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PURPOSE: 17α Hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, typically diagnosed in late adolescence with symptoms of pubertal delay and hypertension. This study aimed to determine the clinical and laboratory characteristics of 17OHD cases and gather data on disease management. METHODS: Data from 97 nationwide cases were analyzed using the CEDD-NET web system. Diagnostic, follow-up findings, and final heights of patients were evaluated. RESULTS: Mean age at admission was 13.54 ± 4.71 years, with delayed puberty as the most common complaint. Hypertension was detected in 65% at presentation; hypokalemia was present in 34%. Genetic analysis revealed Exon 1-6 homozygous deletion as the most frequent mutation, identified in 42 cases. Hydrocortisone replacement was universal; pubertal replacement was administered to 66 cases. Antihypertensive treatment was required in 57 (90%) patients. Thirty-seven cases reached final height, with an average SD of 0.015 in 46,XX and -1.43 in 46,XY. Thelarche and pubarche did not develop properly in some cases despite estradiol treatment. CONCLUSION: This study represents the largest cohort of pediatric cases of 17-hydroxylase deficiency (17OHD) documented in the literature. Hypertension and hypokalemia can serve as guiding indicators for early diagnosis.The final height is typically considered to be normal. The relationship between genotype and phenotype remains elusive. The initial genetic test for exon 1-6 deletions may be MLPA in our region.
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Hiperplasia Suprarrenal Congénita , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Hiperplasia Suprarrenal Congénita/genética , Estudios de Cohortes , Hipertensión/genética , Hipopotasemia/genética , Pubertad Tardía/genética , Esteroide 17-alfa-Hidroxilasa/genética , Turquía/epidemiologíaRESUMEN
Introduction: Craniopharyngiomas (CPG) have complex challenges in treatment due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. This study aims to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. The study also highlights the associated difficulties in their management. Methods: Sixteen centers entered 152 patients into the ÇEDD NET data system. We evaluated the clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features. Results: Of the evaluated patients, 64 were female, and 88 were male. At presentation, the mean age was 9.1 ± 3.67 (min:1.46-max:16.92) years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), nausea and vomiting (7%). The surgical procedure applied to the patients was gross total resection (GTR) in 97 cases (63.8%) and subtotal resection in 55 cases (36.2%). Radiotherapy was initiated in 11.8% of the patients. In the pathological examination, 92% of the cases were adamantinamatous type, 8% were papillary type. Postoperatively, hormone deficiencies consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated on 27 patients. The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median time of relapse was 1.82 years (range: 0.13-10.35 years). Relapse was related to longer follow-ups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 patients, neurological deficits in 13 patients, and diabetes mellitus in 5 patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative radiotherapy. It also emphasized challenges in multidisciplinary regular follow ups and suggested early interventions such as dietary restrictions and increased exercise to prevent obesity.
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Objective: Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n=3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral antidiabetic treatment. Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.
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OBJECTIVE: The aim was to analyze the incidence trend and annual average incidence change of type 1 diabetes (T1DM) in the population <18 years of age in Malatya province. MATERIALS AND METHODS: Medical files of patients followed up with T1DM in pediatric endocri- nology clinics were reviewed. The data for the child census was taken from the Turkish Statistical Institute (TUIK), and T1DM incidence was analyzed according to the calendar year, gender, and age groups. Recently diagnosed T1DM patients per 100 000 children per year were calculated. In addition, the trend in annual incidence change over the period 2007-2019 was analyzed. RESULTS: The mean incidence of T1DM during the 13 years was 13.1/105 child years (13.8/105 child years for girls and 12.4/105 child years for boys). During the 13-year follow-up period, a sig- nificant increasing trend in the incidence of T1DM was detected. The average annual percent change (AAPC) was 8.3%. According to age groups, the average AAPC was 8.1% between 0 and 4 years old, 9.4% between 5 and 9 years old, 12.1% between 10 and 14 years old, and 30.1% between 15 and 17 years old. CONCLUSION: The incidence of T1DM in children under 18 years of age in Malatya, one of the larg- est cities in the Eastern Anatolia region of Turkey, was determined as 13.1/105 child years in the last 13 years and the average annual increase rate was 8.3%.
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BACKGROUND: Nutritional rickets (NR) is still a major problem and is exacerbated by an increasing influx of immigrants. In this study, Turkish and immigrant cases followed with the diagnosis of NR in our pediatric endocrinology clinic were retrospectively evaluated. METHODS: Detailed data of cases diagnosed with NR between 2013 and 2020 and followed for at least six months were reviewed. RESULTS: In the study period, 77 cases of NR were identified. Turkish children constituted 76.6% (n=59) while 18 (23.4%) were immigrant children. The mean age at diagnosis was 8.1±7.8 months, 32.5% (n=25) were female, and 67.5% (n=52) were male. The 25-hydroxyvitamin D3 was below normal in all patients, with a mean value of 4.3±2.6 ng/mL. Parathyroid hormone (PTH) was above normal in all and the mean value was 301.7±139.3 pg/ mL. While there were 3.9 cases of NR in 10,000 endocrine clinic patients in 2013, this rate increased more than four-fold to 15.7 patients in 2019. CONCLUSIONS: Despite the vitamin D prophylaxis program in Türkiye, NR is seen significantly more frequently in recent years, which may be associated with an increasing number of refugees. High PTH levels indicate the severity of NR cases admitted to our clinic. However, clinically significant NR is only the tip of the iceberg and the true burden of subclinical rickets is unknown. Increasing compliance with the vitamin D supplementation program in refugee and Turkish children is important for the prevention of nutritional rickets.
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Refugiados , Raquitismo , Deficiencia de Vitamina D , Humanos , Niño , Masculino , Femenino , Lactante , Estudios Retrospectivos , Raquitismo/epidemiología , Raquitismo/prevención & control , Raquitismo/complicaciones , Vitamina D , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Hormona Paratiroidea/uso terapéutico , Vitaminas/uso terapéuticoRESUMEN
BACKGROUND: The increasing prevalence of childhood obesity and accompanying comorbidities all over the world constitutes one of the most important public health problems of the changing world. The frequency and causes of the metabolically healthy obesity (MHO) phenotype in children is not clear. OBJECTIVE: The objective is to determine the prevalence of the MHO phenotype in obese Turkish children and adolescents and to identify clinical and biochemical indicators for this phenotype. METHODS: Eight hundred forty-seven obese children and adolescents, aged 3-18 years with BMI-SDS >+2 SD from the obesity outpatient clinic were included. Demographic, anthropometric, and physical examination information was collected from patient medical files. In addition, obesity-related comorbidities and results of laboratory tests were obtained. For study purposes, obese patients with no cardiometabolic risk factors were accepted as MHO, and those with ≥1 cardiometabolic risk factor were considered metabolically unhealthy obese (MUO). MHO was defined according to Damanhoury's criteria. RESULTS: Out of 847 children (mean age 10.6±3.4 years) who met the study criteria, 289 (34.1%) were diagnosed with MHO. Being younger, prepubertal, having relatively low BMI, low waist/hip ratio, low insulin resistance (HOMA-IR) index, high high-density lipoprotein, low triglyceride, low fasting insulin and glucose levels, low uric acid and low alanine transaminase (ALT) levels were associated with MHO. CONCLUSIONS: The MHO phenotype was present in just over a third of this obese pediatric cohort. The most important factors associated with MHO; age, waist-hip ratio, and BMI were determined.
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OBJECTIVES: Congenital hypothyroidism (CH) is still one of the most common causes of preventable cognitive impairment in children, and its early detection and treatment prevent irreversible neurodevelopmental delay. Depending on the underlying cause, cases with CH may be transient or permanent. This study aimed to compare the developmental evaluation results of transient and permanent CH patients and to reveal any differences. METHODS: A total of 118 patients with CH, who were followed up jointly in pediatric endocrinology and developmental pediatrics clinics, were included. The patients' progress was evaluated per the International Guide for Monitoring Child Development (GMCD). RESULTS: Of the cases, 52 (44.1%) were female, and 66 (55.9%) were male. While 20 (16.9%) cases were diagnosed with permanent CH, 98 (83.1%) were diagnosed with transient CH. According to the results of the developmental evaluation made with GMCD, the development of 101 (85.6%) children was compatible with their age, while 17 (14.4%) children had delays in at least one developmental area. All 17 patients had a delay in expressive language. Developmental delay was detected in 13 (13.3%) of those with transient CH and 4 (20%) with permanent CH. CONCLUSIONS: There is difficulty in expressive language in all cases of CH with developmental delay. No significant difference was found between the developmental evaluations of permanent and transient CH cases. The results revealed the importance of developmental follow-up, early diagnosis and interventions in those children. GMCD is thought to be an important guide to help monitoring the development of patients with CH.
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Hipotiroidismo Congénito , Recién Nacido , Humanos , Masculino , Niño , Femenino , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/etiología , Tamizaje Neonatal/métodos , Pruebas de Función de la Tiroides/métodos , Desarrollo Infantil , Enfermedad Aguda , Tiroxina , TirotropinaRESUMEN
CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol synthesis, as well as an increased mineralocorticoid effect. AIM: This study aimed to evaluate the clinical, biochemical, and molecular characteristics of patients with 17OHD and to discuss the diagnosis, treatment, and follow-up process. METHODS: Age, symptoms, anthropometric measurements, blood pressure, and hormonal, biochemical, and chromosomal analysis results of 13 patients diagnosed with 17OHD between 2003 and 2022 were recorded at admission and during follow-up. Whole gene next-generation sequencing was performed for the CYP17A1 gene. Multiplex ligation-dependent probe amplification was used to detect deletions in patients without point mutations in CYP17A1. RESULTS: The median age at diagnosis was 14.0 (3.5-16.8) years. Nine of 13 patients (69.2%) had 46,XY karyotypes. All patients were phenotypically female and were raised as girls. The most common reasons for admission were the absence of puberty and amenorrhea (n = 8, 61.5%), followed by hypertension (n = 3, 23.0%), and family screening (n = 2, 15.3%). At the time of diagnosis, hypertension was detected in 10 (76.9%) patients, and 11 (84.6%) patients had hypokalemia. CONCLUSIONS: 17OHD should be considered in patients with pubertal delay/primary amenorrhea, hypertension, and hypokalemia. Adrenal function should be included in the clinical study of hypergonadotropic hypogonadism, after excluding Turner syndrome, in all 46,XX females. Deletion in the CYP17A1 gene, including exons 1-6, is the founder mutation for Turkey's east and southeast regions.
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Hiperplasia Suprarrenal Congénita , Hipertensión , Hipopotasemia , Humanos , Femenino , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Amenorrea/genética , Hipopotasemia/genética , Estudios de Seguimiento , Mutación/genética , Esteroide 17-alfa-Hidroxilasa/genética , Hipertensión/genética , ExonesRESUMEN
Objective: With the diagnosis of chronic illness in children, a stressful period is likely to begin for both the affected child and their families. The aim of this study was to investigate the factors affecting chronic disease management by the parents of children diagnosed with type 1 diabetes mellitus (T1DM). Methods: The sample consisted of 110 children, aged between 4-17 years and their mothers. The patients had been diagnosed with T1DM for at least one year, and had attended pediatric endocrinology outpatients or were hospitalized in a single center. First, sociodemographic information about the child with T1DM were obtained. Then, the "Family Management Measure" (FaMM) was applied. The FaMM is constructed to measure family functioning and management in families who have a child with a chronic illness. Results: Paternal years of education (p=0.036), family income (p=0.008), insulin pump use (p=0.011), and time elapsed after diagnosis (p=0.048) positively affected both the management of T1DM and the child's daily life. However, presence of chronic diseases in addition to T1DM (p=0.004) negatively affected diabetes management. Higher maternal education year (p=0.013) and family income level (p=0.001) increased parental mutuality scores. However, as the time after diagnosis increased, parental mutuality scores decreased. Conclusion: It is important to evaluate the child with chronic disease with a biopsychosocial approach. This approach aims to evaluate the problems of the child and his/her family who experience the disease with a holistic approach.
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Diabetes Mellitus Tipo 1 , Humanos , Niño , Masculino , Femenino , Preescolar , Adolescente , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/psicología , Madres , Enfermedad Crónica , Manejo de la Enfermedad , Melanoma Cutáneo MalignoRESUMEN
Objective: Idiopathic hypogonadotropic hypogonadism (IHH) is classified into two groups-Kalman syndrome and normosmic IHH (nIHH). Half of all cases can be explained by mutations in >50 genes. Targeted gene panel testing with nexrt generation sequencing (NGS) is required for patients without typical phenotypic findings. The aim was to determine the genetic etiologies of patients with IHH using NGS, including 54 IHH-associated genes, and to present protein homology modeling and protein stability analyzes of the detected variations. Methods: Clinical and demographic data of 16 patients (eight female), aged between 11.6-17.8 years, from different families were assessed. All patients were followed up for a diagnosis of nIHH, had normal cranial imaging, were without anterior pituitary hormone deficiency other than gonadotropins, had no sex chromosome anomaly, had no additional disease, and underwent genetic analysis with NGS between the years 2008-2021. Rare variants were classified according to the variant interpretation framework of the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology. Changes in protein structure caused by variations were modeled using RoseTTAFold and changes in protein stability resulting from variation were analyzed. Results: Half of the 16 had no detectable variation. Three (18.75%) had a homozygous (pathogenic) variant in the GNRHR gene, one (6.25%) had a compound heterozygous [likely pathogenic-variants of uncertain significance (VUS)] variant in PROK2 and four (25%) each had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH. Conclusion: The frequency of variation detection was similar to the literature. Modelling showed that the variant in five different genes, interpreted as VUS according to ACMG, could explain the clinical IHH.
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Hipogonadismo , Humanos , Femenino , Niño , Adolescente , Hipogonadismo/genética , Hipogonadismo/diagnóstico , Mutación , Fenotipo , HeterocigotoRESUMEN
OBJECTIVE: The effect of subclinical hypothyroidism on glucose and lipid metabolism in obese children is controversial. This study aims to compare cardiovascular risk factors in obese patients with or without subclinical hypothyroidism and determine the frequency of subclinical hypothyroidism in obese children and adolescents. MATERIALS AND METHODS: A total of 1130 obese children and adolescents aged 6-18 years were included in this single-center cross-sectional study. Metabolic parameters such as thyrotropin, free thyroxine, free triiodothyronine, homeostasis model assessment for insulin resistance, atherogenic index, and lipids were evaluated. The patients were divided into two groups-subclinical hypothyroidism group (free thyroxine normal, thyroid-stimulating hormone 5.5-10 mIU/L) (n = 59) and the control group (free thyroxine normal, thyroid-stimulating hormone < 5 mIU/L) (n = 1071). RESULTS: Subclinical hypothyroidism was detected in 59 (5.2%) of 1130 patients. The mean body mass index was similar in both groups. The mean serum insulin, homeostasis model assessment for insulin resistance, triglyceride, atherogenic index of plasma, aspartate aminotransferase, and alanine aminotransferase levels were higher in the subclinical hypothyroidism group, and the mean high-density lipoprotein cholesterol level was lower than the control group (P = .005, P < .001, P = .028, P < .001, P = .001, P < .001, and P = .018, respectively). While a positive correlation was observed between the thyroid-stimulating hormone levels and insulin, homeostasis model assessment for insulin resistance, alanine aminotransferase, triglyceride, and basal cortisol levels, a negative correlation was found between thyroid-stimulating hormone and highdensity lipoprotein cholesterol. CONCLUSION: Subclinical hypothyroidism can negatively affect the lipid and glucose profile.
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BACKGROUND: The study aim was to examine changes in trends of presenting features during the diagnosis of patients followed up with newly diagnosed Type 1 diabetes mellitus (T1DM) over the past 24 years. METHODS: The study was retrospective. Patients with a diagnosis of T1D between the years of 1996-2019 were included. Patients diagnosed in the first half of the period comprised Period I, and those from the second half comprised Period II. Patient data were extracted from medical records and included gender distribution, year of diagnosis, age at diagnosis, duration of symptoms, type of admission, frequency of diabetic ketoacidosis (DKA) and biochemical parameters. Subsequently, temporal changes in trends of these parameters were sought. RESULTS: For the whole cohort the gender distribution was equal; 404 (49.6%) were girls and 410 (50.4%) were boys. Mean age at diagnosis was 8.5±4.2 years and age groupings at presentation were: 23.2% (n = 189) aged 0-4; 39.2% (n = 319) aged 5-9; 27.5% (n = 224) aged 10-13; 10.1% (n= 82) aged 14-18. At presentation 72 (12.7%) had hyperglycemia, 230 (40.6%) had diabetic ketosis, and 264 (46.6%) had DKA. In those with DKA, mild DKA was found in 103 (39.0%), moderate DKA in 81 (30.6%), and severe DKA in 80 (30.3%). While the frequency of DKA was 54.9% between 1996 and 2007 (Period I), this significantly decreased to 44.4% between 2008 and 2019 (Period II). Girls and boys had a similar rate of T1DM, and this did not change over time. Three peak ages of diagnosis were evident; 5-7, 8-10, 12-14 years of age. CONCLUSIONS: The frequency of DKA decreased and the frequency of admission with hyperglycemia and ketosis increased during the study period, which may have repercussions for mortality and morbidity rates and aid in improved treatment outcomes.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Hiperglucemia , Adolescente , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/epidemiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Turquía/epidemiologíaRESUMEN
OBJECTIVES: The aim of the study was to determine the prevalence of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and other comorbidities in overweight and obese children in Malatya, Turkey. METHODS: Retrospective cross-sectional study. We studied 860 obese and overweight children and adolescents (obese children Body mass index (BMI) >95th percentile, overweight children BMI >85th percentile) aged between 6 and 18 years. The diagnosis of MetS, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and T2DM were defined according to modified the World Health Organization criteria adapted for children. Other comorbidities were studied. RESULTS: Subjects (n=860) consisted of 113 overweight and 747 obese children of whom 434 (50.5%) were girls. MetS was significantly more prevalent in obese than overweight children (43.8 vs. 2.7%, p<0.001), and in pubertal than prepubertal children (41.1 vs. 31.7%, p<0.001). Mean homeostasis model assessment for insulin ratio (HOMA-IR) was 3.6 ± 2.0 in the prepubertal and 4.9 ± 2.4 in pubertal children (p<0.001). All cases underwent oral glucose tolerance test and IGT, IFG, and T2DM were diagnosed in 124 (14.4%), 19 (2.2%), and 32 (3.7%) cases, respectively. Insulin resistance (IR) was present in 606 cases (70.5%). CONCLUSIONS: Puberty and obesity are important risk factors for MetS, T2DM, and IR. The prevalence of MetS, T2DM, and other morbidities was high in the study cohort. Obese children and adolescents should be carefully screened for T2DM, insulin resistance, hyperinsulinism, dyslipidemia, hypertension, IGT, and IFG. The prevention, early recognition, and treatment of obesity are essential to avoid associated morbidities.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Obesidad Infantil , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/etiología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Sobrepeso/metabolismo , Obesidad Infantil/complicaciones , Obesidad Infantil/epidemiología , Prevalencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Congenital hypothyroidism (CH) is the most common cause of preventable but irreversible mental retardation in children, although the risk has been widely abolished by national neonatal screening programs. The aim of this study was to determine, (a) the cause of CH, (b) the etiological cause of persistent CH and (c) to investigate the role of laboratory and clinical data in predicting persistent and transient CH. METHODS: Patients diagnosed with CH, who started L-thyroxine treatment and were followed up for at least three years were included. Patient data were reviewed retrospectively. Serum thyroid hormones were measured four weeks after discontinuation of therapy at age three or earlier. Cases with a thyroid-stimulating hormone (TSH) value of >10 mIU/mL were accepted as permanent hypothyroidism, while cases with normal TSH values for six months after cessation were accepted as transient hypothyroidism. RESULTS: There were 232 treated cases, of whom 108 (46.6%) were female, and 169 (72.8%) were eventually diagnosed with transient CH. The best cut-off point for predicting permanent status was determined as LT4 cut-off dose ≥1.45 mcg/kg/day. The median (range) duration of L-thyroxine treatment in transient hypothyroid cases was 24 (range: 6-36) months, and treatment was discontinued before the age of three years in 64%. DISCUSSION: There were 232 treated cases, of whom 108 (46.6%) were female, and 169 (72.8%) were eventually diagnosed with transient CH. The best cut-off point for predicting permanent status was determined as LT4 cut-off dose ≥1.45 mcg/kg/day. The median (range) duration of L-thyroxine treatment in transient hypothyroid cases was 24 (range: 6-36) months, and treatment was discontinued before the age of three years in 64%.
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Hipotiroidismo Congénito , Tiroxina , Recién Nacido , Niño , Humanos , Femenino , Preescolar , Masculino , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/tratamiento farmacológico , Estudios Retrospectivos , Hormonas Tiroideas , Tirotropina , Tamizaje Neonatal/efectos adversosRESUMEN
Objective: Primary adrenal insufficiency (PAI) is a rare but potentially life-threatening condition. In childhood, PAI is usually caused by monogenic diseases. Although congenital adrenal hyperplasia (CAH) is the most common cause of childhood PAI, numerous non-CAH genetic causes have also been identified. Methods: Patients aged 0-18 years and diagnosed with PAI between 1998 and 2019 in a tertiary care hospital were retrospectively evaluated. After the etiologic distribution was determined, non-CAH PAI patients were evaluated in detail. Results: Seventy-three PAI patients were identified. The most common etiology was CAH (69.9%, n=51). Non-CAH etiologies accounted for 30.1% (n=22) and included adrenoleukodystrophy (ALD; n=8), familial glucocorticoid deficiency (n=3), Triple A syndrome (n=5), autoimmune adrenalitis (n=1), adrenal hypoplasia congenital (n=1), IMAGe syndrome (n=1), and other unknown etiologies (n=3). The median age at the time of AI diagnosis for non-CAH etiologies was 3.52 (0.03-15.17) years. The most frequent symptoms/clinical findings at onset were hyperpigmentation of skin (81.8%), symptoms of hypoglycemia (40.9%), and weakness/fatigue (31.8%). Hypoglycemia (50.0%), hyponatremia (36.4%) and hyperkalemia (22.7%) were prominent biochemical findings. Diagnosis of specific etiologies were proven genetically in 13 of 22 patients. A novel p.Q301* hemizygous frameshift mutation of the DAX1 gene was identified in one patient. Conclusion: Etiology was determined in 86.3% of children with non-CAH PAI through specific clinical and laboratory findings with/ without molecular analysis of candidate genes. ALD was the most common etiology. Currently, advanced molecular analysis can be utilized to establish a specific genetic diagnosis for PAI in patients who have no specific diagnostic features.
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Enfermedad de Addison/diagnóstico , Enfermedad de Addison/etiología , Adolescente , Hiperplasia Suprarrenal Congénita/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
OBJECTIVE: To investigate phenotype-genotype correlations in Turkish children with glucokinase gene mutations leading to Maturity-onset diabetes in young (GCK-MODY). METHODS: Retrospective analysis of 40 patients (16 girls) aged under 18 with GCK-MODY. RESULTS: Mean (SD) serum fasting blood glucose level was 6.79 (0.59) mmol/L and the mean (SD) HbA1c level at diagnosis was 6.3% (0.5). Sixteen different variations were detected in the GCK genes of the 40 cases; 33 missense mutations, 6 deletions, and one nonsense mutation. The birthweight of infants with deletion mutation was significantly lower than that of infants with other mutations [2460 (353.66) g vs 2944.11 (502.08) g]. CONCLUSION: GCK-MODY patients with deletion mutation inherited from mothers had lower birthweight and higher fasting blood glucose than those with other inherited mutations but similar HbA1c values.
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Diabetes Mellitus Tipo 2 , Glucoquinasa , Adolescente , Niño , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Femenino , Genotipo , Glucoquinasa/genética , Humanos , Masculino , Mutación , Fenotipo , Estudios RetrospectivosRESUMEN
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.
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Hiperplasia Suprarrenal Congénita/genética , Progesterona Reductasa/genética , Esteroide 11-beta-Hidroxilasa/genética , Esteroide 21-Hidroxilasa/genética , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Adolescente , Adulto , Alelos , Niño , Preescolar , Bases de Datos Genéticas , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Esteroide 11-beta-Hidroxilasa/metabolismo , Esteroide 17-alfa-Hidroxilasa/metabolismo , Esteroide 21-Hidroxilasa/metabolismo , Turquía , Adulto JovenRESUMEN
Laron syndrome, also known as growth hormone insensitivity, is an autosomal recessive disorder characterised by short stature due to mutations or deletions in the growth hormone receptor (GHR), leading to congenital insulin-like growth factor 1 (IGF1) deficiency. Cardiac abnormalities, such as patent ductus arteriosus or peripheral vascular disease are rare in patients with Laron syndrome, but cardiac hypertrophy has been observed after IGF1 therapy. In this report, we present a 10-year-and-5-month-old girl with severe peripheral-type pulmonary artery hypoplasia and Laron syndrome related to homozygous GHR c.784>C mutation.
Asunto(s)
Proteínas Portadoras/genética , Homocigoto , Síndrome de Laron/genética , Mutación , Arteria Pulmonar/anomalías , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Síndrome de Laron/diagnóstico , Fenotipo , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugíaRESUMEN
High doses of oral calcium or long-term calcium infusions are recommended to correct the hypocalcemia and secondary hyperparathyroidism in patients with hereditary 1,25 dihydroxyvitamin D3-resistant rickets (HVDRR). Preliminary studies revealed that calcimimetics may be a safe and effective therapeutic choice in children with secondary hyperparathyroidism. Our aim was to observe the efficacy of cinacalcet in the normalization of secondary hyperparathyroidism and hypophosphatemia in two siblings aged 2.5 years and 6 months with HVDRR who did not respond to traditional treatment regimes. Both patients were admitted to the hospital with severe hypocalcemia. They were treated with high doses of calcitriol and calcium infusions intravenously. Secondary hyperparathyroidism was normalized temporarily, but did not improve completely. Cinacalcet (0.25 mg/kg) once a day along with the high doses of oral calcium and calcitriol was added to the treatment schedule. After 3 months, biochemical and radiologic findings reverted to normal. Our findings indicate that cinacalcet is effective in normalizing the hyperparathyroidism and hypophosphatemia in these cases and in improving the bone pathology.
Asunto(s)
Cinacalcet/uso terapéutico , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Calcimiméticos/uso terapéutico , Preescolar , Femenino , Humanos , Hiperparatiroidismo Secundario/prevención & control , Hipofosfatemia/prevención & control , Lactante , Resultado del TratamientoRESUMEN
UNLABELLED: The aim of this study was to determine the reference ranges of lymphocyte subsets in serologically HIV-negative healthy adults in Turkey. MATERIALS AND METHODS: Blood samples from 220 healthy adults, 105 female and 115 male, collected into tubes containing EDTA were investigated for lymphocyte subsets using flow cytometry. The age range was 18-80 years (44.80 +/- 16.69). RESULTS: The mean percentage and absolute values of the lymphocyte subsets were as follows: CD3: 72.70 +/- 8.44%, 1,680 +/- 528 cells/microl; CD4: 47.37 +/- 9.10%, 1,095 +/- 391 cells/microl; CD8: 28.99 +/- 5.99%, 669 +/- 239 cells/microl; CD19: 10.96 +/- 4.44%, 254 +/- 122 cells/microl and CD56: 7.03 +/- 3.26%, 161 +/- 92 cells/microl, respectively. The ratio of CD4/CD8 was 1.68 +/- 0.43. There was no statistically significant difference in the percentages and absolute values of lymphocyte subsets between the genders (p > 0.05). CONCLUSION: Immunophenotyping has been used to establish reference values of lymphocyte subsets in normal healthy adults in Turkey.