The psychosocial outcomes of advanced hybrid closed-loop system in children and adolescents with type 1 diabetes.

The study was carried out to determine the psychosocial outcomes of advanced hybrid closed-loop (AHCL) systems in children and adolescents with type 1 diabetes (T1D). Single-center and cohort study with a duration 6 months consisted of 60 children and adolescents with T1D. Standard clinical procedures, including both glycemic indicators, e.g., sensor-measured time within the 70-180 mg/dL range and glycated hemoglobin (HbA1c) levels, and psychosocial metrics were used for data collection. The psychosocial metrics included the Pediatric Quality of Life Inventory (PedsQL) 3.0 Diabetes Module for both children (8-12 years) and parents; the Quality of Life for Youth scale for adolescents (13-18 years); the Strengths and Difficulties Questionnaire (SDQ); the Hypoglycemia Fear Survey for Children (HFS-C); the Revised Child Anxiety and Depression Scale (R-CADS); and AHCLS-specific DTSEQ satisfaction and expectation survey. These metrics were evaluated at the baseline and after 6 months of AHCL use. Of the 60 children and adolescents with T1D for whom the AHCL system was utilized, 41 of them, 23 female and 18 male, completed the surveys. The mean age of the 41 children and adolescents was 12.5 ± 3.2 (min. 6.7, max. 18) years. The time spent within the target glycemic range, i.e., time-in-range (TIR), improved from 76.9 ± 9% at the baseline to 80.4 ± 5% after 6 months of AHCL system use (p = 0.03). Additionally, HbA1c levels reduced from 7.1% ± 0.7% at the baseline to 6.8% ± 0.8% after 6 months of AHCL system use (p = 0.03). The most notable decline in HbA1c was observed in participants with higher baseline HbA1c levels. All patients' HFS-C and AHCL system-specific DTSEQ satisfaction and expectation survey scores were within the normal range at the baseline and remained unchanged during the follow-up period. No significant difference was found in the R-CADS scores of children and adolescents between baseline and after 6 months of AHCL system use. However, there was a significant decrease in the R-CADS scores of the parents. Patients' PedsQL scores were high both at the baseline and after 6 months. The SDQ scores were high at baseline, and there was no significant improvement at the end of 6 months.  Conclusion: This is the first study to investigate in detail the psychosocial outcomes of AHCL system use in T1D patients and their parents. Although state-of-the-art technologies such as AHCL provide patients with more flexibility in their daily lives and information about glucose fluctuations, the AHCL resulted in a TIR above the recommended target range without a change in QOL, HFS-C, SDQ, and R-CADS scores. The scores obtained from the R-CADS conducted by the parents of the children indicated that the use of pumps caused a psychological improvement in the long term, with a significant decrease in the R-CADS scores of the children and adolescents with T1D. What is Known: • Previous studies focused on clinical outcomes of AHCL systems in pediatric T1D patients, showing glycemic control improvements. • Limited attention given to psychosocial outcomes of AHCL systems in children and adolescents with T1D. • Crucial psychosocial factors like quality of life, emotional well-being, and fear of hypoglycemia underexplored in AHCL system context. What is New: • First study to comprehensively examine psychosocial outcomes of AHCL systems in pediatric T1D patients. • Study's robust methodology sets new standard for diabetes technology research and its impact on qualiy of life.

Local complications of insulin administration sites and effect on diabetes management.

BACKGROUND: Administration of insulin may be associated with substantial cutaneous adverse effects, such as lipoatrophy and lipohypertrophy (LH), which can cause glycemic excursions above and below the target levels for blood glucose. Our aim was to evaluate the effect on compliance with the use of insulin administration site, dermatological complications and diabetes management in children with type 1 diabetes (T1D). METHODS: Patients aged 0 - 21 years who were followed up with the diagnosis of T1D for at least one year were included. A 14-question survey including demographic characteristics and a subjective opinion of skin-related complications of insulin administration was given. Data were obtained from the medical records to evaluate the effect of dermatological complications on diabetes management. This study was checked with the STROBE checklist. RESULTS: Two hundred and fifty-four patients were included and 53% of these were female. The mean age was 14.9 ± 4.7 years and the duration of T1D was 7.3 ± 4.1 years. The mean HbA1c level was 8 ± 1.4% and the mean total insulin dose was 0.84 ± 0.25 units/kg/day. More than half of the individuals (57%) were receiving multiple daily injections (MDI) and 43% were on insulin pump therapy (IPT). Of the participants, 11.8% reported LH, 7.5% wound, 21.7% allergy, 55.5% bleeding, 41.3% bruising and 47.2% pain. LH rates varied significantly by regimen, 17.1% in MDI and 4.6% with IPT (p = .001). Those with LH were using higher median doses of insulin (0.97 U/kg/day) than those who did not (0.78 U/kg/day; p = .016). LH was reported more frequently (18.3%) in patients with frequent hypoglycemia (p = .007). Positive correlation between BMI-SDS and LH in patients aged <18 years was found (p = .043). LH rates by site were: right arm 20.8%, left arm 26.4%, right abdomen 26.4%, left abdomen 22.6% and 1% in the right and left leg. CONCLUSIONS: Local complications of insulin therapy are common in young patients with T1D. The complication with the most impact on metabolic control was LH, present in nearly 12% of patients. Users of IPT have a significantly lower risk of LH. The results emphasise the importance of individualised education for young T1D patients and their families about injection site preference and rotation techniques. RELEVANCE TO CLINICAL PRACTICE: The diabetes team should check the insulin administration sites of children with type 1 diabetes at each visit and provide repeated education about the dermatological complications of insulin.

A rare cause of syndromic short stature: 3M syndrome in three families.

3M syndrome is a rare autosomal recessive genetic disorder characterized by severe growth retardation, dysmorphic facial features, skeletal dysplasia, and normal intelligence. Variants in CUL7, OBSL1, and CCDC8 genes have been reported to be responsible for this syndrome. In this study, the clinical and molecular findings of four 3M syndrome cases from three families are presented. All cases had growth retardation, relative macrocephaly, and typical dysmorphic facial features. Their neurological developments were normal. Sequencing of CUL7, OBSL1, and CCDC8 genes revealed two different novel homozygous variants in CUL7 in Families 1 and 3 and a previously reported homozygous pathogenic variant in OBSL1 in Family 2. In conclusion, a comprehensive dysmorphological evaluation should be obtained in individuals presenting with short stature and in such individuals with typical facial and skeletal findings, 3M syndrome should be considered. Our report expands the genotype of 3M syndrome and emphasizes the importance of thorough physical and dysmorphological examination.

Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics.

Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m2. Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing.Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years. What is known • The frequency of MC4R mutations in obese patients was approximately 0-6.3%. What is new • In obese Turkish pediatric population, unlike other European countries, MC4R gene variants are quite common as we found a variant rate of 8.6% • We believe it is necessary to screen the variants in MC4R gene in patients with severe childhood-onset obesity and who had early-onset obesity in at least one of their first-degree relatives in Turkish population.

Growth evaluation in children with vesicoureteral reflux.

BACKGROUND: Vesicoureteral reflux and urinary tract infection predispose children to retardation of growth, hypertension, renal scarring and renal failure. The aim of this study was to evaluate growth pattern in children with vesicoureteral reflux before and after medical/surgical treatment. METHODS: This study was a retrospective cross-sectional study. The study population included 97 children aged 0.5 to 17 years (8.8±5.5). Body weight, height and bone age of the children were measured. Weight Z score and height Z score were calculated during first visits and after medical and/or surgical treatment. Distribution, mean and standard deviation score were evaluated for the descriptive data. T-test and Mann-Whitney U test and Wilcoxon test were used for statistical analysis. RESULTS: Sixty-five percent of 97 children enrolled in this study were girls. About 48.5% of the children had unilateral and mild reflux, while 16.5% had bilateral and severe reflux. The bone age was 8.6 years. Differentiation with chronological age and bone age were not significant (P=0.294). At admission, 54.6% and 50.5% of children had negative Weight Z score and height Z score, respectively. After medical and surgical treatment, Weight Z score and height Z score were increased, however, only the increase in Weight Z score was significant (P=0.039, P=0.031, respectively). A significant reduction in bone age was found in children with renal scars compared to those without renal scars (P=0.048). CONCLUSIONS: High-grade vesicoureteral reflux had a negative impact on indices of growth in children. Medical and/or surgical treatment had positive effect on weight gain.

Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome.

To evaluate the anthropometric features of girls with Turner syndrome (TS) at birth and presentation and the effect of karyotype on these parameters. Data were collected from 842 patients with TS from 35 different centers, who were followed-up between 1984 and 2014 and whose diagnosis age ranged from birth to 18 years. Of the 842 patients, 122 girls who received growth hormone, estrogen or oxandrolone were excluded, and 720 girls were included in the study. In this cohort, the frequency of small for gestational age (SGA) birth was 33%. The frequency of SGA birth was 4.2% (2/48) in preterm and 36% (174/483) in term neonates (P < 0.001). The mean birth length was 1.3 cm shorter and mean birth weight was 0.36 kg lower than that of the normal population. The mean age at diagnosis was 10.1 ± 4.4 years. Mean height, weight and body mass index standard deviation scores at presentation were -3.1 ± 1.7, -1.4 ± 1.5, and 0.4 ± 1.7, respectively. Patients with isochromosome Xq were significantly heavier than those with other karyotype groups (P = 0.007). Age at presentation was negatively correlated and mid-parental height was positively correlated with height at presentation. Mid-parental height and age at presentation were the only parameters that were associated with height of children with TS. The frequency of SGA birth was found higher in preterm than term neonates but the mechanism could not be clarified. We found no effect of karyotype on height of girls with TS, whereas weight was greater in 46,X,i(Xq) and 45,X/46,X,i(Xq) karyotype groups.

Difficulties experienced by caregivers of patients diagnosed with osteogenesisimperfecta (OI): example of a hospital.

OBJECTIVE: To identify the difficulties experienced by medical caregivers of inpatients diagnosed with osteogenesisimperfecta. METHODS: The descriptive, cross-sectional study was conducted at a university hospital in western Turkey from April to May, 2012, and comprised relatives providing care to patients who were diagnosed with osteogenesisimperfecta and were being treated in the paediatric endocrinology unit. Data was collected via face-to-face interviews with patient relatives. The 35-itemquestionnaire had 16 open-ended and 19 close-ended questions. RESULTS: The mean age of the 46 caregivers was 35.52±6.65 years, and 43(93.5%) of them were mothers. All of them said they felt anxious (100%), while 44(95.7%) felt sad/sorrow, 41(89.1%) puzzled, 40(87.0%) nervous, 40(87.0%) frightened, 39(84.8%) disappointed, 29(63%) shocked, and 28(60.9%) depressed when they first heard the diagnosis. Overall, 26(56.5%) experienced physical, 45(97.8%) psychological, 45(97.8%) social, and 35(76.1%) economic changes and difficulties, while 24(52.1%) had no social support. Of all the patient relatives, 38(82.6%) were unable to obtain adequate information about the disorder from the healthcare team. CONCLUSIONS: Caregivers of patients diagnosed with osteogenesisimperfecta experienced psychological and social difficulties..

Adherence to growth hormone therapy: results of a multicenter study.

OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify the influencing factors and outcomes in children. METHODS: A total of 217 GH-naïve patients in 6 pediatric endocrinology clinics were enrolled in the study. Structured questionnaires were filled out and patients were evaluated at the initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized into 4 adherence segments based on percentage of doses omitted at each evaluation period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study period (P = .006). Patients who showed excellent and good adherence to therapy had better growth velocity and growth velocity standard deviation scores (SDSs) (P = .014 and P = .015, respectively). A negative correlation between growth velocity SDS and number of missed injections was also observed (r = -.412; P = .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1) SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were significantly higher in patients who showed excellent and good adherence to therapy (P = .01). Adherence was better in boys than in girls (P = .035), but adherence rates were not associated with age, cause of GH treatment, socioeconomic status, person who administered the injections, type of injection device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our group of patients and was one of the factors underlying suboptimal growth during therapy. Before considering other problems that can affect growth, clinicians should confirm good adherence to therapy.

Effectiveness of whole exome sequencing analyses in the molecular diagnosis of osteogenesis imperfecta.

OBJECTIVES: Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and to determine the relationship between genotype and phenotype in OI patients with whole exome sequencing (WES). METHODS: Multiplex-Ligation dependent Probe Amplification (MLPA) analysis of COL1A1 and COL1A2 and WES were performed on cases between the ages of 0 and 18 whose genetic etiology could not be determined before using a targeted next-generation sequencing panel, including 13 genes (COL1A1, COL1A2, IFITM5, SERPINF1, CRTAP, P3H1, PPIB, SERPINH1, FKBP10, SP7, BMP1, MBTPS2, PLOD2) responsible for OI. RESULTS: Twelve patients (female/male: 4/8) from 10 different families were included in the study. In 6 (50 %) families, consanguineous marriage was noted. The clinical typing based on Sillence classification; 3 (25 %) patients were considered to be type I, 7 (58.3 %) type III, and 2 (16.7 %) type IV. Deletion/duplication wasn't detected in the COL1A1 and COL1A2 genes in the MLPA analysis of the patients. Twelve patients were molecularly analyzed by WES, and in 6 (50 %) of them, a disease-causing variant in three different genes (FKBP10, P3H1, and WNT1) was identified. Two (33.3 %) detected variants in all genes have not been previously reported in the literature and were considered deleterious based on prediction tools. In 6 cases, no variants were detected in disease-causing genes. CONCLUSIONS: This study demonstrates rare OI types' clinical and molecular features; genetic etiology was determined in 6 (50 %) 12 patients with the WES analysis. In addition, two variants in OI genes have been identified, contributing to the literature.

Does minimed 780GTM insulin pump system affect energy and nutrient intake?: long-term follow-up study.

OBJECTIVE: We evaluate the energy and nutrient intake of children, adolescents, and young adults with type 1 diabetes (T1D) who started to use automated insulin delivery (AID) systems before the transition and during follow-up for 6 months in a real-world setting. RESEARCH DESIGN AND METHODS: Twenty-nine people with T1D (PwD) who started to use MiniMed 780GTM participated in the study. Participants' 3-day food diaries and glycemic outcomes were analyzed at baseline and after (the 3rd and 6th month) switching to an advanced hybrid closed-loop system (a-HCL). RESULTS: Mean carbohydrate, protein, and fat intake (energy %) at baseline were 49.1 ± 4.5, 17.8 ± 2.3, and 33.0 ± 3.9, respectively, and there were no statistically significant differences during the follow-up period. However, low fiber (<14 g/1000 kcal) and high saturated fat (>10 energy %) intake in PwD, both baseline and follow-up period. The median auto-correction bolus ratio was 14.0 (9.5)% at auto mode after 14 days, 18.0 (11.0)% at the 3rd month, and 19.0 (7.5)% at the 6th month (p < 0.05). A negative correlation was present between auto-correction boluses with TIR in both the 3rd (r:-0.747, p < 0.01) and 6th month (r:-0.395, p < 0.05). A negative correlation was present between auto-correction boluses with TIR in both the 3rd (r:-0.747, p < 0.01) and 6th month (r:-0.395, p < 0.05). CONCLUSIONS: a-HCLS systems offer better glycemic control. Using the Minimed 780 GTM insulin pump system didn't change the energy and nutrient intake of PwD. This real-world follow-up study suggests that children, adolescents, and young adults with T1D consume saturated fat above and fiber intake lower than recommendations independent of the use of a-HCLS. CLINICAL TRIALS REGISTRATION NUMBER: NCT05666596.

Molecular Genetic Diagnosis with Targeted Next Generation Sequencing in a Cohort of Turkish Osteogenesis Imperfecta Patients and Their Genotype-phenotype Correlation.

Introduction: Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients with targeted next-generation sequencing (NGS). Method: In patients with OI, a targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform. Results: Fifty-six patients (female/male: 25/31) from 46 different families were enrolled in the study. Consanguinity between parents was noted in 15 (32.6%) families. Clinically according to Sillence classification; 18(33.1%) patients were considered to type I, 1(1.7%) type II, 26(46.4%) type III and 11(19.6%) type IV. Median body weight was -1.1 (-6.8, - 2.5) SDS, and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity was detected in 30 (53.5%) of the patients, while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) patients had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 genes were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes (FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected in all investigated genes were not previously reported in the literature and were classified to be pathogenic according to ACMG guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in a total of 13 OI genes included in the panel. Conclusion: Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. In addition, 9 new variants were assessed in known OI genes which is a significant contribution to the literature.

Through the eyes of the parents: a transdiagnostic psychiatric perspective for children with differences of sexual development.

PURPOSE: Existing literature lacks data on a subgroup exhibiting psychiatric symptoms below the DSM-5 diagnostic threshold within DSD cases. Our study aims to assess parental knowledge, attitudes toward DSD, and parental perceptions of emotional and behavioral states through a transdiagnostic perspective. METHODS: The study was conducted with a total of 35 parents of children with DSD. Two groups were established via k-means clustering, based on psychiatric symptomatology levels, derived from The Strength and Difficulties Questionnaire - Parent Form and The Revised Children's Anxiety and Depression Scale - Parent Form: with one group exhibiting lower reported psychiatric symptoms (LPS=27) and the other demonstrating higher psychiatric symptoms (HPS=8) by parents. RESULTS: Our study found that many parents were hesitant to disclose DSD diagnoses to their children, believing them to be too young to comprehend the information (42.9 %) and that they were unaware of the available support that could be provided by the medical team in disclosing the diagnosis (25.7 %). Our study found no differences in DSM-5 diagnoses between HPS and LPS groups (p>0.05), with ADHD being the most prevalent diagnosis (21.7 %) and a significant overrepresentation of children with a discrepancy between assigned gender at birth and gender upbringing in the HPS group compared to the LPS group (p<0.001). CONCLUSIONS: Our study emphasizes the necessity of a transdiagnostic approach in psychiatry to move beyond binary conceptualizations and better understand the complexities of individuals with DSD.

"Predicting diabetic kidney disease in youth with type 1 diabetes: Insights from genetic risk assessment".

OBJECTIVE: Diabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes. METHODS: The study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis. Genetic data and clinical data from diabetes diagnosis to moderately increased albuminuria (MIA) detection were compared between the groups. RESULTS: Among 43 DKD cases, 22 were girls and 21 were boys. At MIA diagnosis, mean body weight SDS was -0.24 ± 0.94, height SDS was 0.34 ± 1.15, and BMI SDS was -0.26 ± 0.94. Systolic blood pressure was at the 72nd percentile (2-99), and diastolic blood pressure was at the 74th percentile (33-99). Significant differences in rs267734, rs267738, and rs942263 polymorphisms were found between DKD and non-complication diabetic groups (13[30.2 %] vs 5[11.6 %], p = 0.034; 14[32.6 %] vs 5[11.6 %], p = 0.019; 26[60.5 %] vs 40[93 %], p < 0.001). CONCLUSION: Several factors were identified as significant in DKD onset, including low follow-up weight SDS, elevated diastolic blood pressure, presence of rs267734, and absence of rs942263 polymorphisms. The model demonstrated a specificity of 81.4 % and a sensitivity of 74.4 %.

Adherence to Growth Hormone Treatment in Children During the COVID-19 Pandemic

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 µg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Evaluation of Growth Characteristics and Final Heights of Cases Diagnosed with Noonan Syndrome on GH Treatment.

Introduction: Proportional short stature is one of the most important features of Noonan Syndrome, and adult height often remains below the 3rd percentile. Although the pathophysiology of short stature in NS patients is not fully understood, it has been shown that GH treatment is beneficial in NS, and it significantly improves the height in respect to the results of short and long-term GH treatment. Methods: In this study, the efficacy of GH therapy was evaluated in children and adolescents with Noonan syndrome who attained final height. In this national cohort study, 67 cases with NS who reached final height from 14 centers were evaluated. Results: A total of 53 cases (mean follow-up time 5.6 years) received GH treatment. Height SDS of the subjects who were started on GH tended to be shorter than those who did not receive GH (-3.26± 1.07 vs. -2.53 ±1.23) at initial presentation. The mean final height and final height SDS in girls using GH vs those not using GH were 150.1 cm and -2.17 SD vs 47.4 cm and-2.8 SD, respectively. The mean final height and final height SDS in boys using GH vs. not using GH were 162.48 ± 6.19 cm and -1.81 SD vs 157.46 ± 10.16 cm and -2.68 ± 1.42 SD, respectively. The Δheight SDS value of the cases was significantly higher in the group receiving GH than in those not receiving GH (1.36 ± 1.12 SD vs. -0.2 ± 1.24, p<0.001). Cardiac findings remained stable in two patients with hypertrophic cardiomyopathy who received GH treatment. No significant side effects were observed in the cases during follow-up. Conclusion: In patients with Noonan syndrome who reach their final height, a significant increase in height is observed with GH treatment, and an increase of approximately +1.4 SDS can be achieved. It has been concluded that GH treatment is safe and effective.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

OBJECTIVES: Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, is believed to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. METHODS: Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. RESULTS: None of the patients had known underlying cardiovascular disease. The mean age was 13.18 ± 2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42 ± 0.06 vs. healthy controls: 0.34 ± 0.04 mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97 ± 10.32 vs. 77.56 ± 8.50 %, (OI group: 7.00 ± 3.06 vs. healthy controls: 12.14 ± 1.99, p=0.56), and fractional shortening was 42.68 ± 11.94 vs. 40.23 ± 7.99 %, (p=0.35), in OI patients and controls, respectively. CONCLUSIONS: Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

ABCC8-related maturity-onset diabetes of the young: switching from insulin to sulphonylurea therapy: how long do we need for a good metabolic control?

OBJECTIVES: Activating variants of the ABCC8 gene cause neonatal diabetes or maturity-onset diabetes of the young (MODY). We report three cases of MODY type 12 caused by variants in the ABCC8 encoding sulphonylurea receptor 1, and the experience of switching from insulin therapy to sulphonylurea therapy. CASE PRESENTATIONS: We describe a 12.5-year-old girl with permanent neonatal diabetes mellitus, and two diabetes mellitus cases with variants in the ABCC8 gene. Two of these cases were successfully switched from subcutaneous insulin to oral glibenclamide, with a marked improvement in glycemic control. In permanent neonatal diabetes case, glibenclamide dose was progressively increased to achieve a full dose (2 mg/kg/day) in 9 days. Nine months after starting oral sulphonylurea therapy, her blood glucose control dramatically improved and insulin therapy was discontinued. CONCLUSIONS: We conclude that patients with ABCC8 gene variants can successfully switch from insulin to sulphonylureas.

Novel Modified Algorithm for High Fat/High Energy Density Meal in Type 1 Diabetes: Less Hypoglycemia

Objective: This aim of this study was to investigate the effect of additional insulin dosing for high fat/high energy density mixed meal over 12 hours. Methods: In this single-center, non-blinded, randomized, cross-over study, a high fat/high energy density test meal was used to study the impact on glycemic response of either carbohydrate counting (CC) on the first day and the Pankowska algorithm (PA) on the second test day. The two methods were compared in 20 adolescents with type 1 diabetes (T1D), aged 9-18 years, using insulin pump therapy and continuous glucose monitoring on postprandial early (0-120 min), late (120-720 min), and total (0-720 min) glycemic response. Results: There was no difference between groups in the duration of normoglycemia in the early period. Postprandially, 50% of patients developed hypoglycemia using the PA at a median of 6.3 (5.6-7.9) hours and the PA was subsequently modified for the remaining ten patients. Area under the curve (AUC) for the early period decreased non-significantly in the CC group, indicating less normoglycemia. No significant difference was found in the AUC of the PA (no hypoglycemia n=4) and modified PA groups (no hypoglycemia n=6) over the whole period (0-12 hours). AUC for level 2 hyperglycemia was statistically greater in the PA-no hypoglycemia patients compared to modified PA-no hypoglycemia patients. Conclusion: There were inter-individual differences in glycemic response to high fat/high energy density meals. An individualized approach to insulin dosing by evaluating food diary and postprandial glucose monitoring appears to be optimal for children and adolescents with T1D.

Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition.

OBJECTIVES: Familial transmission is observed in approximately 10% of cases with type 1 diabetes mellitus (T1DM). The most important gene determining susceptibility is the human leukocyte antigen complex (HLA) located on chromosome 6. More than 50 susceptible loci are associated with T1DM susceptibility have been identified in genes other than HLA. In this study, it was aimed to investigate the molecular genetic etiology by whole-exome sequence (WES) analysis in cases with familial T1DM with no or weakly detected HLA tissue type susceptibility. We aimed to identify new genes responsible for the development of type 1 diabetes and to reveal new genes that have not been shown in the literature before. METHODS: Cases with at least one T1DM diagnosis in first-degree relatives were included in the study. In the first step, HLA DQ2 and DQ8 loci, which are known to be associated with T1DM susceptibility, were investigated by. In the second step, the presence of variants that could explain the situation was investigated by WES analysis in patients who were negative for both HLA DQ2 and HLA DQ8 haplotypes, HLA DQ2 negative, HLA DQ8 positive, and HLA DQ2 positive and HLA DQ8 negative patients. RESULTS: The mean age and duration of diabetes of the 30 cases (Girl/Male: 17/13) were 14.9 ± 6 and 7.56 ± 3.84 years, respectively. There was consanguineous marriage in 5 (16%) of the families. As a result of filtering all exome sequence analysis data of two cases with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (-), seven cases with DQ2 (DQB1*02) (+) and DQ8 (DQB1*03:02) (-), and one case with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (+), seven different variants in seven different genes were detected in five cases. The pathogenicity of the detected variants were determined according to the "American College of Medical Genetics and Genomics (ACMG)" criteria. These seven variants detected were evaluated as high-score VUS (Variants of unknown/uncertain significance). In the segregation study conducted for the mutation in the POLG gene detected in case 5, this variant was detected in the mother of the case and his brother with T1DM. Segregation studies are ongoing for variants detected in other affected individuals in the family. CONCLUSIONS: In conclusion, in this study, seven different variants in seven different genes were detected in five patients by WES analysis in familial T1DM patients with no or weak HLA tissue type susceptibility. These seven variants detected were evaluated as high-score VUS. POLG might be a novel candidate gene responsible for susceptibility to T1DM. Non-HLA genes directly responsible for the development of T1DM were not detected in any of the cases.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Objectives: Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. Methods: We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. Results: FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). Conclusion: FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.