Şenay Savaş Erdeve

Relationships Between Osteocalcin, Glucose Metabolism, and Adiponectin in Obese Children: Is there Crosstalk Between Bone Tissue and Glucose Metabolism?

Objective: Recently, scientific interest has focused on the association between osteocalcin, which originates from the skeletal system, and glucose metabolism. Although the association between lipid metabolism, adiponectin, and metabolic syndrome is well known, that between obesity, insulin resistance, and osteocalcin have not been clarified yet in children. The aim of this study was to assess the prevalence of insulin resistance in obese children and adolescents, as well as to investigate the effects of adiponectin and osteocalcin on the development of metabolic syndrome and insulin resistance. Methods: A total of 150 obese nondiabetic children and adolescents, aged between 5 and 18 years, were included in the study. Serum adiponectin, osteocalcin and insulin levels were measured, and the association of the components of metabolic syndrome with adiponectin and osteocalcin levels was investigated. Insulin resistance was evaluated by Homeostasis model assessment insulin resistance (HOMA-IR). Results: Metabolic syndrome was identified in 28% of the cases, all older than 10 years of age. No significant association was identified between insulin resistance, metabolic syndrome parameters, and osteocalcin levels. Adiponectin levels were significantly low in cases with metabolic syndrome, hyperinsulinemia, and in those with dyslipidemia. No significant association was found between adiponectin and osteocalcin levels. Conclusions: We failed to show the effect of osteocalcin on insulin resistance in obese children and adolescents. This finding may be due to absence of hypergycemic blood glucose levels in our cases. Conflict of interest:None declared.

The clinical and genetic heterogeneity of mixed gonadal dysgenesis: does “disorders of sexual development (DSD)” classification based on new Chicago consensus cover all sex chromosome DSD?

Clinical findings illustrate the wide spectrum of the phenotypic manifestations of 45,X/46,XY mosaicism in the sex chromosome disorders of sex differentiation (DSD). The objective of study is to evaluate the characteristics of 45,X/46,XY patients and questioning of their place within the DSD categorization. The clinical findings of 11 patients with 45,X/46,XY mosaicism are described including the presentation, gonadal morphology, genital anatomy, and the hormone levels among 285 patients with DSD evaluated. Sixty-seven patients were diagnosed with sex chromosome DSD (50 Turner, three Klinefelter, ten 45,X/46,XY gonadal disgenesis, one 45X/46,XY ovotesticular DSD, one 47,XYY ovotesticular DSD, and two 46,XX/46,XY ovotesticular DSD). The type and the percentage of patients with 45,X/46,XY mosaicism were as follows: Four cases of mix gonadal dysgenesis, four cases of partial gonadal dysgenesis, two cases of complete gonadal dysgenesis, one case of ovotesticular DSD. On the other hand, another patient that has 45,X/46,XX mosaicism was diagnosed with MGD with the presence of the streak gonad on the right side and the testis on the other side. Conclusion: We suggest that sex chromosome DSD categorization can include 45,X/46,XY PGD and 45,X/46,XY CGD. Mixed gonadal dysgenesis may be also placed among the disorders of testicular differentiation of 46,XY DSD subdivision.

Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell

Abstract Background: Recessive mutations in ABCC8/KCNJ11 of β-cell KATP channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. Subjects: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited KATP channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive KATP channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. Conclusion: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.

Transient neonatal diabetes with two novel mutations in the KCNJ11 gene and response to sulfonylurea treatment in a preterm infant.

Abstract Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. KATP channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission.

Evaluation of hypercoagulability in obese children with thrombin generation test and microparticle release: effect of metabolic parameters.

Obesity is associated with a hypercoagulable state. Thrombin generation test (TGT) and microparticle levels were not studied in obese children extensively. It is aimed to determine whether any differences in the coagulation system between obese and normal weighed children exist with the use of TGT and microparticles release. A total of 120 obese and 38 healthy children were included to the study. An increase of thrombin generation and microparticles levels were found in obese children. Hyperinsulinism could not find a risk factor for hypercoagulability in our obese children. None of the parameters of TGT has been shown to be related to metabolic parameters and metabolic syndrome. Microparticles release time is found to correlate only to body mass index (BMI) Standard deviation score (SDS) in obese children. Hypercoagulability is associated with childhood obesity. Significant correlation between degree of obesity and microparticles release suggested that high adipokine levels secreted from adipose tissue can stimulate procoagulant status-independent metabolic dearrangements.

Clinical Review of 95 Patients with 46,XX Disorders of Sex Development Based on the New Chicago Classification

STUDY OBJECTIVE The aim of our study was to determine the etiologic distribution of 46,XX disorder of sexual development (DSD) according to the new DSD classification system and to evaluate the clinical features of this DSD subgroup in our patient cohort. PARTICIPANTS The evaluation criteria and clinical findings of 95 46,XX patients were described by clinical presentation, gonadal morphology, genital anatomy, associated dysmorphic features, presence during prenatal period with/without postnatal virilization, hormonal characteristics, and presence or absence of steroidogenic defects among 319 patients with DSD. RESULTS Types and ratios of each presentation of our 95 patients with 46,XX DSD were as follows: 82 had androgen excess (86.3%): (74 had classical congenital adrenal hyperplasia, 2 had CAH variant possibility of P450-oxidoreductase gene defect), 6 had disorders of ovarian development (6.3%): (1 patient had gonadal dysgenesis with virilization at birth with bilateral streak gonad, 4 patients had complete gonadal dysgenesis, and 1 patient had ovotesticular DSD) and 7 had other 46,XX DSD. Two sisters, who had 46,XX complete gonadal dysgenesis,were diagnosed with Perrault Syndrome with ovarian failure due to streak gonads and associated with sensorineural deafness. CONCLUSION 46,XX DSD are usually derived from intrauterine virilization and CAH is the most common cause of 46,XX DSD due to fetal androgen exposure.

Preperitoneal Fat Tissue May Be Associated with Arterial Stiffness in Obese Adolescents

Vascular aging is a chronic process, and many negative effects of obesity in this process have been well defined. We assessed arterial stiffness in obese adolescents and evaluated the relationship between intra-abdominal fat distribution and arterial stiffness. Arterial stiffness parameters and pulse wave velocity (PWV) were evaluated in 61 obese adolescents and 58 healthy controls. Carotid-femoral PWV was calculated by arterial tonometry. Additionally, all obese children were evaluated for metabolic syndrome and insulin resistance. Intra-abdominal fat distribution, including subcutaneous, preperitoneal and visceral fat thicknesses, was assessed by ultrasonography. PWVs of obese children were significantly higher than those of healthy controls (5.0 ± 0.7 m/s vs. 4.7 ± 0.5 m/s). Parameters affecting PWV were evaluated by regression analysis. The independent variable in the regression analysis model was PWV, and the dependent variables were age, metabolic syndrome, body mass index and Homeostasis Model Assessment--Insulin Resistance, as well as subcutaneous, preperitoneal and visceral fat tissue thicknesses measured by ultrasonography. The only parameter associated with PWV was preperitoneal fat tissue thickness. Vascular changes related to obesity may begin in adolescence, as illustrated by the increased PWV. Preperitoneal fat tissue may be related to arterial stiffness. Intra-abdominal fat distributions obtained by ultrasonography may provide clinicians with valuable information needed to determine cardiovascular disease risk factors in obese adolescents.

Case report: two patients with partial DiGeorge syndrome presenting with attention disorder and learning difficulties.

DiGeorge syndrome (DGS) has classically been characterized by the triad of clinical features including congenital cardiac defects, immune deficiencies secondary to aplasia or hypoplasia of the thymus, and hypocalcaemia due to small or absent parathyroid glands. The phenotypic features of these patients are much more variable and extensive than previously ecognized. The acknowledgement of similarities and phenotypic overlap of DGS with other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of DGS including palatal/speech abnormalities, as well as cognitive, neurological and psychiatric disorders. Here, we report the cases of two DGS patients with dysmorphic facial features who were initially admitted to the Psychiatry Department for attention disorder and learning difficulties. Conflict of interest:None declared.

Amiodarone-induced Thyrotoxicosis in Children and Adolescents is a Possible Outcome in Patients with Low Iodine Intake

ABSTRACT Background/Objective The identification of the different subtypes of amiodarone-induced thyrotoxicosis (AIT) may provide a rational basis for the choice of the appropriate medical treatment. The aim of this study was to evaluate differential diagnosis and treatment regimens of AIT in children and adolescent. Patients We reported 3 patients: A 6.7 years old boy with type I AIT a 17.9 years old girl with type II AIT and a 14.6 years old girl with mixed type AIT. Conclusions AIT is not an uncommon complication in countries with low iodine intake. AIT can be asymptomatic and can occur at any time in patients receiving amiodarone therapy. It is also very important to distinguish the type of AIT when planning therapy. Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued.

Synchronous occurrence of papillary carcinoma in the thyroid gland and thyroglossal duct in an adolescent with congenital hypothyroidism.

Thyroid carcinoma (TC) combined with congenital hypothyroidism is rare. The synchronous occurrence of these two conditions is even rarer. We describe a patient with congenital hypothyroidism in whom hyperthyroglobulinemia and nodules developed despite adequate replacement therapy. Papillary TC was detected at age 19 years. Postoperative diagnostic scintigraphy showed increased uptake in the thyroglossal duct region. Repetitive imaging of the thyroid gland can be useful in the early detection of TC in patients with congenital hypothyroidism. Moreover, this rare situation can be complicated by a synchronous thyroglossal duct carcinoma. Thyroglossal duct carcinoma can be detected if diagnostic scintigraphy is performed after total thyroidectomy. Conflict of interest:None declared.