Nurgun Kandemir

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.

Significance of Low-Dose and Standard-Dose ACTH Tests Compared to Overnight Metyrapone Test in the Diagnosis of Adrenal Insufficiency in Childhood

Objective: To discover the value of low-dose (LDAT) and standard-dose ACTH tests (SDAT) as compared with the metyrapone test in the diagnosis of secondary adrenal insufficiency. Patients and Methods: LDAT (0.5 µg/m2), SDAT (250 µg/m2) and overnight metyrapone (30 mg/kg) tests were carried out in 29 patients with suspected adrenal insufficiency. LDAT and SDAT were also performed in 36 control subjects. Results: 18 of 29 patients were grouped in the adrenal-sufficient (AS) group and 11 of 29 patients in the adrenal-deficient (AD) group according to the metyrapone test results. The control group had significantly higher cortisol responses than the AS and AD groups during LDAT. The control group had similar cortisol responses to the AS group but higher cortisol responses than the AD group during SDAT. The AS group was divided into 2 subgroups: AS patients with multiple pituitary hormone deficiencies (AS-multiple) and AS patients with idiopathic growth hormone deficiencies (AS-isolated). The AS-multiple group had statistically lower cortisol responses than the control group during LDAT. Receiver-operating characteristics analysis revealed that the cortisol cutoff value in LDAT was 19.8 µg/dl (100% sensitivity, 89% specificity) and 30.4 µg/dl in SDAT (82% sensitivity, 78% specificity). Conclusion: LDAT is capable of identifying patients with adrenal insufficiency more effectively than SDAT. The cortisol cutoff value in LDAT was calculated as 19.8 µg/dl with 100% sensitivity. AS patients with multiple pituitary hormone deficiencies had lower cortisol responses to LDAT than the control group implying that these patients might have a lower cortisol secretory capacity than healthy subjects.

Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism.

Objectives Multisystem pseudohypoaldosteronism (PHA) is a rare autosomal recessive aldosterone unresponsiveness syndrome that results from mutations in the genes encoding epithelial sodium channel (ENaC) subunits α, β and γ. In this study we examined three PHA patients to identify mutations responsible for PHA with different clinical presentations.

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.

Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: Clinical and radiographic delineation of a pleiotropic disorder

Enchondromas are a feature of several constitutional disorders of bone, and the classification of different nosologic entities is still provisional. Among these disorders, spondyloenchondrodysplasia (SPENCD), as outlined by Schorr et al. [ 1976 ], is defined by the presence of radiolucent spondylar and metaphyseal lesions that represent persistence of islands of chondroid tissue within bone. Careful review of radiographic findings is needed to distinguish SPENCD from the many other disorders combining enchondromas with spinal lesions. Even when strict criteria are applied, it appears that SPENCD is clinically heterogeneous, as some SPENCD patients are neurologically intact while others present with spasticity, mental retardation, and cerebral calcifications in different combinations, and it has been suggested that SPENCD should be divided in two types. We herein report ten individuals from six families with SPENCD and illustrate the radiographic changes. Seven individuals had CNS manifestations including spasticity, developmental delay, and late‐onset cerebral calcifications. We also noted that six individuals had clinical manifestations of autoimmunity (auto‐immune thrombocytopenic purpura, auto‐immune hemolytic anemia, auto‐immune thyroiditis, and SLE) and one had been diagnosed with immune deficiency. Neurological and autoimmune manifestations were seen in different combinations within one single family. These observations suggest that SPENCD may be a single entity defined by specific radiographic features, but with remarkably pleiotropic manifestations that include CNS disease (spasticity, mental retardation, and calcifications), as well as immune dysregulation ranging from autoimmunity to immunodeficiency. The notion of recessive inheritance hitherto assumed is challenged by the observation of two apparently dominant pedigrees.

Screening for congenital hypothyroidism in Turkey

AbstractA pilot study was performed to determine the incidence of congenital hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From December 1991 to December 1992, 30097 newborns were screened for CH using a primary measurement of thyroid stimulating hormone in capillary blood on days 3–5 of life. Samples were obtained in collaboration with the ongoing nationwide phenylketonuria screening programme. Eleven cases of primary CH were detected giving the incidence of 1∶2736. Recall rate was 2.3%. Replacement therapy withl-thyroxine was started after the confirmation of diagnosis. The median age at the initiation of replacement therapy was 23 days (range 7–35 days).ConclusionThe incidence of CH is notably higher in Turkey than reported in most other countries. Iodine deficiency and/or dyshormonogenesis might contribute to this high incidence. This result emphasizes the necessity of a nationwide screening programme.

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.

Thyroid involvement in Langerhans cell histiocytosis: a report of two cases and review of the literature

Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and pathogenesis characterized by abnormal clonal proliferation and accumulation of antigen presenting Langerhans cells at various tissues and organs. Almost all organs or systems may be involved, and the prognosis depends on the involved sites and the presence of organ dysfunction. Thyroid tissue is a rarely affected site in children, and without histopathological evaluation it may be difficult to distinguish from other thyroid disorders because of the similar physical examination, laboratory and imaging findings. Here we report on two patients with histopathologically proven thyroid involvement of LCH. Additionally, the differential diagnosis of diffusely enlarged or multinodular thyroid glands in children is discussed, and a review of the literature of thyroid involvement in LCH is given. In the differential diagnosis of enlarged thyroid glands, especially in the presence of other endocrinological manifestations, LCH must be taken into consideration.

Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use

AbstractThe possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264xa0μg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0–11 and ≥12xa0years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15xa0μg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9xa0%) participants underwent LDAT, and seven (7.7, 95xa0% CI 3.5–15.3xa0%) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8xa0%, pu2009=u20090.009). Use of ICS at moderate-to-high doses for at least 7xa0months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22xa0μg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95xa0% confidence interval (CI) 1.23–42.26, pu2009=u20090.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291xa0μg/day FP (area under the curve (AUC)u2009=u20090.840, pu2009=u20090.003) for predicting HPA-ASn Conclusion: The prevalence of HPA-AS was found to be 7.7xa0% in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS.What is Known:• Inhaled corticosteroids are the current mainstay treatment for persistent asthma.• The possible risk of systemic side effects due to regular consumption of inhaled corticosteroids (ICS) is a frequent issue of concern for both physicians and parents of patients in the pediatric age group.What is New:• The prevalence of hypothalamic-pituitary-adrenal axis suppression was 7.7xa0% in a group of children taking inhaled corticosteroids not only at high but also at moderate doses.• Among the duration, type, and dose of inhaled corticosteroids, only the use of fluticasone propionate equivalent metered-dose inhaler at a body mass index-adjusted daily dose of ≥22xa0μg was found to increase the risk for hypothalamic-pituitary-adrenal axis suppression.