Pitfalls of diagnosing pituitary hypoplasia in the patients with short stature.

PURPOSE: Height age (HA) and bone age (BA) delay is well known in the patients with short stature. Therefore assessing pituitary hypoplasia based on chronological age (CA) might cause overdiagnosis of pituitary hypoplasia. We aimed to investigate the diagnostic and prognostic value of the PH and PV based on CA, HA, or BA in the patients with GHD. METHODS: Fifty-seven patients with severe and 40 patients with partial GHD and 39 patients with ISS assigned to the study. For defining the most accurate diagnosis of pituitary hypoplasia, PH and PV were evaluated based on CA, BA and HA. The relationship of each method with clinical features was examined. RESULTS: The mean PV was significantly larger in patients with ISS compared to the GH-deficient patients. PV was more correlated with clinical features including height SDS, stimulated GH concentration, IGF-1 and IGFBP-3 SDS, height velocity before and after rGH therapy. We found BA-based PV could discriminate GHD from ISS (Sensitivity: 17%, specificity: 98%, positive predictive value: 94%, negative predictive value: 39%), compared to the other methods based on PH or PV respect to CA and HA. 3% of patients with ISS, 17% of patients with GHD had pituitary hypoplasia based on PV-BA. CONCLUSION: PV based on BA, has the most accurate diagnostic value for defining pituitary hypoplasia. But it should be kept in mind that there might be still misdiagnosed patients by this method. PV is also a significant predictor for the rGH response.

Current Diagnostic Approaches in the Genetic Diagnosis of Disorders of Sex Development.

Disorders of sex development (DSD) are a clinically and genetically highly heterogeneous group of congenital disorders. The most accurate and rapid diagnosis may be possible with a complementary multidisciplinary diagnostic approach, including comprehensive clinical, hormonal, and genetic investigations. Rapid and accurate diagnosis of DSD requires urgency in terms of gender selection and management of the case. Despite the genetic tests performed in current daily practice, the genetic cause is still not elucidated in a significant proportion of cases. Karyotype analysis can be used as a standard for sex chromosome identification. In addition, quantitative fluorescent polymerase chain reaction (QF-PCR) or fluorescence in situ hybridization (FISH) analysis can be used for faster and more cost-effective detection of the sex chromosome and SRY gene. Multiplex ligation-dependent probe amplification (MLPA), single-gene sequence analysis, next-generation sequence analysis (NGSA), targeted NGSA, whole-exome sequencing (WES), and whole-genome sequencing (WGS) analyses can be performed according to preliminary diagnoses. Microarray analysis (array comparative genomic hybridization (aCGH) and single nucleotide polymorphism array (SNPa)) should be performed in cases with syndromic findings and if no pathology is detected with other tests. In DSD cases, the use of optical genome mapping and techniques, which will probably be in daily practice in near future, may be considered. In conclusion, the clinical and genetic diagnosis of DSD is difficult, and molecular genetic diagnosis is often not available. This has psychosocial and health implications for patients and their families. New genetic techniques, especially those targeting the whole genome, may provide a better understanding of DSD through the identification of little-known genetic causes. This review focuses on conventional genetic and next-generation genetic techniques used in the genetic diagnosis of DSD, as well as possible genetic diagnostic techniques and approaches that may be used in routine practice in near future.

Continuous Glucose Monitoring Systems and the Efficacy of Acarbose Treatment in Cystic Fibrosis-related Dysglycemia.

Early detection of glycemic dysregulation and optimization of glycemic control at cystic fibrosis related diabetes (CFRD) is associated with improved pulmonary function and decreased mortality. The standard 2-hour oral glucose tolerance test (OGTT) is the current routine screening test for CFRD. However, hyperglycemia can be detected by continuous glucose monitoring systems (CGMS) in patients with normal OGTT evaluation. High-dose acarbose is an important alternative, in the treatment of glycemic dysregulation especially accompanied by hypoglycemia. A 7-year-old boy with cystic fibrosis (CF) presented with hyperglycemia. Hypoglycemia (29 mg/dL) and hyperglycemia (400 mg/dL) were demonstrated by OGTT and intermittent CGM (iCGMS). Thickener was added to nutritional solutions and acarbose was initiated as 3x12.5 mg /dose and increased to 6x25 mg without any side effects. On the 20th day of treatment, glycemic dysregulation was resolved. In the early detection of CFRD, screening with OGTT after the age of 10 is insufficient; therefore, routine use of continous or intermittent glucose monitoring systems should be considered. In addition, in CFRDs with severe hypoglycemia, acarbose is an important alternative in the high and increased dose range.

Isolated Hyperthyrotropinemia Adversely Influences Lipid Metabolism in Children and Adolescents with Obesity.

OBJECTIVE: The aim of this study is to look at the relationship between hyperthyrotropinemia and anthropometric measurements as well as cardiometabolic risk factors in obese children and adolescents. MATERIALS AND METHODS: A total of 100 patients with isolated hyperthyrotropinemia and 124 patients with normal thyroid functions, between 10 and 18 years of age, were included in the study. Anthropometric and blood pressure measurements and biochemical parameters were recorded. Non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, and triglyceride/high-density lipoprotein cholesterol ratios were calculated. RESULTS: The subjects' mean age was 12.6 ± 1.9 years and their mean body mass index was 29.8 ± 4 kg/m2. The isolated hyperthyrotropinemia group had considerably greater levels of triglyceride, non-high-density lipoprotein cholesterol, and the triglyceride/high-density lipoprotein cholesterol ratio. Higher prevalences of hypertriglyceridemia and increased triglyceride/high-density lipoprotein cholesterol ratio were found in the group with isolated hyperthyrotropinemia. Thyroid-stimulating hormone had a statistically significant positive relationship with triglyceride, non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride/high-density lipoprotein cholesterol ratio, as well as an inverse relationship with high-density lipoprotein cholesterol. Thyroid-stimulating hormone was positively correlated with triglyceride and triglyceride/high-density lipoprotein cholesterol ratio in both females and males; however, only in females, thyroid-stimulating hormone was positively correlated with non-high-density lipoprotein cholesterol and total cholesterol/highdensity lipoprotein cholesterol ratio. The triglyceride/high-density lipoprotein cholesterol ratio, as well as the rates of hypertriglyceridemia were higher in children with isolated hyperthyrotropinemia in the female subgroup. Male children with isolated hyperthyrotropinemia had significantly higher triglyceride levels in comparison with males with normal thyroid-stimulating hormone. CONCLUSION: The present study suggested that isolated hyperthyrotropinemia is associated with the deterioration of lipid metabolism, especially in females. Since dyslipidemia is accepted as a cardiovascular disease risk factor, isolated hyperthyrotropinemia might negatively influence cardiovascular functions in obese children and adolescents.

Reliability and Validity of the Turkish Version of Impact of Weight on Quality of Life for Kids.

OBJECTIVE: The Impact of Weight on Quality of Life-Kids is a self-reported weight-related quality of life measure that has been validated for children and adolescents aged between 11 and 19. Impact of Weight on Quality of Life-Kids does not have a Turkish version. The aim of this study was to explore the reliability and validity of the Impact of Weight on Quality of Life-Kids in Turkish. MATERIALS AND METHODS: The Impact of Weight on Quality of Life-Kids was translated into Turkish using Mapi Research Institute's suggested international translation technique. The psychometric evaluation included test-retest reliability, internal consistency, discriminant validity, concurrent validity, exploratory factor analysis, and confirmatory factor analysis. RESULTS: For the total score, the internal consistency of the scale (Cronbach's alpha coefficient) was 0.93. The item-total score correlation coefficients ranged from 0.178 to 0.785. The testretest coefficients were found to be 0.94 for the total score and the subscales ranged from 0.66 to 0.89 after 2 weeks. Discriminant validity analysis demonstrated that the instrument differentiated well between the obese and non-obese samples. Five variables were discovered via factor analysis that explained 66.9% of the total variation. The chi-square/degree of freedom ratio value was 3.535, the comparative fit index value was 0.834, and the value of root mean square error of approximation was 0.10, as determined by confirmatory factor analysis. CONCLUSION: Our results demonstrated the adequate reliability and validity of the Impact of Weight on Quality of Life-Kids, suggesting that this scale is a useful tool for screening Turkish children and adolescents for weight-related quality of life.

Urinary NGAL is a Potential Biomarker for Early Renal Injury in Insulin Resistant Obese Non-diabetic Children

Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is one of the new biomarkers for detecting acute renal injury. There are studies showing the relationship between NGAL and renal injury in obese children. The aim of this study was to investigate whether urinary levels of NGAL, kidney injury molecule-1, and serum cystatin C are increased in insulin resistance (IR) patients before the development of diabetes. Methods: Cross-sectional, case-controlled study that included non-diabetic obese children and adolescent patients with IR and a non-diabetic obese control group with no IR, who attended a tertiary center pediatric endocrinology outpatient clinic between 2016-2018. Those with diabetes mellitus and/or known renal disease were excluded. NGAL and creatinine (Cr) levels were evaluated in the morning spot urine from all participants. Serum renal function was evaluated. Results: Thirty-six control and 63 IR patients were included in the study, of whom 68 (68.7%) were girls. The mean age of all participants was 13.12±2.64 years and no statistically significant difference was found between the two groups in terms of age or gender distribution. Median (range) spot urinary NGAL (u-NGAL) values in the IR group were significantly higher at 26.35 (7.01-108.7) ng/mL than in the control group at 19.5 (3.45-88.14) ng/mL (p=0.018). NGAL/Cr ratio was also significantly higher in the IR group compared to the control group (p=0.018). Conclusion: Obese pediatric patients with IR were shown to have elevated levels of u-NGAL, a marker of renal injury. u-NGAL examination may show early renal injury before development of diabetes.

Evaluation of lower urinary tract symptoms in children with Down syndrome: A prospective, case-controlled cohort study.

AIMS: In children with Down syndrome (DS) which causes cognitive impairment and intellectual disability (ID), dysfunctional voiding is proposed to be more common than in the normal population. In this study, we aimed to compare the voiding symptoms of DS children with a control group by validated questionnaires. METHODS: Thirty-seven DS children without any previous urological complaints and 59 non-DS healthy children as control group was included in the study. Overactive bladder symptoms and dysfunctional voiding were evaluated with validated Overactive Bladder Questionnaire (OAB-V8) and Dysfunctional Voiding Symptom Score (DVSS) questionnaire, respectively. Data were arranged, descriptive and comparative statistical analysis were performed. RESULTS: Demographic data of the two groups were similar except age of completing toilet training being higher in DS group. Total OAB-V8 and DVSS scores were significantly higher in the DS group. The mean scores of questions regarding voiding frequency, urgency and urgency incontinence in OAB-V8 were significantly higher in the DS group. The mean daytime incontinence, urgency, urgency incontinence, and quality of life scores in the DVSS were also significantly higher in the DS group. CONCLUSIONS: DS children have more frequent dysfunctional voiding than the normal population. ID of these children may prevent the expression of these symptoms. Awareness and early detection of these symptoms are crucial to prevent devastating complications such as renal failure. Therefore, validated questionnaires are simple, useful, and noninvasive methods.

Mental health of both child and parents plays a larger role in the health-related quality of life of obese and overweight children.

Aims A decrease in health-related quality of life (HRQOL) measures among obese (OB) and overweight (OW) children has been shown in several studies, but knowledge about the variables affecting HRQOL impairments is missing. The aim of this study was to evaluate the relationship between HRQOL and sociodemographic characteristics, anthropometric measurements, metabolic parameters, mental symptoms and parental attitudes in a sample of OB/OW children. Methods Eighty-six OB/OW children, aged between 9 and 17 years, participated in the study. We performed sociodemographic questioning, anthropometric examinations and laboratory evaluations of the participants. HRQOL was assessed using the Pediatric Quality-of-Life Inventory (PedsQL), and levels of anxiety and depressive symptoms were measured using the Screen for Child Anxiety-Related Disorders (SCARED) questionnaire and the Children's Depression Inventory (CDI), respectively. Parental attitudes were assessed with the Parental Attitude Research Instrument (PARI) questionnaire. Results A statistically significant relationship was found between total scores of CDI and SCARED answered by children and the total and subscale scores of PedsQL. Scores of total quality of life subscale, physical functionality and emotional functionality subscales were significantly lower in children with a family history of mental illness. No relationship was found between PedsQL subscales, anthropometric and metabolic parameters. Conclusions Emotional problems and parental psychological distress are important factors in models of HRQOL in the OB/OW pediatric population.

Associations Between Serum Uric Acid Concentrations and Cardiometabolic Risk and Renal Injury in Obese and Overweight Children

Objective: The aim of this study was to assess the association between serum uric acid concentration (SUAC) and the parameters of the metabolic syndrome (MetS) and insulin resistance (IR). The secondary aim was to evaluate whether hyperuricemia is associated with renal injury and cardiovascular risk in obese (OB) and overweight (OW) children. Methods: The subjects of this study consisted of OB/OW children and adolescents (ages: 8-18 years). Sex and age specific serum uric acid (SUA) olarak degistirilecek percentiles were used and a SUA >75th percentile was accepted as hyperuricemia. Anthropometric data, blood pressure (BP) measurements and biochemical parameters, including fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, triglycerides (TG), aspartate aminotransferase, alanine aminotransferase, homeostatic model assessments of IR (HOMA-IR) and SUAC were recorded. Oral glucose tolerance tests (OGTT) were performed in all patients. MetS was defined according to the International Diabetes Federation criteria. Total cholesterol/HDL-c ratio >4 and TG/HDL-c ratio >2.2 were used as the atherogenic index (AI) indicating cardiovascular risk. Urinary albumin excretion in a 24-hour and also in a first-morning urine sample were measured. Renal injury was assessed by microalbuminuria according to the National Kidney Foundation criteria. Results: There were 128 participants; 52 (40%) had elevated (SUA >75th percentile) and 76 had (60%) normal SUAC. The mean±SD age was 13.1±2.6 years and 87 (67.4%) were female. The mean±SD weight was 73±18.97 kg and mean±SD height was 155.4±12.11 cm. There was no statistical difference between the groups with and without hyperuricemia in terms of age, sex, puberty stage and degree of obesity. Increased SUAC were significantly associated with higher waist-to-hip ratio (WHR), fasting insulin levels and insulin at 30 and 60 minutes during OGTT, HOMA-IR, lower HDL-c and presence of hypertriglyceridemia as well as with decreased HDL-c, increased AI, presence of IR and MetS. BP and microalbuminuria were not associated with SUAC. SUAC showed significant positive correlations with waist circumference, WHR, post-challenge glucose level at 60 minutes, with fasting insulin, post-challenge insulin levels at 30, 60, 90 and 120 minutes and also with HOMA-IR, total cholesterol/HDL-c ratio, TG/HDL-c ratio and a number of other criteria related to MetS. Also, an inverse correlation with HDL-c was noted. Conclusion: In OB/OW children frequency of MetS, IR and dislipidemia increases with increased SUAC, a finding independent of age, puberty, gender and body mass index. Patients meeting all of the MetS criteria had the highest SUAC. These results demonstrate that the association between UA and metabolic and cardiovascular risk factors can be detected early in childhood. Thus, we recommend monitoring SUAC in OB children and we believe that prevention of SUAC elevation in early life has a potential protective effect on metabolic impairment and subsequent comorbidities.

Insulin Resistance as Related to Psychiatric Disorders in Obese Children

Objective: The current study aimed to investigate psychiatric consequences of obesity and the relationship between componenets of the metabolic syndrome and psychiatric disorders in children. Our second aim was to elucidate which of the anthropometric parameters or metabolic components were most strongly associated with psychiatric disorders. Methods: The study included 88 obese and overweight children with a body mass index (BMI) greater than 85th percentile. The patients were evaluated for psychiatric disorders by a single child and adolescent psychiatrist. Forty patients diagnosed with psychiatric disorders and 48 patients with normal psychiatric evaluation were compared in terms of anthropometric and metabolic parameters. BMI, BMI-standard deviation score and BMI percentile, waist circumference, waist to hip ratio, blood pressure and pubertal stage of all patients were recorded. Fasting serum glucose, insulin, lipid profile and homeostatic model assessments of insulin resistance (HOMA-IR) were measured to evaluate the metabolic parameters. Serum and 24 hour urine cortisol levels were measured. Results: HOMA-IR in the group with psychiatric disorders was found to be significantly higher than in the group without psychiatric disorders (6.59±3.36 vs 5.21±2.67; p=0.035). Other anthropometric measurements and metabolic parameters were not significantly different between the two groups. Conclusion: An understanding of the relationships between obesity related medical comorbidities and psychiatric pathologies is important to encourage patients and their families to make successful healthy lifestyle changes and for weight management in terms of appropriate treatment.