Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

The Growth Characteristics of Patients with Noonan Syndrome: Results of Three Years of Growth Hormone Treatment: A Nationwide Multicenter Study.

OBJECTIVE: Noonan syndrome (NS) is a multisystem disorder, and short stature is its most striking manifestation. Optimal growth hormone (GH) treatment for NS is still controversial. In this study, using a nationwide registration system, we aimed to evaluate the growth characteristics and the clinical features of NS patients in Turkey and their growth response to GH treatment. METHODS: Children and adolescents with a diagnosis of NS were included inthe study. Laboratory assessment including standard GH stimulation test results were evaluated. Height increment of patients with or without GH treatment were analyzed after three years of therapy. RESULTS: A total of 124 NS patients from different centers were entered in the web-based system. Short stature and typical face appearance were the most frequently encountered diagnostic features of our patients. Of the 84 patients who were followed long-term, 47 hadreceived recombinant human GH (rhGH). In this group of 47 patients, height standard deviation score (HSDS) increased from -3.62±1.14 to -2.85±0.96 after three years of therapy, indicating significant differences from the patients who did not receive GH treatment. PTPN11 gene was analyzed in 61 patients, and 64% of these patients were found to have a mutation. HSDS at admission was similar in patients with or without PTPN11 gene mutation. CONCLUSION: A diagnosis of NS should be kept in mind in all patients with short stature showing systemic clinical findings. GH therapy is effective for improvement of short stature especially in the first two years of treatment. Further studies are needed for optimisation of GH therapy and evaluation of final height data in NS patients.

Role of circulating adipocytokines vaspin, apelin, and visfatin in the loss of appetite in underweight children: a pilot trial.

OBJECTIVES: To investigate serum concentrations of vaspin, apelin, and visfatin in underweight children and their association with anthropometric and nutritional markers of malnutrition. SUBJECTS AND METHODS: We recruited 44 underweight prepubertal children (youngest age = 2 years) with thinness grades of 1, 2, and 3, and body weights < 90% of ideal body weight due to loss of appetite and less frequent hunger episodes. Forty-one healthy age- and gender-matched controls were also included in the study. Serum fasting vaspin, apelin, and visfatin concentrations were measured by enzyme immunoassay technique. RESULTS: Mean vaspin and apelin levels were significantly lower in underweight children compared to controls (vaspin: 0.44 ± 0.18 vs. 0.58 ± 0.35 pg/mL, p = 0.024; apelin: 483.37 ± 333.26 vs. 711.71 ± 616.50 pg/mL, p = 0.041). Visfatin levels were lower in underweight children compared to controls, but the values were not statistically significant (177.81 ± 158.01 vs. 221.15 ± 212.94 pg/mL, p = 0.119). CONCLUSIONS: In underweight children, decreased vaspin and apelin levels should be considered in the etiology of anorexia.

Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey.

OBJECTIVE: Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey. METHODS: A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers. RESULTS: Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height. CONCLUSION: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Association between the corrected QT interval and carotid artery intima-media thickness in obese children.

OBJECTIVE: Sudden death has been reported in asymptomatic obese adults and the mechanism is unclear. In recent years, obesity has shown a dramatic increase in children and this enhances the risk factors for the development of cardiovascular disease. The aim of this study was to investigate whether there is repolarization abnormality and any potential risk factor such as increase in intima-media thickness (IMT) of carotid artery for corrected QT (QTc) prolongation among obese children. METHODS: A total of 60 obese children, 30 of which had features of metabolic syndrome (MS), and 23 age-matched controls were included in the study. QTc interval was calculated at rest. The IMT of both common carotid arteries (CCA) was measured. The relationship between QTc, IMT of right and left CCA and insulin sensitivity indices were evaluated in the study group. RESULTS: The QTc interval of the children with simple exogenous obesity (SEO) were longer than in the controls (p=0.024). The IMT of both carotid arteries of the obese girls and boys with and without MS were higher than the controls (p=<0.001). The QTc was significantly affected by the parameters pertaining to the right carotid artery IMT, to chronologic age and HDL-C. CONCLUSION: Since obesity may cause subclinical atherosclerotic disease regardless of sex, obese children must be followed closely for early cardiovascular problems.

The effect of insulin resistance and obesity on low-density lipoprotein particle size in children.

OBJECTIVE: In adults, it was shown that obesity and insulin resistance affect low-density lipoprotein (LDL) particle size and small dense (sd) LDL is associated with cardiovascular diseases. In this study, we investigated the effect of obesity and insulin resistance on LDL particle size. METHODS: Twenty-six obese children (13 girls, 13 boys) with a median age of 10.5 years and 27 healthy control subjects (17 girls, 10 boys) with a median age of 11.5 were enrolled in the study. RESULTS: The number of patients with insulin resistance in the obese group was 15 out of 26. In the control group, there was no subject with insulin resistance. Serum triglyceride and very LDL (VLDL) levels were higher and serum high-density lipoprotein levels (HDL) were lower in the obese patients than in the controls. There was no statistical difference in the LDL particle size between the two groups (medians: 26.6 vs. 26.7 nm (p=0.575)). The size of LDL particle was not correlated with body mass index (BMI) standard deviation score (SDS), homeostasis model assessment of insulin resistance (HOMA-IR), or serum lipids. CONCLUSION: Measurement of LDL particle size as a routine procedure is not necessary in childhood obesity.

Adiponectin and resistin concentrations after glucose load in adolescents with polycystic ovary syndrome.

Our aims were to evaluate the serum adiponectin and resistin levels at fasting and after glucose load and their interaction with risk of cardiovascular disease (CVD) in adolescents with polycystic ovary syndrome (PCOS). Twenty-two adolescents with PCOS and 16 healthy controls were included in the study. Oral glucose tolerance test (OGTT) was performed in all adolescents. Fasting lipids was measured. Insulin, glucose, adiponectin, and resistin levels were measured at 0 and 120 min of OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and the whole -body insulin sensitivity index (ISI) were calculated. Fasting adiponectin was correlated with ISI (r = 0.729, p < 0.0001), FGIR (r = 0.696, p < 0.0001), QUICKI (r = 0.592, p = 0.004) and HDL-C (r = 0.516, p = 0.028), systolic blood pressure (r = -0.732, p < 0.0001), body mass index (r = -0.738, p < 0.0001), waist circumference (r = -0.706, p < 0.0001), and HOMA-IR (r = -0.595, p = 0.003). No correlation was found between resistin and insulin resistance indexes. Obese adolescents with PCOS have increased CVD risk such as dyslipidemia, hypertension, and insulin resistance than normo-weight PCOS. Hypoadiponectinaemia could be increase risks levels in obese girls with PCOS.

Precocious puberty in a girl with Down syndrome due to primary hypothyroidism.

Van Wyk-Grumbach syndrome is a rare cause of precocious puberty due to hypothyroidism. We report a case of Van Wyk-Grumbach syndrome in a 4.3-year-old female patient with Down syndrome. She was investigated for hematuria for three months before she was referred to our clinic. Physical examination revealed typical morphologic features of Down syndrome and hypothyroidism. Pubertal development stages were: breast at stage III and pubic hair at stage I. In luteinizing hormone releasing hormone (LHRH) stimulation test, peak LH level remained less than 0.1 mIU/ml. Serum estradiol level was 117.7 pg/ml, which was higher than normal for her age (normal range: 2-15 pg/ml). The pelvic ultrasonographic evaluation revealed bilateral multicystic enlarged ovaries. Serum thyroid stimulating hormone (TSH) concentration was higher than 500 microIU/ml and free thyroxin (FT4) and free triiodothyronine (FT3) levels were as low as 0.4 ng/dl (0.7-1.48) and 1.0 pg/ml (1.71-3.71), respectively. L-thyroxin treatment at a dose of 100 microg/m2/day was started. Regression in breast development was obtained after one month and her bleeding did not repeat again. In conclusion, urinary and vaginal bleeding in young children must be clearly differentiated, and hypothyroidism must be investigated in children who have precocious puberty.

Acromegaly symptoms without pituitary adenoma in an adolescent.

The diagnosis of acromegaly requires a glucose-suppressed growth hormone (GH) nadir greater than 1 microg/l associated with clinical symptoms and signs. Here, we present a patient who has acromegalic clinical findings associated with a nadir GH level < 1 microg/l during an oral glucose tolerance test.

Protein Z and natural anticoagulants in children on peritoneal dialysis and hemodialysis.

Hemostatic alterations due to abnormalities in the coagulation and fibrinolytic system may occur in dialysis patients. Protein Z (PZ) is a vitamin K-dependent coagulation protein promoting assembly of thrombin with phospholipid vesicles. The aim of this study was to investigate PZ and natural anticoagulants in children on hemodialysis (HD) and peritoneal dialysis (PD). Protein Z, protein C (PC), protein S (PS), antithrombin III (AT III), and fibrinogen levels were studied in 24 PD, 13 HD patients and 23 controls. Plasma PZ levels in patients on HD were significantly higher than those on PD and control group (p = 0.04, p = 0.03). We observed elevated PC, PS and AT III activities in children on PD when compared to controls (p = 0.011, p = 0.003, p < 0.001). In HD patients, only PS activity was increased compared to controls (p = 0.016). PC and PS activities did not differ between PD and HD patients whereas AT III activity was higher in PD patients compared to HD patients (p < 0.001). Normal/high levels of PC, PS and AT III suggest that children on PD or HD treatment do not seem to have an increased risk of thrombogenesis due to reduction of these proteins. Increased PZ levels, however, might contribute to the hemostatic alterations in children on HD treatment along with other well known abnormalities.

Cushing's syndrome and adrenocortical insufficiency caused by topical steroids: misuse or abuse?

BACKGROUND: Prolonged application of topical steroids transiently suppresses the hypothalamic-pituitary-adrenal axis (HPA). Infants who are exposed to topical corticosteroids have greater risk for Cushing's syndrome or adrenocortical insufficiency caused by suppression of the HPA axis because glucocorticoids are highly absorbed through the diaper area. Here, we report six infants (four girls, two boys) aged between 3 and 8 months who were exposed to potent topical corticosteroids (clobetasol propionate and diflucortolone valerate) by the mother's application without prescription. METHODS: We examined the HPA axis and other side effects of the potent glucocorticoid therapy in these infants. After stopping the topical corticosteroid, serum AST, ALT, lipids, morning cortisol and ACTH levels were measured. A low dose ACTH stimulation test was carried out. Hydrocortisone was started for the prevention of glucocorticoid withdrawal syndrome and the dose was gradually decreased. Abdominal ultrasonography was performed to investigate hepatosteatosis. RESULTS: The ACTH stimulation test showed suppression of the HPA axis in these infants. Hepatomegaly was found in all infants and three of them had hepatosteatosis. Liver transaminase levels were elevated in five infants. Five patients have been followed for 6-14 months. One infant died due to generalized Cytomegalovirus infection. CONCLUSION: We emphasize that physicians should be alert for the dangerous side-effects of topical steroids and they should avoid long-term use. Furthermore, parents should be informed about the side-effects when topical steroid treatment is chosen.