Aim: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow‐up. Methods: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow‐up was 86 ± 78 months. Results: The Kaplan–Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan–Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan–Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan–Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow‐up period. Causes of death were end‐stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. Conclusions: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Context Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. Objective To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. Methods Our cohort included 18 patients (LEP = 11, LEPR = 7), eight of whom had been previously reported. A systematic literature review was conducted in July 2022. 42/47 studies on LEP/LEPR were selected. Results Of 10 new cases, two novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40+5G>C). Eleven patients with LEP deficiency received metreleptin, four of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age (3 (9) vs. 7 (13) years, p = 0.02), and had a higher median BMI SD score (3.1 (2) vs. 2.8 (1) kg/m2, p = 0.02), which was more closely associated with frameshift variants (p = 0.02). Patients with LEP deficiency were more likely to have hyperinsulinemia (p = 0.02). Conclusion Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefited from long-term metreleptin, with one losing efficacy due to neutralizing antibodies.

Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n=3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral antidiabetic treatment. This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.

We aimed to evaluate the clinical, radiological and pathological findings of children and adolescents with thyroid nodules. Data of 121 children and adolescent with thyroid nodule and had fine needle aspiration (FNA) were examined retrospectively. Concomitant thyroid disease, ultrasound (US) features of the nodule, FNA and histopathological results were recorded. FNA results were assessed according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Median age of the cases was 14 years (range 3-18 years) and 81% were female. FNA results of patients were insufficient in 1 (0.8%), benign in 68 (56.2 %), indeterminate in 44 (36.4%) and malignant in 8 (6.6%) patients. Among 39 patients who were directed to surgery, 10 patients had differentiated thyroid cancer (DTC). The total malignancy rate was 10.0% (10/100). Control FNA results showed progress according to TBSRTC in 18.7% of benign results and 4 of 75 patients had DTC in surgical excision. 2 of 22 patients with atypia of undetermined significance (AUS) who continued follow-up was diagnosed with DTC. Male gender, presence of Hashimoto thyroiditis and US findings of uninodularity; hypoechogenicity; increased blood flow; irregular margins; solid structure; microcalcification and presence of abnormal cervical lymph nodes were associated with malignancy. Our results revealed that, thyroid nodules are 10% malignant in children and adolescents. Patients with AUS has 9% potential for malignancy and patients with initially benign FNA result may have changes in TBSTRC findings in repeat FNA with a 5.3% false negative rate.

Objectives: To examine sleep and behavior problems in children with type 1 Diabetes Mellitus (T1DM) compared to nondiabetic controls in a bridging country between east and west and to evaluate the interaction of sleep on behavior problems, maternal sleep, and maternal depressive symptoms. Methods: The study included children with T1DM (4–12 years old) and age/sex-matched healthy controls. Parents completed the Children Sleep Habits Questionnaire (CSHQ), Children Behavior Checklist/4–18 (CBCL/4–18), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and a study-specific sociodemographic questionnaire. Clinical parameters regarding T1DM were collated from medical records. Results: Participants included 75 children with T1DM and 49 controls. Based on CSHQ results 65.3% of all participants in both groups had sleep problems. Children with T1DM slept less and had higher daytime sleepiness problems than controls (p=0.024, p=0.008, respectively). No association was found between CSHQ or sleep duration and mode of diabetes treatment (pump, multiple daily injections) or glycemic control. CSHQ correlated with maternal PSQI (r=0.336 p=0.004) and BDI (r=0.341 p=0.004) in children with T1DM, but there was no association amongst controls. Children with T1DM had higher internalizing problems compared to controls. CSHQ and BDI correlated with internalizing, externalizing, and the total scores of the CBCL/4–18 in children with T1DM (R²=0.260 p<0.001; R²=0.207 p<0.001, R²=0.381 p<0.001 respectively). In controls, only BDI was associated with internalizing, externalizing, and the total scores of the CBCL/4–18. Conclusions: Children with T1DM should be evaluated for sleep pattern and quality at follow-up, to identify those at risk for behavior problems and improve maternal life quality. Large longitudinal studies are necessary to assess the effect of new diabetes treatment modalities on sleep.