, XX. Congenital adrenal hyperplasia was not considered since adrenocorticotropic hormone, cortisol, and 17-hydroxyprogesterone levels were within normal ranges. At age two months, follicle-stimulating hormone and total testosterone levels were elevated and estradiol level was low. Based on these findings, aromatase deficiency was suspected. A novel homozygous mutation IVS7-2A>G (c.744-2A>G) was identified in the CYP19A1 gene. Pelvic ultrasound showed hypoplasic ovaries rather than large and cystic ovaries. We identified a novel mutation in the CYP19A1 gene in a patient who presented with ambiguous genitalia and maternal virilization during pregnancy. Presence of large and cystic ovaries is not essential in aromatase deficiency. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
24. Evaluation of QT dispersion and Tp‐e interval in children with subclinical hypothyroidism.
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Akın, Alper, Unal, Edip, Yıldırım, Ruken, Ture, Mehmet, Balık, Hasan, and Haspolat, Yusuf Kenan
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COMPARATIVE studies ,ELECTROPHYSIOLOGY ,HEART conduction system ,HYPOTHYROIDISM ,PROBABILITY theory ,THYROTROPIN ,THYROXINE ,TRIIODOTHYRONINE ,DESCRIPTIVE statistics - Abstract
Abstract: Background: Studies on adults have shown increased dispersion of QT and corrected QT (QTc), peak‐to‐end interval of the T wave (Tp‐e), Tp‐e/QT ratio, and Tp‐e/QTc ratio in subclinical hypothyroidism (SH), but there have been no pediatric studies. Materials and methods: A total of 40 SH patients were compared with 40 healthy children in respect to serum thyroid‐stimulating hormone (TSH), serum‐free level of triiodothyronine, and free level of thyroxine (fT4). SH diagnosis was accepted as TSH above the laboratory accepted upper limit (>4.2 mU/L) and normal fT4 values. The patient and control group data were compared by calculating the QT interval, QTc, QT dispersion (QTd), QTc dispersion (QTcd), Tp‐e, Tp‐e/QT ratio, and Tp‐e/QTc ratio on 12‐lead surface electrocardiogram. Results: The mean age was 7.91 ± 3.6 years in the SH group and 8.8 ± 2.4 years in the control group. In the SH group, the minimum QT (QTmin) was determined to be statistically significantly lower (P < 0.001) and maximum QT (QTmax), QTd, QTcd, Tp‐e, Tp‐e/QT ratio, and Tp‐e/QTc ratio were statistically significantly higher (P = 0.028, P < 0.001, P = 0.003, P < 0.001, P = 0.001, P < 0.001, respectively). A positive correlation was determined between TSH and QTmax (r: +0.331, P = 0.037). Conclusions: The current study is the first to have shown significantly increased QTd, QTcd, Tp‐e, Tp‐e/QT ratio, and Tp‐e/QTc ratio in children diagnosed with SH. A positive correlation was determined between TSH and maximum QT values, Tp‐e, Tp‐e/QT ratio, and Tp‐e/QTc ratio. These results suggest the need to further assess the long‐term risks of prolonged QT dispersion in the setting of subclinical hypothyroidism. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
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25. GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis-van Creveld syndrome.
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Palencia-Campos, Adrian, Ullah, Asmat, Nevado, Julian, Yıldırım, Ruken, Unal, Edip, Ciorraga, Maria, Barruz, Pilar, Chico, Lucia, Piceci-Sparascio, Francesca, Guida, Valentina, De Luca, Alessandro, Kayserili, Hülya, Ullah, Irfan, Burmeister, Margit, Lapunzina, Pablo, Ahmad, Wasim, Morales, Aixa V., and Ruiz-Perez, Victor L. more...
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- 2017
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26. Association of Subclinical Hypothyroidism with Dyslipidemia and Increased Carotid Intima-Media Thickness in Children.
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Unal, Edip, Akın, Alper, Yıldırım, Ruken, Demir, Vasfiye, Yildiz, İsmail, and Haspolat, Yusuf Kenan
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HYPOTHYROIDISM diagnosis ,CAROTID artery ,BLOOD testing ,BODY weight ,CHOLESTEROL ,STATISTICAL correlation ,ENDOCRINOLOGY ,FASTING ,HIGH density lipoproteins ,HYPERLIPIDEMIA ,LIPOPROTEINS ,LOW density lipoproteins ,PEDIATRICS ,THYROTROPIN ,CONTROL groups ,DATA analysis software ,DESCRIPTIVE statistics ,MANN Whitney U Test ,ANATOMY - Abstract
Objective: Subclinical hypothyroidism (SH) is defined as an elevated serum thyroid-stimulating hormone (TSH) level with free thyroxine (fT
4 ) level in the normal range. There are very few studies in the literature reporting on the effect of SH on lipid metabolism and carotid intima-media thickness (CIMT) in children. Methods: The study included 38 children diagnosed with SH and a control group comprising 38 healthy, euthyroid children. SH was diagnosed based on an elevated TSH level (4.2-20 mIU/L) and normal fT4 level measured in two morning fasting blood samples obtained at an interval of 2 to 6 weeks. Blood samples were collected by venipuncture in the morning after an overnight fast. Results: The patient group included 38 children (16 male, 22 female) with SH and the control group -38 healthy, euthyroid children (20 male, 18 female). Mean age was 8.1±3.6 (range, 3.5-15) years in the patient group and 8.9±2.4 (range, 4.5-15) years in the control group. In the patient group, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C), and LDL-C/HDL-C were higher compared to the control group (p=0.049, p=0.014, p=0.002, and 0.003, respectively). In the patient group, CIMT was also significantly higher compared to the control group (p=0.001). The patient group was further divided into two subgroups based on their serum TSH level: (I) patients with mildly elevated TSH (TSH=4.2±10 mIU/L) (n=33) and (II) patients with high TSH (TSH=10 mIU/L) (n=5). However, no significant difference was found between the patients with mild and severe SH with regard to TC, LDL-C, HDL-C, triglyceride level and CIMT levels (p=0.635, p=0.424, p=0.310, p=0.342, and 0.610, respectively). Conclusion: Subclinical hypothyroidism leads to increased dyslipidemia (increased TC and LDL) and increased CIMT, which leads to increased risk of cardiovascular disease. Further studies are needed to substantiate these findings in children with SH. [ABSTRACT FROM AUTHOR] more...- Published
- 2017
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27. Subclinical hypothyroidism and long QT.
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Akın, Alper, Unal, Edip, Yıldırım, Ruken, Türe, Mehmet, Balık, Hasan, and Haspolat, Yusuf Kenan
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LONG QT syndrome diagnosis ,ELECTROCARDIOGRAPHY ,HYPOTHYROIDISM in children - Published
- 2018
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28. Tip 1 Diyabetes Mellituslu Çocuklarda Tanı Anındaki Klinik ve Laboratuvar Bulgularının Değerlendirilmesi.
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Aras, Burhan, Akın, Alper, Yıldırım, Ruken, Unal, Edip, and Haspolat, Yusuf Kenan
- Abstract
Objective: The aim of our study is to evaluation of clinical and laboratory findings at the time of diagnosis in children with Type 1 Diabetes Mellitus (T1DM). Methods: In this study, 142 children diagnosed with T1DM who were referred to Pediatric Endocrinology Policlinic and Emergency Policlinic of Dicle University Medical Faculty between 2013 and 2016 were evaluated. Retrospectively, the sociodemographic characteristics, symptoms and laboratory findings of the patients were recorded from the files. All the data obtained were evaluated statistically. Results: Sixty two (43.66%) of the patients were girls. The mean age was 10,10 ± 1,39 years. The blood glucose level at diagnosis was 425,85 ± 12,51 mg/dl and HbA1c was 13,57 ± 3,77. Anti-Glutamate Decarboxylase (anti-GAD) positivity was detected in 47.8% of the cases. 18.3% of the patients had a T1DM story in their family. Patients were diagnosed mostly in January (12.6%) and November (11.9%). 83.8% of cases had both polyuria and polydipsia, 41.5% had consciousness level change and 6.3% had coma. Ketoacidosis was present in 43% of the patients at the time of admission, ketosis in 48.5% and only hyperglycemia in 8.5%. Conclusion: Type 1 DM is mostly observed in adolescence. The most common symptoms of the disease are polyuria and polydipsia. For this reason the community needs to be educated that polyuria and polydipsia may have T1DM findings. Awareness of the community in this issue can reduce the frequency of diabetic ketoacidosis, the most important complication of diabetes. [ABSTRACT FROM AUTHOR] more...
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- 2019
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29. Complete Androgen Insensitivity Syndrome; the Importance of Family Screening.
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Yıldırım, Ruken, Haspolat, Yusuf Kenan, and Helvacıoğlu, Didem
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- *
ANDROGEN-insensitivity syndrome , *MEDICAL screening - Abstract
An abstract of the article "Complete Androgen Insensitivity Syndrome; the Importance of Family Screening," by Ruken Yıldırım, Yusuf Kenan Haspolat, and Didem Helvacıoğlu is presented.
- Published
- 2015
30. A Case of Thyroid Hormone Resistance.
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Yıldırım, Ruken, Haspolat, Yusuf Kenan, Deniz, Handan, and Can, Fırat
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- *
GENETIC disorders , *HORMONE resistance , *THYROID hormones - Abstract
An abstract of the article "A Case of Thyroid Hormone Resistance," by Handan Deniz and colleagues is presented.
- Published
- 2015
31. Obez Çocuk ve Adölesanlarda Tiroid Fonksiyonlarının Değerlendirilmesi.
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Unal, Edip, Taş, Funda Feryal, Kaya, Mustafa Mesut, Yıldırım, Ruken, Aktar, Fesih, and Haspolat, Yusuf Kenan
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THYROID gland function tests , *OVERWEIGHT persons - Abstract
Background: The aim of this study was to evaluate the relationship between thyroid functions and metabolic and anthropometric parameters in obese children and adolescents. Methods: The study included 147 patients diagnosed with exogenous obesity in the pediatric endocrinology outpatient clinic and 46 healthy subjects with similar age and sex. Obese patients were divided into two groups as Group 1 (non-fatty liver) and Group 2 (with fatty liver). Fasting glucose, insulin, total cholesterol, triglyceride, aspartate aminotransferase, alanine aminotransferase, thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) samples were performed from all cases in patient groups and control group (Group 3). Insulin resistance was assessed by HOMA-IR (Homeostatic Model Assessment of Insulin Resistance). Results: In Group 2, waist circumference (WC), body mass index-standard deviation scores (SDS), hip circumference (HC), WC/HC ratio and triglyceride, fasting insulin and HOMA-IR values were significantly higher than Group 1 and Group 3 while high density lipoprotein cholesterol level was lower. In Group 1 and Group 2, fT4 level was significantly lower than Group 3, whereas fT3 /fT4 ratio was higher. The mean TSH level was higher in Group 2 than Group 3. fT3 / fT4 ratio; WC, WC / HC ratio was positively correlated with fasting insulin and HOMA-IR. Conclusion: We found that fT4 level was low and fT3 / fT4 ratio was higher in obese children. Considering the high fT3 / fT4 ratio in obese children, this ratio should be stimulating for the clinician regarding the complications associated with visceral adipose tissue as it is positively correlated with WC and insulin resistance. [ABSTRACT FROM AUTHOR] more...
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- 2019
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32. Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.
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Akalın A, Özalkak Ş, Yıldırım R, Karakaya AA, Kolbaşı B, Durmuşalioğlu EA, Kökali F, Ürel-Demir G, Öz V, Ünal E, Atik T, Şimşek-Kiper PÖ, and Elcioglu NH
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- Humans, Male, Female, Turkey, Infant, Child, Preschool, Child, Muscle Hypotonia genetics, Muscle Hypotonia diagnosis, Phenotype, Extracellular Matrix Proteins genetics, Infant, Newborn, Carrier Proteins, Cytoskeletal Proteins, Spine abnormalities, Cullin Proteins genetics, Genetic Association Studies, Dwarfism genetics, Dwarfism diagnosis, Mutation
- Abstract
3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases. A total of 25 patients from 19 unrelated families were included in the study. Genetic etiology was determined in probands through the utilization of Sanger sequencing and/or targeted gene panel analysis. The clinical, laboratory, and genetic features of all patients at admission and during follow-up were documented. Genotype-phenotype correlation was carried out in the CUL7 and OBSL1 groups. The genetic etiology was established in all patients (n = 25/25, 100%). We identified 15 distinct variants in CUL7, OBSL1, and CCDC8 genes, with eleven being novel. CUL7 variants were present in 13 patients (n = 13/25, 52%), while OBSL1 variants were found in 11 patients (n = 11/25, 44%). No notable distinctions were found in mean birth weight, height, and standard deviation scores between the CUL7 and OBSL1 mutation groups (p > 0.05). Patients with CUL7 variants exhibited significantly lower height standard deviation scores both at admission and at the last examination, as well as lower weight standard deviation scores at the last examination, compared to those with OBSL1 variants (p < 0.05)., Conclusion: To date, genotype-phenotype correlations have been identified in a limited number of studies. Further research involving larger cohorts is necessary to solidify these correlations., What Is Known: • 3M syndrome is a well-known skeletal dysplasia caused by biallelic pathogenic variants in CUL7, OBSL1, and CCDC8 genes. • Despite genetic heterogeneity, clinical, and radiologic features show homogeneity in affected individuals., What Is New: • Genotype-phenotype correlations have been established in limited studies. • The CUL7 group exhibited significantly lower height SDS at both admission and the final evaluation and lower weight SDS at the final examination compared to the OBSL1 group. • The frequency of variants in the OBSL1 gene among Turkish patients exceeds the rates reported in the literature. • Gradenigo syndrome is being reported for the first time in a patient with 3M syndrome., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Health Sciences, Diyarbakir Gazi Yasargil Training and Research Hospital Noninvasive Clinical Research Ethical Committee (approval number: 2024/69). Consent to participate: Written informed consent was obtained from the parents. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...
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- 2024
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33. Evaluation of Growth Characteristics and Final Heights of Cases Diagnosed with Noonan Syndrome on GH Treatment.
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Şıklar Z, Berberoğlu M, Kızılcan Çetin S, Yıldız M, Turan S, Darcan Ş, Çetinkaya S, Hatipoğlu N, Yıldırım R, Demir K, Vermezoğlu Ö, Yavaş Abalı Z, Özalp Kızılay D, Görkem Erdoğan N, Şiraz ÜG, Orbak Z, Özgen İT, Bideci A, Selver Eklioğlu B, Karakılıç Özturan E, Tarçın G, Bereket A, and Darendeliler F more...
- Abstract
Introduction: Proportional short stature is one of the most important features of Noonan Syndrome, and adult height often remains below the 3rd percentile. Although the pathophysiology of short stature in NS patients is not fully understood, it has been shown that GH treatment is beneficial in NS, and it significantly improves the height in respect to the results of short and long-term GH treatment., Methods: In this study, the efficacy of GH therapy was evaluated in children and adolescents with Noonan syndrome who attained final height. In this national cohort study, 67 cases with NS who reached final height from 14 centers were evaluated., Results: A total of 53 cases (mean follow-up time 5.6 years) received GH treatment. Height SDS of the subjects who were started on GH tended to be shorter than those who did not receive GH (-3.26± 1.07 vs. -2.53 ±1.23) at initial presentation. The mean final height and final height SDS in girls using GH vs those not using GH were 150.1 cm and -2.17 SD vs 47.4 cm and-2.8 SD, respectively. The mean final height and final height SDS in boys using GH vs. not using GH were 162.48 ± 6.19 cm and -1.81 SD vs 157.46 ± 10.16 cm and -2.68 ± 1.42 SD, respectively. The Δheight SDS value of the cases was significantly higher in the group receiving GH than in those not receiving GH (1.36 ± 1.12 SD vs. -0.2 ± 1.24, p<0.001). Cardiac findings remained stable in two patients with hypertrophic cardiomyopathy who received GH treatment. No significant side effects were observed in the cases during follow-up., Conclusion: In patients with Noonan syndrome who reach their final height, a significant increase in height is observed with GH treatment, and an increase of approximately +1.4 SDS can be achieved. It has been concluded that GH treatment is safe and effective. more...
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- 2024
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34. Inequalities in Access to Diabetes Technologies in Children with Type 1 Diabetes: A Multicenter, Cross-sectional Study from Türkiye.
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Karakus KE, Sakarya S, Yıldırım R, Özalkak Ş, Özbek MN, Yıldırım N, Delibağ G, Eklioğlu BS, Haliloğlu B, Aydın M, Kırmızıbekmez H, Gökçe T, Can E, Eviz E, Yeşiltepe-Mutlu G, and Hatun Ş
- Abstract
Objective: To determine inequalities in access to diabetes technologies and the effect of socioeconomic factors on families with children with type 1 diabetes., Methods: In this multicenter cross-sectional study, parents of children with type 1 diabetes completed a questionnaire about household sociodemographic characteristics, latest HbA1c values, continuous glucose monitoring (CGM) and insulin pump use of children, the education and working status of parents. These characteristics were compared between technology use (only-CGM, only-pump, CGM+pump, no technology use)., Results: Among 882 families, only-CGM users, only-pump users, and CGM+pump users compared with no technology users, adjusting for age, sex, region, education levels, number of working parents, and household income. Children living in the least developed region had lower odds of having only-CGM (OR=0.20, 95%CI 0.12-0.34) and having CGM+pump (OR=0.07, 95%CI 0.03-0.22) compared with those living in the most developed region. Children with parents who had not finished high school had lower odds of having only-CGM (Mothers: OR=0.36, 95%CI 0.19-0.66; fathers: OR=0.32, 95%CI 0.18-0.60) or both CGM+pump (OR=0.27, 95%CI 0.11-0.64; fathers: OR=0.34, 95%CI 0.15-0.79) rather than no-technology compared to children whose parents has a university degree. Every $840 increase in the household income increased the odds by 5% for having only-CGM (OR=1.05, 95%CI 1.02-1.09) and CGM+pump (OR=1.05, 95%CI 1.01-1.08)., Conclusion: Socioeconomic factors such as education, regions, and income were associated with inequality in access to technologies. The inequalities are more prominent in access to CGM while CGM had a bigger contribution to glycemic control. more...
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- 2024
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35. Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.
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Altunoglu U, Palencia-Campos A, Güneş N, Turgut GT, Nevado J, Lapunzina P, Valencia M, Iturrate A, Otaify G, Elhossini R, Ashour A, K Amin A, Elnahas RF, Fernandez-Nuñez E, Flores CL, Arias P, Tenorio J, Chamorro Fernández CI, Güven Y, Özsu E, Eklioğlu BS, Ibarra-Ramirez M, Diness BR, Burnyte B, Ajmi H, Yüksel Z, Yıldırım R, Ünal E, Abdalla E, Aglan M, Kayserili H, Tuysuz B, and Ruiz-Pérez V more...
- Subjects
- Humans, Male, Female, Child, Membrane Proteins genetics, Mutation, Child, Preschool, Zinc Finger Protein Gli3 genetics, Adolescent, Adult, Nerve Tissue Proteins genetics, Cohort Studies, Infant, Proteins genetics, Retrospective Studies, Intercellular Signaling Peptides and Proteins, Ellis-Van Creveld Syndrome genetics, Ellis-Van Creveld Syndrome pathology, Phenotype, Pedigree
- Abstract
Background: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2 . Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum., Methods: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays., Main Results: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3 , respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC., Conclusions: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC / EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.) more...
- Published
- 2024
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36. Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic > KRAS Variation.
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Demir S, Yaşar Köstek H, Sanrı A, Yıldırım R, Özgüç Çömlek F, Yalçıntepe S, Deveci M, Atlı Eİ, Atlı E, Eker D, Gürkan H, and Tütüncüler Kökenli F
- Abstract
Introduction: Germline pathogenic variations of the genes encoding the components of the Ras-MAPK pathway are found to be responsible for RASopathies, a clinically and genetically heterogeneous group of diseases. In this study, we aimed to present the results of patients genetically investigated for RASopathy-related mutations in our Genetic Diagnosis Center., Methods: The results of 51 unrelated probands with RASopathy and 4 affected relatives (31 male, 24 female; mean age: 9.327 ± 8.214) were included in this study. Mutation screening was performed on DNA samples from peripheral blood of the patients either by Sanger sequencing of PTPN11 hotspot regions (10/51 probands), or by a targeted amplicon next-generation sequencing panel (41/51 probands) covering the exonic regions of BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, RASA2, RIT1, SHOC2, SOS1, SOS2, SPRED1 , and KAT6B genes., Results: Pathogenic/likely pathogenic variations found in 22 out of 51 probands (43.13%) and their 4 affected family members were located in PTPN11, BRAF, KRAS, NF1, RAF1, SOS1 , and SHOC2 genes. The c.148A>C (p.Thr50Pro) variation in the KRAS gene was a novel variant detected in a sibling in our patient cohort. We found supportive evidence for the pathogenicity of the NF1 gene c.5606G>T (p.Gly1869Val) variation which we defined in an affected boy who inherited the mutation from his affected father., Conclusion: Although PTPN11 is the most frequently mutated gene in our patient cohort, as in most previous reports, different mutation distribution among the other genes studied motivates the use of a next-generation sequencing gene panel including the possible responsible genes., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.) more...
- Published
- 2022
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37. YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.
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De Franco E, Lytrivi M, Ibrahim H, Montaser H, Wakeling MN, Fantuzzi F, Patel K, Demarez C, Cai Y, Igoillo-Esteve M, Cosentino C, Lithovius V, Vihinen H, Jokitalo E, Laver TW, Johnson MB, Sawatani T, Shakeri H, Pachera N, Haliloglu B, Ozbek MN, Unal E, Yıldırım R, Godbole T, Yildiz M, Aydin B, Bilheu A, Suzuki I, Flanagan SE, Vanderhaeghen P, Senée V, Julier C, Marchetti P, Eizirik DL, Ellard S, Saarimäki-Vire J, Otonkoski T, Cnop M, and Hattersley AT more...
- Subjects
- Cell Line, Female, Human Embryonic Stem Cells metabolism, Human Embryonic Stem Cells pathology, Humans, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells pathology, Infant, Newborn, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells pathology, Male, Neurons metabolism, Neurons pathology, Diabetes Mellitus embryology, Diabetes Mellitus genetics, Diabetes Mellitus pathology, Endoplasmic Reticulum Stress genetics, Genetic Diseases, Inborn embryology, Genetic Diseases, Inborn genetics, Genetic Diseases, Inborn pathology, Infant, Newborn, Diseases embryology, Infant, Newborn, Diseases genetics, Infant, Newborn, Diseases pathology, Microcephaly embryology, Microcephaly genetics, Microcephaly pathology, Mutation, Vesicular Transport Proteins genetics, Vesicular Transport Proteins metabolism
- Abstract
Neonatal diabetes is caused by single gene mutations reducing pancreatic β cell number or impairing β cell function. Understanding the genetic basis of rare diabetes subtypes highlights fundamental biological processes in β cells. We identified 6 patients from 5 families with homozygous mutations in the YIPF5 gene, which is involved in trafficking between the endoplasmic reticulum (ER) and the Golgi. All patients had neonatal/early-onset diabetes, severe microcephaly, and epilepsy. YIPF5 is expressed during human brain development, in adult brain and pancreatic islets. We used 3 human β cell models (YIPF5 silencing in EndoC-βH1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects β cells. Loss of YIPF5 function in stem cell-derived islet cells resulted in proinsulin retention in the ER, marked ER stress, and β cell failure. Partial YIPF5 silencing in EndoC-βH1 cells and a patient mutation in stem cells increased the β cell sensitivity to ER stress-induced apoptosis. We report recessive YIPF5 mutations as the genetic cause of a congenital syndrome of microcephaly, epilepsy, and neonatal/early-onset diabetes, highlighting a critical role of YIPF5 in β cells and neurons. We believe this is the first report of mutations disrupting the ER-to-Golgi trafficking, resulting in diabetes. more...
- Published
- 2020
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38. Nationwide Turkish Cohort Study of Hypophosphatemic Rickets
- Author
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Şıklar Z, Turan S, Bereket A, Baş F, Güran T, Akberzade A, Abacı A, Demir K, Böber E, Özbek MN, Kara C, Poyrazoğlu Ş, Aydın M, Kardelen A, Tarım Ö, Eren E, Hatipoğlu N, Büyükinan M, Akyürek N, Çetinkaya S, Bayramoğlu E, Selver Eklioğlu B, Uçaktürk A, Abalı S, Gökşen D, Kor Y, Ünal E, Esen İ, Yıldırım R, Akın O, Çayır A, Dilek E, Kırel B, Anık A, Çatlı G, and Berberoğlu M more...
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Infant, Male, Outcome Assessment, Health Care, PHEX Phosphate Regulating Neutral Endopeptidase genetics, Turkey, Calcitriol administration & dosage, Calcium-Regulating Hormones and Agents administration & dosage, Phosphates administration & dosage, Phosphates blood, Rickets, Hypophosphatemic blood, Rickets, Hypophosphatemic drug therapy, Rickets, Hypophosphatemic genetics
- Abstract
Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options., Methods: Here we present nationwide initial and follow-up data on HR., Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1
st , 2nd and 3rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group., Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed. more...- Published
- 2020
- Full Text
- View/download PDF
39. Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience
- Author
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Esen İ, Bayramoğlu E, Yıldız M, Aydın M, Karakılıç Özturhan E, Aycan Z, Bolu S, Önal H, Kör Y, Ökdemir D, Ünal E, Önder A, Evliyaoğlu O, Çayır A, Taştan M, Yüksel A, Kılınç A, Büyükinan M, Özcabı B, Akın O, Binay Ç, Kılınç S, Yıldırım R, Aytaç EH, and Sağsak E more...
- Subjects
- Adolescent, Child, Child, Preschool, Combined Modality Therapy, Disease Management, Female, Follow-Up Studies, Humans, Infant, Male, Retrospective Studies, Treatment Outcome, Antithyroid Agents therapeutic use, Thyroidectomy methods, Thyrotoxicosis therapy
- Abstract
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. more...
- Published
- 2019
- Full Text
- View/download PDF
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