Ayfer Alikasifoglu

Prevalence and risk factors of metabolic syndrome in obese children and adolescents: the role of the severity of obesity.

The present study was performed to determine the prevalence of metabolic syndrome (MS) and its risk factors in obese children and adolescents. The study included 352 obese children and adolescents (body mass index [BMI]u2009≥u200995th percentile) aged between 2 and 19xa0years. The diagnosis of MS was made according to the criteria adapted from the World Health Organization (WHO) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. BMI z-scores were calculated to assess the degree of obesity. The prevalence of MS and risk factors were determined. Determinants of MS were examined using regression analysis. The prevalence of MS was 41.8%. The age at onset of obesity, sedentary life-span, fasting blood levels of glucose, insulin, triglyceride, very-low-density lipoprotein (VLDL) cholesterol, and alanine aminotransferase (ALT) were higher, while levels of high-density lipoprotein (HDL) cholesterol and the number of actively spent hours were lower in cases with MS (pu2009<u20090.05). The most important determinant of MS was BMI z-score (ru2009=u20090.31, pu2009<u20090.0001). A one-point increase in BMI z-score yielded a 2-fold increase in the prevalence of MS. The prevalence of MS increased from 27.6% to 60.7% when the BMI z-score increased from 2.3 to 3.3. The risk of developing MS was 2.6-fold higher in cases with BMI z-scoreu2009>u20093 when compared to those with z-scores between 2 and 3. The results from this study indicate that, although the correlation between MS and the BMI z-score was weak, the BMI z-score may be an effective parameter in identifying obese children and adolescents at risk for MS. Screening the cases with BMI z-scoresu2009≥u20092 for MS is important for establishing an early diagnosis.

Endocrinological Outcome of Different Treatment Options in Children with Craniopharyngioma: A Retrospective Analysis of 66 Cases

Craniopharyngioma is one of the leading causes of hypothalamic-pituitary dysfunction in childhood, caused either by the tumor itself or the consequences of treatment. Tumor management in terms of recurrence rate, quality of life and complications is still controversial. Sixty-six patients with craniopharyngioma at pediatric age were reviewed for symptoms, signs, types of treatment, recurrence rates, complications, and endocrinological outcome. The majority of symptoms was related to the neurological system. Complaints only affecting the endocrinological system were seen in 6% of patients. The most frequent complaints were headache and vomiting (74.2%). The main endocrinological complaints were polyuria and polydipsia (15%), and lassitude (10.6%). Although short stature was a symptom in 9.1% of patients, it was a finding in 39.7% of patients. Plain skull X-rays raised the suspicion of intracranial tumor in more than 90% of children with craniopharyngioma. Recurrence rates were independent of the extent of tumor removal (total or subtotal). The frequency of endocrine dysfunction increased significantly after treatment. The most frequent hypothalamic-pituitary dysfunction was growth hormone deficiency (100%) and gonadotropin deficiency (80%). Hypothyroidism was diagnosed in 74% of patients. The frequency of hypothalamic-pituitary dysfunction was not affected by the extent of tumor removal. Radiotherapy did not increase the frequency of endocrine dysfunctions further. In conclusion, growth follow-up in childhood seems to be an important indicator of craniopharyngioma in early diagnosis. Radiotherapy and extent of tumor removal – either total or subtotal – did not influence endocrine outcome.

The Relationship Between Serum Adiponectin, Tumor Necrosis Factor-Alpha, Leptin Levels and Insulin Sensitivity in Childhood and Adolescent Obesity: Adiponectin is a Marker of Metabolic Syndrome

Objective: This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)−α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS). Methods: We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body−mass index (BMI) z−score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12−hour fast. Adiponectin, TNF−α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not. Results: Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF−α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI−z score, LDL, triglyceride, HOMA−IR, leptin and TNF−α as determinants of adiponectin revealed that BMI−z score was the only determinant for adiponectin (r:−0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=−0.23, p=0.005) in the groups of obese subjects. Mean serum adiponectin level in subjects with MS was lower than in subjects without MS (p=0.008). Conflict of interest:None declared.

Assessment of thyroid function during the long course of Hashimoto's thyroiditis in children and adolescents

Contextu2002 The prognosis of Hashimotos thyroiditis (HT) in children and adolescents is not well known and studies reporting long‐term outcome of the disease are scarce.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Significance Congenital adrenal hyperplasia resulting from mutations in the CYP11B1 gene, which encodes a steroidogenic enzyme 11β-hydroxylase, is a rare inherited disorder associated with hyperandrogenemia, short stature, hypertension, and virilization of female newborns. We present a comprehensive clinical, genetic, and hormonal characterization for 68 of 108 patients with a genotype from an International Consortium on Rare Steroid Disorders. We also use computational modeling to define the effect of each of the missense mutations on the structure of 11β-hydroxylase, information that can be used to predict clinical severity prenatally in high-risk mothers. Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

Cyclic pamidronate treatment in Bruck syndrome: Proposal of a new modality of treatment

In Bruck syndrome, patients have fragile bones and multiple fractures, as in OI, but bone fragility is associated with the unusual fi nding of pterygia and contractures of large joints. Typical radiological fi ndings are wormian bones in the skull, generalized osteopenia, bowing of long bones and multiple fractures, as in OI. Bruck syndrome can be distinguished from OI by the presence of clubfoot and congenital joint limitations and the absence of hearing loss and dentinogenesis imperfecta. Here we present the results of i.v. cyclic pamidronate treatment for bone fragility in a patient with Bruck syndrome. The same patient had been reported previously because a recessive mutation in PLOD2 gene was demonstrated, which is important for collagen cross-links. 2 While the patient was under pamidronate treatment for initial diagnosis of osteogenesis imperfecta, diagnosis of Bruck syndrome became defi nite. This is the only patient with Bruck syndrome reported in the literature who was treated with pamidronate for bone fragility.

Low cortisol levels in active juvenile idiopathic arthritis

The aim of our study was to evaluate the neuroendocrine system in patients with juvenile idiopathic arthritis (JIA) regarding the activity of disease. Twenty-one JIA patients (mean ageu2009±u2009standard deviation 10.5u2009±u20094.1xa0years) were included. None of the patients was taking steroids or antitumor necrosis factor-α therapy during this study. Ten healthy volunteers and ten volunteers with upper respiratory tract infection composed the control groups. Furthermore, ten of the 21 JIA patients were also evaluated during the remission period. Erythrocyte sedimentation rate, C-reactive protein, adrenocorticotropic hormone (ACTH), cortisol, prolactin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3, free T3, free T4, thyroid-stimulating hormone, interleukin-6 (IL-6) levels, and 24-h urinary cortisol were evaluated both during the active period and remission. The median levels of ACTH and cortisol at 08:00xa0a.m. were significantly lower in patients with active JIA than patients in remission period and the control groups (pu2009<u20090.05). Furthermore, the median level of urine cortisol in active JIA patients was significantly lower than remission period and control groups (pu2009<u20090.05). The median level of IGF-1 was significantly lower in active patients than that of remission (pu2009<u20090.05). The median level of IL-6 in active JIA patients was significantly higher than those in remission and control groups (pu2009<u20090.05). Our preliminary study suggested that impaired secretion of adenohypophyseal hormones and distorted bilateral interactions between the immune and endocrine systems in JIA. Further studies are needed to clarify the consequences of the impaired hormone secretion in JIA.

Novel and prevalent CYP11B1 gene mutations in Turkish patients with 11-β hydroxylase deficiency

11β-Hydroxylase deficiency is the second most frequent type of congenital adrenal hyperplasia and is more common in those of Turkish descent than in other populations. The purpose of this study is to examine the spectrum of CYP11B1 gene mutations in Turkish patients with 11β-hydroxylase deficiency. Twenty-eight patients from 24 families, ages ranging from 0.1 to 7 years, were included in the study. Clinical diagnosis was based on virilization and high levels of 11-deoxycortisol. Twenty-six cases exhibited the classical and 2 cases the non-classical form. Mutation screening of 9 CYP11B1 exons was performed by direct DNA sequence analysis, specifically amplifying CYP11B1 gene fragments while avoiding simultaneous amplification of homologous CYP11B2 gene sequences. Seventeen different mutations were detected, 6 of which are novel (p.Gln189Hisfs*70, p.Glu198Gly, p.Thr318Lys, p.Gly446Ser, IVS8+5G>C and exon 3-5 del). All of the identified mutations resulted in the classical form with severe virilization, except for the p.Gly446Ser mutation, which caused a late-onset type of 11β-hydroxylase deficiency. The c.954G>A;p.Thr318Thr mutation was the most common in our cohort, with an allele frequency of 14.6%.Of the CYP11B1 gene mutations detected, 75% were found in exons 3, 5 and 7 and the half of the mutations were nonsense, splice site, deletion or insertion mutations, causing severe virilization in female patients. The findings are important for genetic counseling and the prenatal diagnosis of Turkish patients with 11β-hydroxylase deficiency.

Assessment of gonadotrophin suppression in girls treated with GnRH analogue for central precocious puberty; validity of single luteinizing hormone measurement after leuprolide acetate injection

Objectiveu2002 Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic–pituitary–gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time‐consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90u2003min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut‐off level for LH indicating adequate suppression.

Evaluation of hypothalamic–pituitary function in children following acute bacterial meningitis

BackgroundPrevious studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis.MethodsPatients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis.ResultsPituitary function was assessed following a period of 8–135xa0months (mean 53xa0months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1xa0±xa04.4xa0years were included. Mean height SDS was 0.01xa0±xa01.07 and mean BMI SDS was 0.54xa0±xa01.15 all patients had a SDS above −2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8xa0%) had low IGF1 and IGFBP3 z-scores (<−2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10xa0ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia.ConclusionsOur findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.