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INTRODUCTION: Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in patients with type 1 diabetes (T1D). Children with T1D have a similar or higher prevalence of being overweight (OW) or obese (Ob) compared to healthy peers. The aim of this study was to determine the prevalence of CVD risk factors in children and adolescents with T1D and the impact of obesity and sex differences on these factors. METHODS: Data of patients aged 10-21 years and who had been using intensive insulin therapy with a diagnosis of T1D for at least three years were evaluated. Patients were divided into normal weight (NW), OW and Ob groups based on body mass index percentiles. Risk factors for CVD (obesity, dyslipidemia, hypertension) were compared between groups, and impact of gender was also analyzed. RESULTS: Data of 365 patients (200 girls, 54.8%), were evaluated. Prevalence of OW/Ob was 25.9% and was significantly higher in girls (30.6% vs 20.1%, p

INTRODUCTION: Estrogen-secreting adrenocortical tumors (ACTs) are quite rare with feminizing adrenocortical tumors (FATs) accounting for 0.37-2% of all ACTs. The aim was to evaluate clinical and hormonal characteristics of FATS as well as treatment options and follow-up in the pediatric age group. METHODS: Medical records of children with ACTs presenting to a single center in the last two decades were reviewed. Literature review within Pubmed revealed 34 pediatric patients (22 boys) with FAT among 192 articles. RESULTS: Among the 25 children presenting with ACTs in the last two decades, two new pediatric cases of FAT were identified, one benign and the other malignant, in two genders with different clinical presentations. Literature review showed that FATs are extremely rare tumors that are most commonly seen in men and boys presenting with gynecomastia. FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. While boys present with contrasexual pseudopuberty signs, girls present with isosexual pseudopuberty. A high estrogen level strongly supports diagnosis, while elevations in other adrenal hormones may be seen. FATs are usually malignant in adults and prognosis is generally very poor. However, in children approximately half are benign although assessment of malignant potential depends on clinical behavior of the tumor. FATs are very unpredictable so even after surgery long-term follow-up is required. FATs presenting in childhood may have a better prognosis than adult presentation tumors as most FATs in children are followed without recurrence of tumor. DISCUSSION AND CONCLUSION: FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. FATs in childhood may have a better prognosis than in adult males.

Objective:Initial high-dose sodium levothyroxine (Na-LT4) (10-15 μg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels.Methods:Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups.Results:Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 μg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016).Conclusion:Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pretreatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.

Objective:Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose.Methods:Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate.Results:Peak stimulated LH

Objective: Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in patients with type 1 diabetes (T1D). Children with T1D have a similar or higher prevalence of being overweight (OW) or obese (Ob) compared to healthy peers. The aim of this study was to determine the prevalence of CVD risk factors in children and adolescents with T1D and the impact of obesity and sex differences on these factors. Methods: Data of patients aged 10-21 years and who had been using intensive insulin therapy with a diagnosis of T1D for at least three years were evaluated. Patients were divided into normal weight (NW), OW and Ob groups based on body mass index percentiles. Risk factors for CVD (obesity, dyslipidemia, hypertension) were compared between groups, and impact of gender was also analyzed. Results: Data of 365 patients (200 girls, 54.8%), were evaluated. Prevalence of OW/Ob was 25.9% and was significantly higher in girls (30.6% vs 20.1%, p<0.001). Rate of hypertension was highest in OW/Ob girls followed by OW/Ob boys, and similar in NW girls and boys (p=0.003). Mean low density lipoprotein cholesterol (LDL-c) and triglyceride (TG) levels were highest in OW/Ob girls, followed by OW/Ob boys, NW girls and NW boys, respectively (p<0.001 and p<0.001, respectively). Mean high density lipoprotein-cholesterol (HDL-c) levels were similar among groups. Rates of high LDL-c and TG were similar between OW/Ob girls and boys and higher than NW girls, followed by NW boys (p<0.001 and p<0.001, respectively). The rate of low HDL-c was similar in OW/Ob girls and boys, and higher than NW girls, followed by NW boys (p<0.001). Overall, girls were 1.9 times more likely than boys to have two or more risk factors for CVD. Factors associated with risk for CVD in multiple logistic regression analyses were being a girl, followed by higher daily insulin dose, higher hemoglobin A1c, and longer duration of diabetes (r=0.856; p<0.001). Conclusion: In spite of the increased prevalence for obesity in both sexes, the trend for CVD risk factors was greater in Ob girls, followed by Ob boys and NW girls. Girls with T1D are more likely to be OW/Ob and to have CVD risk than boys, highlighting the need for early intervention and additional studies to elucidate the causes. [ABSTRACT FROM AUTHOR]

In our country, the Ministry of Health is involved in the regulation and licensure of postgraduate medical education. The Turkish Medical Association plays a role in specialist training through the Coordination Board of Specialist Associations. There are two big associations that are members of the Turkish Medical Association (The Turkish Pediatric Association, The Turkish National Pediatric Association). Modern medical education in the Ottoman Empire started on 14 March 1827. The first Turkish book on newborn care and diseases was written in 1844. Lectures by a pediatrician, at the Military Medical School began in the 1900s. With the law, which was enacted on 8 November 1928 in the Republican period, a requirement of licensure in pediatrics was determined as a two-year working period. With the 1933 university reform, the İstanbul University Medical Faculty Department of Pediatrics was established. Today, Pediatrics residency training continues to be given in 62 Medical Faculties and 29 Training and Research Hospitals, according to the quota data for the 2023 Medical Specialization Examination. In 1995, the Turkish Pediatric Association and the Turkish National Pediatric Association came together and decided to work on improving Pediatric Education in Turkey. On September 14, 2003, the General Assembly of the Turkish Pediatrics Board convened for the first time. In 2019, the board of pediatrics accelerated its work with a new perspective. In 2020, the Pediatric board started accreditation of educational programs and in 2021, two levels (Knowledge and skill exams) the National board exam. [ABSTRACT FROM AUTHOR]

Aim: Gorlin syndrome is an autosomal dominant disorder characterized by cutaneous basal cell carcinomas, odontogenic keratocysts and skeletal anomalies. Predisposition to certain types of cancers is among the main features of the disease. Chromosome instability was suspected as a mechanism for cancer predisposition. However, previous studies failed to prove the presence of chromosome instability. Materials and Methods: We present 11 patients with Gorlin syndrome. Results: Six of the patients were checked for increased sister chromatid exchange and were found normal. Two other patients had concurrent chromosome anomalies. Conclusion: Evidence for chromosome instability was not found in our patients. Occurrence of chromosome instability in a subgroup of patients and mechanisms underlying cancer predisposition requires further studies for full elucidation. Hairy patches and pigmentary skin lesions are among the recently defined common features of the syndrome.

Objective: Governments have enforced restrictions to prevent the spread of coronavirus disease 2019, which has affected lifestyle and psychosocial well-being. The aim of this study is to examine the psychosocial dimensions of children with type 1 diabetes mellitus and lifestyle changes in the face of the pandemic. Materials and Methods: Sixty school-aged children with type 1 diabetes mellitus were included to evaluate socioeconomic status, lifestyle changes, and psychological state after a 3-month school closure, using a questionnaire as well as scales in children and mothers [Depression-Anx iety-Stress Scale (short-form), Revised Child Anxiety-Depression Scale (parent-version), The Perceived Stress Scale in Children] via a Google® Form. The effect of pre-pandemic glycemic control on lifestyle and factors affecting HbA1c change were also investigated. Results: The percentage of mothers having scale scores above the cutoff in terms of stress, anxiety, and depression were 18.3%, 23.3%, and 33.3%, respectively. Mother's and children's anxiety, depression, and stress scores were positively correlated. Employed mothers had higher depression scores. Paternal unemployment increased the anxiety of the mothers. Seventy-eight percent (n = 46) of the mothers thought that diabetes in their children increased the risk of coronavirus disease 2019 infection, and children of these mothers had higher depression, anxiety, and stress scores(P = .01, P < .01, P < .01). The majority of participants were adversely affected by coronavirus disease 2019 in terms of daily routines and dietary compliance. Patients with poor-controlled type 1 diabetes mellitus deteriorated more in terms of diet compliance (P = .01). Conclusion: Coronavirus disease 2019 affects the psychosocial dimensions in the family of children with type 1 diabetes mellitus. The psychosocial impact is reflected within the family and may affect diabetic control. Thus, it should be handled within the context of family. The provision of proper information and guidance to parents may be crucial to alleviate the psychosocial burden on the family during the pandemic. [ABSTRACT FROM AUTHOR]

To the Editor: Genetic eye diseases constitute a large and heterogeneous group. Individual diseases may cause multiple structural/functional anomalies and developmental features. Family history may be suggestive; however, it may also be challenging, particularly in late-onset conditions or in cases of variable expression. In the current era of genetic advances, diagnosis of a genetic eye disease is facilitated by well-established collaboration between ophthalmologists and geneticists, as increasingly more patients will be asking for genetic counseling and prenatal diagnosis in addition to ophthalmologic management. Molecular investigation of a genetic eye disease requires customized analysis and advanced technology in addition to the requisite detailed family history and accurate ophthalmological diagnosis. A common indication for genetic testing is the validation of a preliminary diagnosis made in clinical practice. The need to determine the prognostic implications of the genotype, assessment of the recurrence risk and in particular, the possibility of specific gene therapy in the near future encourages clinicians to pursue genetic research. We present here a baseline algorithm covering common genetic mechanisms in order to outline a basic molecular approach for ophthalmologists. The first step of the flow chart, a prudent clinical examination with complete description of the phenotype, is indispensible for making a precise and accurate preliminary diagnosis (Figure 1). If the phenotype is pathognomonic, Sanger sequencing is preferred for confirmation.1 A previously established genotype-phenotype correlation may add to the value, either by providing accurate prognostic information or by indicating which particular mutation to look for. One such example may be electroretinographic supranormal rod response, indicating KCNV2 mutation type cone dystrophy, which can be precisely detected by Sanger sequencing or qPCR.2 Conventional karyotyping reveals microscopically visible abnormalities in chromosome number and structure, as well as translocations and large indels, and is appropriate as the first-tier test in multisystemic congenital abnormalities. Although conventional cytogenetic analysis may be considered as a screening test in such patients, microscopic diagnosis sometimes requires preliminary clinical diagnosis, designed in order to unveil specific deletions or duplications. A classic example is the small 11p interstitial deletion in Wilms tumor and aniridia, which could only be shown via fluorescence in situ hybridization or multiplex ligation-dependent probe amplification. Array comparative genomic hybridization methods are preferred for genetic eye diseases involving copy number variations. One such example is congenital cataract, which has a very complicated phenotype-genotype correlation and shows clinical heterogeneity. Responsible mutations in crystallins, transcription factors and membrane proteins have been reported.3 Furthermore, single nucleotide polymorphism array may enable the detection of disease predisposition or drug resistance (e.g. age-related macular degeneration). Next generation sequencing is the most current technology allowing parallel sequencing of many genes and may cover either a spectrum of known genes or all exons of all genes, allowing the discovery of new causative genes. The latter is called whole exome sequencing, and is a popular and practical investigation tool for developmental diseases.1 Genetic testing, theoretically, can also reveal the underlying ocular problem in cases with subnormal vision but otherwise normal ophthalmological examination (i.e. inherited retinal dystrophies), or it can define the high-risk group for an ocular disease and factors that prevent/delay any poor prognosis (i.e. early-onset glaucoma).4 The ultimate aim is to treat the condition. This is crucial in genetic disorders, in which modern treatment suggestions involve replacement of the missing molecular element. Many ongoing trials regarding gene therapies appear to have promising results for future treatment options.5 Ophthalmologists would benefit from a practical flow chart based on a priori assumption of genetic basis for each genetic eye disease. This would not only save time and money but may also lead to practical advances in diagnosis and management.

Objective: This study aimed to investigate the psychosocial impact of the pandemic in pediatric patients with congenital adrenal hyperplasia and their families and whether congenital adrenal hyperplasia imposes an additional burden compared to other endocrine disorders. Materials and Methods: Patients with congenital adrenal hyperplasia (n = 38) and congenital hypothyroidism (n = 41) and their families were enrolled in the prospective longitudinal survey study. Questionnaires that were completed remotely in June 2020 and in July 2021 included Depression Anxiety Stress Scale short form, The State-Trait Anxiety Inventory for Children, and purpose-built daily routine, parent, and child COVID information scores, factors affecting drug usage, and parents’ thoughts about the pandemic. At the end of 1 year, Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children were repeated in the congenital adrenal hyperplasia group and they were questioned about the incidence and severity of coronavirus infection. Results: Median Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children scores were similar between the congenital adrenal hyperplasia and congenital hypothyroidism groups. In the congenital adrenal hyperplasia group, median purpose-built daily routine was higher in those who had a State-Trait Anxiety Inventory for Children-State score above the threshold (P = .048), also Depression Anxiety Stress Scale short form-Depression, Depression Anxiety Stress Scale short form-Anxiety, Depression Anxiety Stress Scale short form-Stress, Parent COVID Information Score were higher among parents who followed news/data because of chronic diseases/medications of the child (P = .010, P = .034, P = .044, P = .045, respectively), and State-Trait Anxiety Inventory for Children-State was higher among parents who believed “having chronic diseases” and “using medications” increase the risk of COVID-19 infection (P = .011, P = .016, respectively). In the second survey, State-Trait Anxiety Inventory for Children-State, Depression Anxiety Stress Scale short form-Anxiety, and Depression Anxiety Stress Scale short form-Stress decreased significantly (P < .01, P = .009, P = .008, respectively). Three patients with congenital adrenal hyperplasia who reported positive nasopharyngeal swab tests revealed mild symptoms. Conclusion: The pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes. [ABSTRACT FROM AUTHOR]

Objective: Phosphomannomutase 2 deficiency (PMM2-CDG) is a disorder of protein N-glycosylation with a wide clinical spectrum. Hypoglycemia is rarely reported in PMM2-CDG. In this study, we evaluated cause, treatment options and outcomes in cases with hypoglycemia in the course of PMM2-CDG. Methods: Clinical records of patients followed with PMM2-CDG within the last two decades were reviewed. Medical data of patients with hypoglycemia were evaluated in more detail. Demographic and clinical findings, organ involvement and laboratory investigations at time of hypoglycemia were recorded. Time of first attack of hypoglycemia, cause, treatment modalities, duration of hypoglycemia (permanent/transient), and duration of treatment, as well as outcome were also recorded. Other published cases with PMM2-CDG and hypoglycemia are also reviewed in order to elucidate characteristics as well as pathophysiology of hypoglycemia. Results: Nine patients with PMM2-CDG were reviewed, and hypoglycemia was present in three cases. All three had hyperinsulinism as the cause of hypoglycemia. In the first two cases reported here, serum insulin level concurrent with hypoglycemic episodes was elevated, and glucose response was exaggerated during glucagon test, favoring hyperinsulinism. However, in the third case, the serum insulin level at time of hypoglycemia was not so high but hypoglycemia responded well to diazoxide. Hyperinsulinism was permanent in two of these three cases. No genotype-phenotype correlation was observed with respect to hyperinsulinism. Conclusion: The main cause of hypoglycemia in PMM2-CDG appears to be hyperinsulinism. Although insulin levels at the time of hypoglycemia may not be very high, hypoglycemia in patients with PMM2 responds well to diazoxide. [ABSTRACT FROM AUTHOR]

Objective: Oculoauriculovertebral spectrum (OAVS) is a genetically and clinically heterogeneous disorder that occurs due to a developmental field defect of the first and second pharyngeal arches. Even though recent whole exome sequencing studies (WES) have led to identification of several genes associated with this spectrum in a subset of individuals, complete pathogenesis of OAVS remains unsolved. In this study, molecular genetic etiology of OAVS was systematically investigated. Design/Setting/Patients: A cohort of 23 Turkish patients with OAVS, referred to Hacettepe University Hospital, Department of Pediatric Genetics from 2008 to 2018, was included in this study. Minimal diagnostic criteria for OAVS were considered as unilateral microtia or hemifacial microsomia with preauricular skin tag. The cohort was clinically reevaluated for craniofacial and extracranial findings. Molecular etiology was investigated using candidate gene sequencing following copy number variant (CNV) analysis. WES was also performed for 2 of the selected patients. Results: Patients in the study cohort presented similar demographic and phenotypic characteristics to previously described patients in the literature except for a higher frequency of bilaterality, cardiac findings, and intellectual disability/developmental delay. CNV analysis revealed a possible genetic etiology for 3 patients (13%). Additional WES in 1 of the 2 patients uncovered a novel heterozygous nonsense variant in Elongation factor Tu GTP-binding domain-containing 2 (EFTUD2) causing mandibulofacial dysostosis with microcephaly (MFDM), which clinically overlaps with OAVS. Conclusion: Detailed clinical evaluation for any patient with OAVS is recommended due to a high rate of accompanying systemic findings. We further expand the existing genetic heterogeneity of OAVS by identifying several CNVs and a phenotypically overlapping disorder, MFDM. [ABSTRACT FROM AUTHOR]

Hemophagocyticlymphohistiocytosis is a life-threatening condition of severe hyperinflammation that results from an uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. The immediate treatment strategies include immune suppressive therapy such as corticosteroid, etoposide and cyclosporin A. Herein, we present a 13-month-old infant who developed severe hypertrichosis after the administration of HLH-2004 treatment protocol. We discuss the various hypotheses regarding the causal relationship between cyclosporin A and hypertrichosis, emphasizing the importance of patient follow up.

Objective: Estrogen-secreting adrenocortical tumors (ACTs) are quite rare with feminizing adrenocortical tumors (FATs) accounting for 0.37-2% of all ACTs. The aim was to evaluate clinical and hormonal characteristics of FATS as well as treatment options and follow-up in the pediatric age group. Methods: Medical records of children with ACTs presenting to a single center in the last two decades were reviewed. Literature review within Pubmed revealed 34 pediatric patients (22 boys) with FAT among 192 articles. Results: Among the 25 children presenting with ACTs in the last two decades, two new pediatric cases of FAT were identified, one benign and the other malignant, in two genders with different clinical presentations. Literature review showed that FATs are extremely rare tumors that are most commonly seen in men and boys presenting with gynecomastia. FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. While boys present with contrasexual pseudopuberty signs, girls present with isosexual pseudopuberty. A high estrogen level strongly supports diagnosis, while elevations in other adrenal hormones may be seen. FATs are usually malignant in adults and prognosis is generally very poor. However, in children approximately half are benign although assessment of malignant potential depends on clinical behavior of the tumor. FATs are very unpredictable so even after surgery long-term follow-up is required. FATs presenting in childhood may have a better prognosis than adult presentation tumors as most FATs in children are followed without recurrence of tumor. Conclusion: FATs are more common in children ≤8 years of age, with a median age at diagnosis of six years. FATs in childhood may have a better prognosis than in adult males. [ABSTRACT FROM AUTHOR]

An obstetric ultrasound of a 38 years old woman with a dichorionic diamniotic twin pregnancy showed an increased nuchal translucency and absent nasal bone in one of the fetuses suggesting us an increased risk f or Down Sy ndrome (DS). This fetus was detected to hav e trisomy 21 (47, XX+21) by investigation of the amniocentesis material and was selectively undergone feticide process at 20 weeks of gestation. The other f etus (46, XX) was successf ully delivered at 36 weeks without any complications.

Background: Intellectual disability (ID), or developmental delay (DD) when the individual is yet under 5 years of age, is evident before 18 years of age and is characterised by significant limitations in both intellectual functioning and adaptive behaviour. ID/DD may be clinically classified as syndromic or non‐syndromic. Genomic copy number variations (CNVs) constitute a well‐established aetiological subgroup of ID/DD. Overall diagnostic yield of microarrays is estimated at 10–25% for ID/DD, especially higher when particular clinical features that render the condition syndromic accompany. Methods: In this study, we aimed to investigate the diagnostic yield of microarrays in the subgroup of individuals with non‐syndromic ID/DD (NSID/NSDD). A total of 302 NSID/NSDD individuals who have undergone microarray analysis between October 2013 and April 2020 were included. Accompanying clinical data, including head circumference, delayed developmental areas, seizures and behavioural problems were collected and analysed separately in NSID and NSDD subgroups. Results: The diagnostic yield of microarray analyses in NSID/NSDD was determined as 10.9% in NSID (10.7%) and in NSDD (11.1%). Presence of behavioural and epileptic problems did not contribute to the diagnostic yield. However, in the presence of macrocephaly, the contribution to diagnostic yield was statistically significant particularly in NSDD group. The most common pathogenic CNVs involved chromosomes 16, 15 and X. Lastly, we propose a Xq21.32q22.1 deletion as likely pathogenic in a child with isolated language delay and accompanying seizures. Conclusions: Particularly in neurodevelopmental diseases, microarrays are useful for establishing the diagnosis and detecting novel susceptibility regions. Future studies would accurately classify the herein presented variants of uncertain significance CNVs as pathogenic or benign. [ABSTRACT FROM AUTHOR]

Objective: Initial high-dose sodium levothyroxine (Na-LT4) (10-15 µg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels. Methods: Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups. Results: Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 µg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016). Conclusion: Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pretreatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week. [ABSTRACT FROM AUTHOR]

Background: Aetiological diagnosis in non‐syndromic intellectual disability (NSID) still poses a diagnostic challenge to clinicians. Methods: Screening is currently achieved by chromosomal microarrays followed by whole‐exome sequencing (WES). In search for the aetiological yield of WES in patients with NSID, 59 unrelated patients were studied. Results: Among the 59 patients, 44 (74.6%) were from consanguineous unions. Epilepsy was present in 11 (37.9%), behavioural problems in 12 (41.4%) and autistic features in 14 (48.3%). WES analysis resulted in molecular diagnosis in 29 patients (49.2%). Some of the genes were specific for nervous system functioning, like HERC1, TBC1D7, LINS, HECW2, DEAF1, HNMT, DLG3, NRXN1 and HUWE1. Others were ubiquitously expressed genes involved in fundamental cellular processes, like IARS, UBE3A, COQ4, TAF1, SETBP1, ARV1, ZC4H2, KAT6A, ASXL3, THOC6, HNRNPH2, TUBA8 and KIF1A. Twenty‐two (75.8%) were consanguineously married; however, only 12 (41.4%) of the detected genes caused autosomal recessive phenotypes. Conclusions: This cohort suggests that recessive genes probably represent an actually smaller subgroup of NSID, even among families with consanguinity. Although in societies with high consanguinity rates, considering the recessive inheritance first seems to be an advantageous strategy, de novo mutations in autosomal dominantly expressed genes represent the major aetiological group in patients with NSID, even among those patients from consanguineous families. [ABSTRACT FROM AUTHOR]

Colony stimulating factor 1 receptor (CSF1R, MIM# 164770) encodes a tyrosine‐kinase receptor playing an important role in development of osteoclasts and microglia. Heterozygous CSF1R variants have been known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, MIM# 221820), an adult‐onset leukoencephalopathy characterized by loss of motor functions and cognitive decline. Recently, a new phenotype characterized by brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) with biallelic CSF1R pathogenic variants in the etiology has been described. BANDDOS differs from HDLS by early‐onset neurodegenerative changes with additional structural brain abnormalities and skeletal findings resembling dysosteosclerosis (DOS). Described skeletal findings of the disease are highly variable ranging from absence of a skeletal phenotype and milder Pyle disease‐like to osteopetrosis and DOS. To date, only a few patients carrying biallelic CSF1R variants have been reported. In this clinical report, we describe three siblings with variable skeletal findings along with neurological symptoms ranging from mild to severe in whom exome sequencing revealed a novel homozygous splice site variant in canonical splice donor site of intron 21 adjacent to an exon, which encoding part of kinase domain of CSF1R along with a review of the literature. [ABSTRACT FROM AUTHOR]

Background. Central precocious puberty (CPP) is idiopathic in 90% of girls and 60% of boys, while some cases are caused by lesions of central nervous system (CNS), a condition often referred to as organic CPP. We aimed to analyze the etiology of organic CPP in a large cohort of girls and boys and determine gender-related differences. Methods. Medical files of 256 girls and 120 boys diagnosed and treated for CPP in a single center in the last two decades were reviewed. Patients were classified into four groups with respect to previous history and MRI findings: (1) previously established CNS pathology at the time of diagnosis, (2) novel CNS pathology previously asymptomatic, (3) incidentalomas considered to be unrelated to CPP, and (4) completely normal MRI. Group 1 and 2 were considered as organic CPP whereas group 3 and 4 were considered as idiopathic CPP. Results. Prevalence of CNS pathology was significantly higher in boys than girls (21.7% vs 6.2%). Previous CNS pathologies such as developmental anomaly of CNS, parenchymal injury, necrotic lesions and hydrocephalus were present in 3.5% of girls and 8.3% of boys. Prevalence of novel CNS pathology as determined by imaging among neurologically asymptomatic patients was 2.8% in girls and 14.5% in boys. The most common novel CNS pathologies in boys were hamartomas (5%) and suprasellar arachnoid cysts (3.3%); which were significantly lower in girls (0.8 and 0.8% respectively). Onset of organic CPP was before six years in girls, and seven years in boys. Conclusions. Organic CPP was 3.5 times more common in boys compared to girls. It is possible to detect an underlying CNS pathology in one out of every five boys with CPP. Frequency and distribution of organic etiology also differ between girls and boys, hypothalamic hamartomas and suprasellar arachnoid cysts being more common in boys than girls. The likelihood of novel intracranial pathology associated with CPP is quite low in girls with an onset after six years of age and in boys with an onset after seven years of age. [ABSTRACT FROM AUTHOR]

Objective: Aim of this study was to evaluate whether intravenous bolus administration of dexamethasone, a long-acting and potent glucorticoid, and methylprednisolone, a moderately acting and moderately potent glucocorticoid, causes adrenal insufficiency. Material and Methods: Forthy-six patients (24 girls, 22 boys) aged 2 months-18 years who were treated with intravenous dexamethasone or methylprednisolone for more than ten days for various reasons and referred to the department of pediatric endocrinology for discontinuation of steroids were included. Chronological age, duration of corticosteroid treatment (in days), mean hydrocortisone equivalent treatment dose (mg/m²/day), basal ACTH and cortisol levels, and peak cortisol response at low dose ACTH stimulation test were recorded. Morning serum basal cortisol levels of less than 3 µg/dl (85 nmol/L) were evaluated in favor of adrenal insufficiency due to corticosteroid use, and above 20 µg/dl was considered normal. Peak cortisol level ≥18 µg/dl (500 nmol/L) was considered normal in low-dose ACTH stimulation test. Results: Mean age of the patients was 7.9±5.8 years (range 2 months-18 years), mean duration of corticosteroid use was 26.2±11.8 days (range 12-75) days, mean daily dose number was 2.2±1.2 (range 1-4), mean hydrocortisone equivalent corticosteroid dose was 235.6±114.6 (range 86-428) mg/m²/day. Mean basal cortisol and ACTH levels were 9.9±4.0 (range 4.2-16.8) pg/dl, 30.4±18.6 (range 8.6-72.5) pg/ml, respectively. Peak cortisol response at low dose ACTH stimulation test was ≥18 µg/dl in all cases. Conclusion: In this study, intravenous bolus administration of glucocorticoids did not cause adrenal suppression in any case. Despite the intravenous administration of potent glucocorticoids such as dexamethasone and methylprednisolone over a long period of 26 days in supraphysiological doses, adrenal suppression did not develop in any of the cases, indicating that the administration route of the drug is as important as the duration and the dose of treatment. Intravenous bolus administration of glucorticoids may be less risky for adrenal suppression.Further studies involving more cases are needed. [ABSTRACT FROM AUTHOR]

Background and objectives. Congenital adrenal hyperplasia (CAH) is characterized by androgen excess which should be treated with life-long glucocorticoid therapy, thus can affect bone mineralization. We aimed to evaluate the bone mineral density (BMD) and determine the factors affecting bone mineralization in patients with CAH. Method. This prospective case-control study was conducted in children, adolescents and young adults with classical 21-hydroxylase CAH, and age-, sex-, and pubertal stage matched healthy controls. Lumbar1-4 BMD was determined by dual-energy X-ray absorptiometry. BMD z-score was calculated using national standards with respect to height age and was referred as "low BMD" if z-score < -1 SD. Univariate analyses were performed between low BMD and normal BMD groups, and multivariate logistic regression analysis was performed to assess the independent predictors of low BMD. Correlations of Body Mass Index (BMI)-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses with BMD z-score were evaluated with Spearman analyses. Results. Each group included 37 cases. BMD z-score of patients with CAH [0.47 (-0.04 -1.56)] was higher than control group [-0.43 (-0.82 -0.05)]; p= < 0.001. Number of patients with low BMD was similar in both groups; [CAH: 6(16.2%), control: 5(13.5%); p= 0.744]. BMI- z-score was higher in patients with CAH when compared to control group; p= < 0.001. BMI z-score was lower in low BMD group as comparison to normal BMD group; p= 0.041. Each 1.0 decrease in BMI z-score, risk of having low BMD was found to increase by 1.79 (%95 CI: 1.03- 3.12, p= 0.040). BMI-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses were not found to be correlated with BMD z-score. Conclusion. Long-term glucocorticoid therapy did not have negative effect on BMD of patients with CAH. Higher BMI z-score in patients with CAH may have a positive effect on preserving bone health. Precautions should be taken for increased risk of obesity. [ABSTRACT FROM AUTHOR]

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Objective: Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose. Methods: Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate. Results: Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001). Conclusion: Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis. [ABSTRACT FROM AUTHOR]