Clinical and Laboratory Characteristics of MODY (Maturity Onset Diabetes of Young) Cases, Genetic Mutation Spectrum and Phenotype-genotype Relationship.

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

Pteridine and tryptophan pathways in children with type 1 diabetes: Isoxanthopterin as an indicator of endothelial dysfunction.

AIM: Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be used as biomarkers in the evaluation of oxidative stress. In this study, our aim is to compare the concentrations of serum and urinary pteridine derivatives, as well as serum IDO activity, in children and adolescents diagnosed with T1D and those in a healthy control group. METHOD: A cross-sectional study was performed and included 93 patients with T1D and 71 healthy children. Serum and urine biopterin, neopterin, monapterin, pterin, isoxanthopterin, and pterin-6-carboxylic acid (6PTC) and serum tryptophan and kynurenine levels were analyzed and compared with healthy controls. High-performance liquid chromatography was used for the analysis of pteridine derivatives, tryptophan, and kynurenine. Xanthine oxidase (XO) activity, a marker of oxidative stress, was defined by measurement of serum and urine isoxanthopterin. As an indicator of indolamine 2,3-dioxygenase (IDO) activity, the ratio of serum kynurenine/tryptophan was used. RESULTS: Serum isoxanthopterin and tryptophan concentrations were increased, and serum 6PTC concentration was decreased in children with T1D (p=0.01, p=0.021, p<0.001, respectively). In children with T1D, IDO activity was not different from healthy controls (p>0.05). Serum neopterin level and duration of diabetes were weakly correlated (p=0.045, r=0.209); urine neopterin/creatinine and isoxanthopterin/creatinine levels were weakly correlated with HbA1c levels (p=0.005, r=0.305; p=0.021, r=0.249, respectively). Urine pterin/creatinine level negatively correlated with body mass index-SDS. (p=0.015, r=-0.208). CONCLUSION: We found for the first time that isoxanthopterin levels increased and 6PTC levels decreased in children and adolescents with T1D. Elevated isoxanthopterin levels suggest that the XO activity is increased in TID. Increased XO activity may be an indicator of vascular complications reflecting T1D-related endothelial dysfunction.

Acute Kidney Injury After Thyroid Hormone Withdrawal in an Adolescent with Papillary Thyroid Carcinoma.

Objectives: We report a patient with papillary thyroid carcinoma (PTC) who developed acute kidney injury (AKI) and elevated creatine kinase (CK) after thyroid hormone withdrawal (THW) prior to radioiodine therapy. Case presentation: A 12-year-old female patient who had undergone total thyroidectomy for PTC one year ago presented with leg pain for the past 2 days. Following THW 3 weeks ago, the case had received 70 mCI radioiodine treatment 6 days ago. Serum creatinine (1.53 mg/dL, normal range [NR]: 0.3-1.1), aspartate aminotransferase (102 IU/L, NR: 0-40) and CK (3451 IU/L, NR: 26-174) levels were elevated. Thyrotropin level was elevated (>100 µIU/ml, NR: 0.51-4.3), and free T4 level was decreased (0.05 ng/dL, NR: 0.98-1.63). Serum creatinine and CK levels decreased after intravenous hydration and levothyroxine treatment. Conclusion: In PTC cases with thyroidectomy, kidney function and CK elevation should be assessed after THW and dehydration should be prevented.

Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

Differentiated Thyroid Cancer in Children and Adolescents: Clinicopathological Characteristics of 32 Patients Followed up in our Pediatric Endocrinology Unit.

Objectives: This study aims to investigate the clinical and pathological features of patients with differentiated thyroid cancer (DTC) treated at our tertiary care institution. Methods: Thirty-two children and adolescents followed up with the diagnosis of DTC between 2001 and 2017 were enrolled. We classified patients with DTC into two groups as below and above 10 years of age, and compared their clinical and pathological features. Results: The mean age at presentation was 11.2±4 years. The female/male ratio was 7 (28:4). The diagnosis was papillary thyroid cancer (PTC) in 90.6% (n=29). The frequencies of lymph node and pulmonary metastases were 53.1% and 21.8%, respectively. The groups were comparable in terms of gender, initial clinical signs and tumor histopathology. The mean tumor size was greater in the younger age group (p=0.008). However, there was no difference between the two groups in terms of lymph node and pulmonary metastases. The pathological parameters associated with tumor aggressiveness were also similar between the groups, except lymphovascular invasion. Lymphovascular invasion was more frequent in the younger age group (p=0.01). Patients with lymph node and pulmonary metastases were more likely to have extrathyroidal extension and lymphovascular invasion. Conclusion: PTC was the most common type of DTC and presented with considerable rates of lymph node and pulmonary metastases. Tumor size was greater and lymphovascular invasion was more common in younger patients. Overall prognosis was favorable despite high rates of lymph node and pulmonary metastases.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

Clinical indicators that influence a clinician's decision to start L-thyroxine treatment in prematurity with transient hypothyroxinemia.

BACKGROUND: Transient hypothyroxinemia of prematurity (THOP) is defined as a low level of circulating thyroxine (T4), despite low or normal thyroid-stimulating hormone (TSH) levels. AIMS: We aimed to evaluate the incidence of THOP, the clinical and laboratory findings of preterm infants with this condition and the levothyroxine (L-T4) treatment. METHODS: Preterm infants (n = 181) delivered at 24-34 weeks of gestation were evaluated by their thyroid function tests that were performed between the 10th and 20th days of postnatal life and interpreted according to the gestational age (GA) references. Clinical and laboratory characteristics of the patients with THOP and normal thyroid function tests were compared. Patients with THOP and treated with L-T4 were compared with the ones who were not regarding laboratory, and clinical characteristics. RESULTS: Incidence of hypothyroxinemia of prematurity was 45.8% (n = 83). Euthyroidism, primary hypothyroidism, and subclinical hypothyroidism were diagnosed in 47.5% (n = 86), 5% (n = 9) and 1.7% (n = 3) of the patients, respectively. Mean birth weight (BW) and GA were significantly lower in the hypothyroxinemia group than in the euthyroid group (p < 0.001). L-T4 was started in 43% (n = 36) of the patients with THOP. Treatment initiation rate was 44.4% (n = 16) in 24-27 wk, 41.6% (n = 15) in 28-30 wk, and 13.8% (n = 5) in 31-34 wk. As the GA increased, the incidence of THOP and the rate of treatment initiation decreased (p < 0.001). The lowest free thyroxine (FT4) cut-off value was 0.72 ng/dl in the treated group. In addition, incidences of vancomycin + amikacin, caffeine, dopamine treatments, RDS, IVH, BPD, central catheter, FFP transfusion, and ventilator support were higher in the treated group (P < 0.05). CONCLUSION: This study revealed that prevalence of THOP increased as the GA and BW decreased. As the GA decreased, THOP patients requiring L-T4 treatment increased. Additionally, association with comorbid diseases increased the requirement of treatment.

Thyroid Nodules in Children and Adolescents: A Single Institution's Experience.

OBJECTIVE: The risk of malignancy in pediatric thyroid nodules is higher compared to the risk in adults. Our aim was to investigate the clinical, radiological, and histopathological characteristics of pediatric thyroid nodules. MATERIALS AND METHODS: The data of 132 children and adolescents who had thyroid nodules were collected retrospectively from medical records. RESULTS: The mean age of the patients was 12.07 ± 4.08 years and 67% were female. Fine-needle aspiration biopsy was performed in 86 patients (65%) and the results were as follows: benign in 53.4% (n = 46), atypia or follicular lesion of undetermined significance in 3.5% (n = 3), suspicious for follicular neoplasia in 2.3% (n = 2), and malignancy in 32.5% (n = 28). The overall malignancy rate was 22.7% (n = 30). Malignancy was detected after surgery in 2 thyroid nodules belonging to the atypia or follicular lesion of undetermined significance category. Malignancy was detected in 7 patients who had autoimmune thyroiditis and in 1 patient who had congenital dyshormonogenesis. The malignancy rate of the nodules in the patients, who had autoimmune thyroiditis, was found to be 13.4%. Mixed echogenicity, microcalcifications, nodules larger than 10 mm, abnormal lymph nodes, and irregular borders were more common in the malignant group. The nodule size, abnormal lymph nodes, and irregular borders were found to be significant in terms of predicting malignancy. CONCLUSION: We found malignancy in 22.7% of the thyroid nodules, and the malignancy rate of nodules in the patients, who had autoimmune thyroiditis, was 13.4%. The nodule size, abnormal lymph nodes, and irregular nodule borders emerged as the most significant risk factors for malignancy.

Left Ventricular Systolic Dysfunction Related to Adrenal Insufficiency in a Case due to Autoimmune Polyendocrine Syndrome Type 1 with a Novel Variant.

Introduction: Primary adrenal insufficiency associated with cardiomyopathy has been rarely reported in children. We report a case of left ventricular (LV) systolic dysfunction related to adrenal insufficiency with autoimmune polyendocrine syndrome type 1 (APS1). Case Presentation: A 7-year-old girl presented with a loss of consciousness. She had hyperpigmentation over joints and enamel hypoplasia. Laboratory tests showed hypoglycemia, hyponatremia, hypocalcemia, and hyperphosphatemia. Endocrine evaluations revealed low serum parathyroid hormone, low cortisol, and high ACTH. Echocardiography showed moderate to severe mitral regurgitation and LV systolic dysfunction. Serum pro-brain natriuretic peptide (pro-BNP) level was high (2,348 pg/mL). Adrenal insufficiency, hypoparathyroidism, and enamel dysplasia suggested APS1. A novel homozygous variant in the AIRE gene, NM_000383, p.Cys322Arg (c.964T>C) confirmed the diagnosis. Calcium, calcitriol, and hydrocortisone treatments were started. Serum pro-BNP level returned to normal, and LV systolic function improved. Conclusion: Here, we present a case of adrenal insufficiency and hypoparathyroidism associated with LV systolic dysfunction whose cardiac findings improved completely with hydrocortisone and calcitriol treatments. Our case is the second reported case of APS1 presenting with LV dysfunction.

Evaluation of the left ventricular systolic function and myocardial deformation by real-time three-dimensional (four-dimensional) and speckle-tracking echocardiography in children with type 1 diabetes mellitus.

AIM: This study aimed to evaluate the role of real-time three-dimensional (known as four-dimensional) echocardiography and three-dimensional speckle-tracking echocardiography for the early detection of left ventricular systolic dysfunction in asymptomatic children with type 1 diabetes mellitus. MATERIALS AND METHOD: This cross-sectional study included 38 patients (mean age 15.4 ± 2.9, 42.1% male) and 38 age, gender, and body measurements matched healthy children. Each patient underwent an interview about medical history, a detailed clinical examination, blood laboratory tests, conventional echocardiography, and tissue Doppler imaging. Left ventricular ejection fraction; global longitudinal, circumferential, radial strain; twist; and torsion were measured by real-time three-dimensional and speckle-tracking echocardiography. RESULTS: Conventional echocardiography and tissue Doppler imaging showed normal left ventricular systolic function in the patients. Although left ventricular ejection fraction (61.6 ± 1.4%, 61.8 ± 1.1%, p = 0.386), global longitudinal [-26.6 (-27.7 to -26.1)%, -26.2 (-27.7 to -24.9)%, p = 0.224], and radial strain [44.4 (42.4-45.9)%, 43.9 (41-46.1)%, p = 0.513] were similar to the controls, circumferential strain (-27.3 ± 1.3%, -28.0 ± 1.6%, p = 0.048) and twist (9.5 ± 2.3°, 11.4 ± 3.0°, p = 0.003) were decreased in the patients compared with controls. CONCLUSION: We found that even in children with asymptomatic type 1 diabetes mellitus with normal left ventricular ejection fraction, circumferential function was impaired and rotation pattern was changed. This novel echocardiographic method might be an important tool for detecting left ventricular systolic dysfunction in type 1 diabetes mellitus children before it becomes overt on conventional echocardiography and tissue Doppler imaging.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Elevated Urinary VEGF-A, Transferrin, and Angiotensinogen Levels in Normoalbuminuric Children and Adolescents with Type 1 Diabetes: Can They Be Early Markers of Diabetic Kidney Disease?

OBJECTIVE: We hypothesized that diabetic kidney disease (DKD) begins early, before albuminuria occurs. We therefore aimed to assess potential early urinary biomarkers of DKD in normoalbuminuric and normotensive children and adolescents with type 1 diabetes (T1D) to evaluate the relationship between these markers and clinical and laboratory risk factors for DKD. METHODS: This cross-sectional study included 75 children and adolescents with T1D (62% females, mean age 13.9 ± 3.2 years) with normoalbuminuria (an albumin/creatinine ratio [ACR] below 30 mg/g creatinine). Fifty-five age- and sex-matched healthy children and adolescents served as controls. For the assessment of early DKD, urinary levels of angiotensinogen (AGT), transferrin, nephrin, vascular endothelial growth factor-A (VEGF-A), and kidney injury molecule-1 (KIM-1) were measured in adequately collected 24-h urine samples using enzyme-linked immunoassays. RESULTS: The mean disease duration was 7.3 ± 3.2 (range 2.1-15.7) years, and the mean HbA1c level was 8.8 ± 1.4%. The median levels of urine VEGF-A/Cr, AGT/Cr, and transferrin/Cr were significantly higher in normoalbuminuric patients with T1D, compared with those of controls (p < 0.001, p = 0.02, and p = 0.001, respectively), but there was no difference in nephrin/Cr and KIM-1/Cr between the 2 groups. Although none of the patients had albuminuria, the median level of urine ACR was significantly higher in the patient group than the control group (p = 0.003). The ACR was positively correlated with glomerular filtration rate (GFR). Urinary transferrin/Cr, AGT/Cr, and VEGF-A/Cr were significantly correlated with ACR, but not with either GFR or diabetic risk factors including HbA1c or disease duration. CONCLUSION: Normoalbuminuric and normotensive children and adolescents with T1D have elevated urinary VEGF, AGT, and transferrin levels, which may indicate the development of DKD before albuminuria occurs.

The factors associated with transient hypothyroxinemia of prematurity.

BACKGROUND: Hypothyroxinemia is defined by low levels of thyroxine (T4) despite low or normal levels of thyroid-stimulating hormone (TSH). This study aimed to evaluate the factors associated with transient hypothyroxinemia of prematurity (THOP) in newborns admitted to the neonatal intensive care unit (NICU). METHOD: This is a single center, retrospective, case-control study. Premature newborns, between 24 and 34 weeks of gestation, hospitalised between January 2014-December 2019 in Istanbul University-Cerrahpasa Faculty of Medicine NICU were analyzed through their medical records. Thyroid function tests were routinely performed between the 10th and 20th days of postnatal life and were evaluated according to the gestational age references. Thirty six possible associated factors (prenatal and postnatal parameters, medical treatments, clinical diagnoses and applications in NICU) were searched in the patient group with THOP (n = 71) and the control group with euthyroid prematures (n = 73). The factors for THOP were identified by univariate analysis, followed by multivariate analysis. RESULTS: Mean gestational ages of the study and the control groups were 29.7 ± 2.48 and 30.5 ± 2.30 weeks, respectively (p = 0.606). The birth weight, small for gestational age (SGA), intraventricular hemorrhage (IVH), congenital heart disease (CHD) were found to be the possible associated factors for THOP in the univariate analysis and CHD (p = 0.007, odds ratio [OR]:4.9, 95% confidence interval [CI]: 1.5-15.8), BW (p = 0.004, OR:0.999, 95% CI: 0.9-1.0) and SGA (p = 0.010, OR:4.6, 95% CI: 1.4-14.7) were found to be factors associated with THOP determined by univariate logistic regression analysis. CONCLUSiONS: Although some treatment practices might have had direct effects on pituitary-thyroid axis, related with the severity of the newborn clinical conditions, non of them was found to be a associated factor for THOP. However, CHD and SGA may be considered as associated factors with THOP detected in preterm infants.

Molecular Diagnosis of Monogenic Diabetes and Their Clinical/Laboratory Features in Turkish Children

Objective: Monogenic diabetes is a heterogeneous disease that causes functional problems in pancreatic beta cells and hyperglycemia. The aim of this study was to determine the clinical and laboratory features, the admission characteristics and distribution of monogenic form of diabetes in childhood in Turkey. Methods: Patients aged 0-18 years, who were molecularly diagnosed with monogenic diabetes, and consented to participate, were included in the study. Results: Seventy-seven (45.6%) female and 92 male cases with a mean age of 8.18±5.05 years at diagnosis were included. 52.7% of the cases were diagnosed with monogenic diabetes by random blood glucose measurement. The reason for genetic analysis in 95 (56.2%) of cases was having a family member diagnosed with diabetes under the age of 25. At the time of diagnosis, ketone was detected in urine in 16.6% of the cases. Mean hemoglobin A1c on admission, fasting blood glucose, fasting insulin, and c-peptide values were 7.3±2.1%, 184.9±128.9 mg/dL, 9.4±22.9 IU/L, 1.36±1.1 and ng/L respectively. GCK-MODY was found in 100 (59.2%), HNF1A-MODY in 31 (18.3%), and variants in ABCC8 in 6 (3.6%), KCNJ11 in 5 (3%), HNF4A in 2 (1.2%), and HNF1B in 2 (1.2%). Conclusion: Recent studies have indicated HNF1A-MODY is the most frequent of all the MODY-monogenic diabetes cases in the literature (50%), while GCK-MODY is the second most frequent (32%). In contrast to these reports, in our study, the most common form was GCK-MODY while less than 20% of cases were diagnosed with HNF1A-MODY.

Clinical, biochemical, and radiological follow-up results of children and adolescents with Hashimoto's thyroiditis: a single-center experience.

OBJECTIVES: Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children and adolescents, especially in areas without endemic iodine deficiency. We aimed to evaluate the follow-up results of children and adolescents diagnosed with HT, including clinical, biochemical, and radiological findings and treatment approaches. METHODS: HT patients, who were diagnosed between 2012 and 2018 years in a single-center, were assessed retrospectively. RESULTS: Two hundred and twenty-four cases were included in the study, 75.9% of whom were girls (female/male ratio: 3.1) and 66.5% were pubertal. The median age of the cases at first admission was 12.5 (9.2-15) years. The median follow-up period of 196 patients, who continued their follow-up regularly, was 2.1 (0.7-4.8) years. When autoantibody levels were analyzed according to gender, mean anti-Tg levels were higher in girls (p=0.028), whereas anti-TPO levels were similar (p=0.372). A nodule was detected in the ultrasonographic follow-up of 29 (13%) patients. Papillary thyroid carcinoma was observed in 10.3% (n=3) of those with nodules. When the last ultrasonography findings of 188 patients with available radiological follow-up data were compared with their initial evaluation, the rate of heterogeneous parenchymal echogenicity increased significantly (p=0.008). The need for l-thyroxine dosage augmented over time. CONCLUSIONS: Although HT is more common in adolescent girls, it can be encountered in both genders and at all ages in childhood. The incidence of malignancy was not higher in patients with nodules associated with HT than the reported incidences of malignancy in nodules not associated with HT.

Different clinical entities of the same mutation: a case report of three sisters with Wolfram syndrome and efficacy of dipeptidyl peptidase-4 inhibitor therapy.

OBJECTIVES: Wolfram syndrome (WS) is a rarely seen autosomal recessive multisystem neurodegenerative disorder caused by mutations in the WFS1 gene. CASE PRESENTATION: Three sisters with WS had diabetes mellitus (DM) at 4 years of age and optic atrophy. In addition, the first case had hearing impairment, and the second case had diabetes insipidus and urinary incontinence. Linagliptin was administered to the first case as add-on therapy to intensive insulin treatment 15 years after the onset of DM, and her insulin need showed a dramatic decrease. The third case had a remission phase one month after the onset of DM. CONCLUSIONS: Even in cases with the same mutation, symptoms and findings may widely vary in WS. Remission of diabetes has rarely been reported in WS. Also, this report describes the first trial of a dipeptidyl peptidase-4 inhibitor in a patient with WS which provided a decrease in exogenous insulin need.

A rare intrauterine onset growth retardation syndrome caused by mosaic 19p13.3 microduplication: evaluation of GH/IGF- 1 axis and GH therapy response.

BACKGROUND: 19p13.3 microduplication syndrome is a newly defined intrauterine onset growth retardation syndrome characterized by microcephaly, moderate intellectual disability, speech delay, and mild dysmorphic features. The PIAS4 gene located in this region plays a crucial role as a transcriptional co-regulator in various cellular pathways including STAT, p53/TP53 and growth hormone (GH) signaling and mutations in this gene are thought to be responsible for clinical features. CASE: We present a 10 year-old girl with intrauterine onset growth retardation, microcephaly, and mild facial dysmorphic features. Treatment with GH was started at 4 years and 9 months of age targeting the severe short stature (-3.65 standard deviation score, SDS) since she had significant IGF-1 response to exogenous GH. Microarray study demonstrated a 19p13.3 microduplication of 4.4 Mb. FISH analyses revealed mosaic extra signals (27.5% on blood lymphocytes, and 47% on buccal epithelium) of 19p13.3 region. At the age of 10, her height was at -2.37 SDS, and she had mild intellectual disability which has been described in 19p13.3 microduplication syndrome. CONCLUSION: We present here a patient with typical findings of 19p13.3 microduplication syndrome and also with a prominent response to GH treatment, which has not been reported previously in this syndrome.

Gonadectomy in conditions affecting sex development: a registry-based cohort study.

OBJECTIVES: To determine trends in clinical practice for individuals with DSD requiring gonadectomy. DESIGN: Retrospective cohort study. METHODS: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. RESULTS: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. CONCLUSIONS: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.