Many new features have recently been incorporated to ÇEDD Çözüm/Child Metrics, an online and freely accessible scientific toolset. Various auxological assessments can now be made with data of children with genetic diseases (Prader Willi syndrome, Noonan syndrome, Turner syndrome, Down syndrome, and Achondroplasia) and preterm and term newborns. More detailed reports for height, weight, and body mass index data of a given child are now available. Last but not least, office and 24-hour ambulatory blood pressure values can be analyzed according to normative data.

The serum insulin-like growth factor-I (IGF-I) concentration is commonly used as a screening tool for growth hormone deficiency (GHD), but there is no consensus on the cut-off limit of IGF-I standard deviation score (SDS) to perform GH stimulation tests for confirmation or exclusion of GHD. We argue that the cut-off limit is dependent on the clinical pre-test likelihood of GHD and propose a diagnostic strategy in which the cut-off limit varies between zero to -2 SDS.

Objective: Studies examining changes in thyroid function in the course of chronic liver disease have mostly been conducted in adults. The aim of this study was to investigate thyroid dysfunction in children with chronic liver diseases.
Methods: Between 2005 and 2018, patients aged up to 18 years of age, diagnosed with chronic liver disease and had thyroid function test results available were included. Anthropometric characteristics, liver and thyroid function results were collected and analyzed.
Results: The study included 107 (53 female; 49.5%) patients aged between one month and 18 years-old. Of the 107 patients, 96 (89.7%) had normal thyroid function results, seven (6.5%) had subclinical hypothyroidism (SH) and four (3.7%) had euthyroid sick syndrome. Of the patients with SH, one (14.2%) had glycogen storage diasease, one (14.2%) had biliary atresia, one (14.2%) had undiagnosed cholestatic liver disease, one (14.2%) had Alagille syndrome, one (14.2%) had idiopatic hepatitis, one (14.2%) had progressive familial intra-hepatic cholestasis and one (14.2%) had congenital hepatic fibrosis. Spearman correlation analysis showed a negative correlation between free tri-iodothyronine and direct bilirubin (r=-0.329, p=0.027).
Conclusion: In conclusion, euthyroid sick syndrome or SH may affect up to 10% of children with chronic liver diseases. It is suggested that thyroid function should be evaluated in cases of pediatric chronic liver disease at diagnosis and during follow-up. Moreover, this study is the first to show a negative correlation between free T3 levels and direct bilirubin, suggesting a possible association between liver disease severity and thyroid function.

Objective: Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to imperfect treatment options.
Methods: Here we present nationwide initial and follow-up data on HR.
Results: From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed PHEX mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1st, 2nd and 3rd year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3rd year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group.
Conclusion: HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

Objective: To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA).
Methods: Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA.
Results: sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035).
Conclusion: sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.

Objective: Irisin is a recently discovered protein and is defined as an adipomyokine. The relation of irisin with carbohydrate metabolism and other hormone parameters have been investigated. However, studies evaluating the relationship between irisin and puberty are limited and inconclusive. The aim was to evaluate serum concentrations of irisin during different pubertal stages in male adolescents.
Methods: The study included normal weight pubertal male adolescents between the ages of 136/12-1411/12 who had entered puberty. Fasting serum irisin concentrations were evaluated, and bioelectrical impedance analysis was used to measure body fat ratio (BFR) and fat-free mass (FFM). BFR was also calculated by caliper measurement of subcutaneous fat at the triceps.
Results: Sixty-eight adolescents were enrolled. The number of adolescents in pubertal stage 2, 3, 4 and 5 were n=17 (25%), n=13 (19.1%), n=21 (30.1%) and n=17 (25%), respectively. The median values of the irisin are 8.80, 8.20, 9.15 and 7.24 ng/mL according to the 2-5 pubertal stages, respectively. The levels of circulating irisin did not differ according to the pubertal stage. Additionally, there was no significant relationship between irisin levels and body fat percentage or FFM.
Conclusion: Irisin levels do not differ after the onset of puberty or with progressing pubertal maturation. This study strengthens the evidence that there is no change in irisin concentration as puberty progresses. This may have important implications when using this adipomyokine in the future for diagnosis or treatment of obesity-related diseases.

Objective: Type 1 diabetes (T1D) is a disease characterized by severe insulin deficiency. In 2008 our group studied the prevalence of diabetes in adults between 20-80 years of age in Cyprus but data regarding this incidence in the pediatric population is lacking. The objective of this study was to report the incidence of T1D among permanent inhabitants aged 16 years or younger between 2001-2016 in Cyprus.
Methods: This study was a retrospective analysis. The patients were mainly evaluated and recorded at Dr. Burhan Nalbantoðlu Hospital, Nicosia. Data was also reviewed from Famagusta Government Hospital, Kyrenia Government Hospital, Near East University Hospital and the Cyprus Turkish Diabetes Association.
Results: A total of 107 subjects were diagnosed as T1D between 2001 and 2016 in the pediatric age group. Forty-nine (45.7%) were girls and 58 (54.3%) were boys. Of these 38.7% were resident in Nicosia, 30.2% Famagusta, 12.3% Kyrenia, 9.4% Guzelyurt and 7.5% Iskele. The proportion of newly diagnosed T1D was highest among children aged 9-12 years (35.5%) followed by children aged 5-8 years (32.7%). Newly diagnosed T1D most frequently presented in March and April. The overall mean incidence rate was 11.1/100,000 between 2001 and 2016. The incidence rates were similar and comparable among the years.
Conclusion: This study is the first to analyze the incidence of T1D in Cyprus. Compared to other countries the incidence rate is intermediate. Our findings are similar to the incidence rates of T1D in South Cyprus and Turkey.

Objective: Childhood obesity linked to metabolic alterations, tend to appear simultaneously with altered adipocytokines, suggesting a role in pathogenetic development. Low circulating level of total and high molecular weight (HMW) adiponectin have been associated with components of the metabolic syndrome (MetS) and could represent an independent risk factor with potential use as a biomarker. To examine the prevalence of MetS in Mexican school children and to investigate the association of total and HMW adiponectin levels with biochemical parameters related to MetS.
Methods: The study included a population of boys and girls, from 8 to 11 years old. Anthropometric and biochemical parameters were evaluated according to weight and MetS status. A correlation analysis was fitted to establish an association between adiponectin concentrations and metabolic indicators.
Results: One-hundred and fifty five children participated (59.4% females) from 8-11 years of age. The prevalence of MetS was of 10.3%. Impaired biochemical parameters, including total and HMW adiponectin, were associated with obesity. The adiponectin level was significantly lower in MetS than in non-MetS subjects (4.5 vs. 5.4 µg/mL). Total- but not HMW adiponectin concentration was negatively correlated with blood pressure, fasting insulin, fasting blood sugar and Homeostatic Model Assessment for Insulin Resistance.
Conclusion: In young children, the total adiponectin level is associated with impaired biochemical parameters of carbohydrate metabolism and could be an excellent early predictor of metabolic complications.

Objective: Despite the guidelines, significant variations can be encountered in initial therapy for pediatric diabetic ketoacidosis (DKA) in the prehospital setting. These variations occur mostly in fluid administration, insulin dosing, route of administration, and other aspects of the initial resuscitation and stabilization. The aim was to identify the effect of transport care on outcomes in children with DKA admitted to the emergency department (ED).
Methods: Patients admitted to a tertiary-care pediatric ED between 2015-2019 with a diagnosis of DKA were retrospectively identified. Details of pre-pediatric ED care, including transport modality, patient demographics, clinical features, laboratory evaluation, fluid therapy, insulin dosing, and short-term outcome were recorded.
Results: The study cohort included 147 episodes of DKA in 136 patients aged 9 months-21 years. Emergency Medical Service (EMS) transported only 37.4% of cases. EMS utilization rate was significantly higher (p=0.003) in severe cases, most of whom were >10 years (p=0.04). During transport 85% received intravenous fluid bolus. Use of fluids other than normal saline was significantly higher when transport time was >30 minutes (p=0.001). Acute kidney injury and cerebral edema developed in 21.7% and 7.4% of episodes, respectively. These complications were more common in the EMS transport group. Pediatric intensive care admission rate was also higher in the EMS compared to the non-EMS group (p=0.01)
Conclusion: Parents did not call the ambulance for most cases although a higher complication rate occurred in EMS patients. EMS providers and referral facilities should improve their knowledge of pediatric DKA.

Objective: Soluble CD40 ligand (sCD40L) is elevated in various autoimmune disorders, which may have diagnostic and therapeutic implications. The aims of the current study were to evaluate serum sCD40L concentrations in children with newly diagnosed Graves’ disease (GD) and to correlate its levels with patients’ clinical and laboratory parameters.
Methods: This study included 48 children with newly diagnosed GD and 48 healthy children. Serum thyroid-stimulating hormone (TSH) (TSH, fT4 and fT3), TSH receptor antibodies (TRAbs), high sensitivity C-reactive protein (hsCRP) and sCD40L levels and thyroid volume were measured.
Results: Compared to control subjects, children with GD had higher thyroid volume standard deviation scores (SDS) (p=0.001), and higher levels of hsCRP (p=0.001), TRAbs (p=0.001) and sCD40L (p=0.001). Significant correlations were found between sCD40L and age (p=0.01), thyroid volume SDS (p=0.001), hsCRP (p=0.01) and TRAbs (p=0.001). In multivariate analysis, sCD40L concentrations were correlated with TRAbs [odds ratio (OR)=3.1, 95% confidence intervals (CI): 2.2-2.7, p=0.001] and thyroid volume SDS (OR=2.1, 95% CI: 1.2-2.7, p=0.001).
Conclusion: This preliminary study has evidence of high concentrations of sCD40L in children with newly diagnosed GD and a correlation between sCD40L and both TRAbs and thyroid volume, which may indicate a biologically active role for sCD40L in the pathogenesis of GD.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. The clinical presentation of pediatric PPGLs is highly variable. In cases with pheochromocytoma (PCC), excess catecholamine may stimulate myocytes and cause structural changes, leading to life-threatening complications ranging from stress cardiomyopathy (CM) to dilated CM. Herein, we report the case of catecholamine-induced myocarditis in a child with asymptomatic PCC. A 12-year-and-2-month-old male patient with a known diagnosis of type-1 neurofibromatosis was brought to the emergency department due to palpitations and vomiting. On physical examination, arterial blood pressure was 113/81 mmHg, pulse was 125/min, and body temperature was 36.5 °C. Laboratory tests showed a leucocyte count of 12.8x103 µL/L and a serum C-reactive protein level of 1.1 mg/dL (Normal range: 0-0.5). Thyroid function tests were normal, while cardiac enzymes were elevated. Electrocardiogram revealed no pathological findings other than sinus tachycardia. The patient was diagnosed with and treated for myocarditis as echocardiography revealed a left ventricular ejection fraction of 48%. Viral and bacterial agents that may cause myocarditis were excluded via serological tests and blood cultures. Blood pressure, normal at the time of admission, was elevated (140/90 mmHg) on the 5th day of hospitalization. Magnetic resonance imaging revealed a 41x46x45 mm solid adrenal mass. The diagnosis of PCC was confirmed by elevated urinary and plasma metanephrines. The patient underwent surgery. Histopathology of the excised mass was compatible with PCC. It should be kept in mind that, even if there are no signs and symptoms of catecholamine elevation, CM may be the first sign of PCC.

Adrenal hypoplasia is a rare congenital disorder. In spite of biochemical and molecular genetic evaluation, etiology in many patients with adrenal hypoplasia is not clear. MIRAGE syndrome is a recently recognized congenital disorder characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Here we present a case of MIRAGE syndrome due to a heterozygous missense variant (c.2920G>A; p.E974K) mutation in the sterile alpha motif domain-containing protein-9 (SAMD9) gene. This report describes the first MIRAGE syndrome patient in Turkey.

Pituitary stalk interruption syndrome (PSIS) is characterized by the association of an absent or thin pituitary stalk, an absent or hypoplastic anterior pituitary lobe and an ectopic posterior pituitary (EPP) lobe. The causes of this anatomical defect include both genetic and environmental factors. Molecular genetic defects have been indentified in a small number of patients with PSIS. A 4-year-old boy presented with hypoglycemia and hyponatremia associated with growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone deficiencies. The patient had right sided strabismus. magnetic resonance imaging images showed pituitary hypoplasia, EPP and absent pituitary stalk. A novel Receptor Roundabout-1 (ROBO1) missense mutation (c.1690C>T, p.Pro564Ser) that may contribute to the disorder was found in this patient and his mother, who also exhibited pituitary abnormalities.

Loss-of-function mutations of IGSF1 are an X-linked cause of central hypothyroidism (CeH) and hypoprolactinemia. A boy who is now 15.2 years old presented at the age of 7.69 years for evaluation of obesity. Previous thyroid function evaluation suggested CeH [FT4 0.6 ng/mL, thyroid-stimulating hormone (TSH) 2.2 mIU/L] but his physician took no action. At presentation he was clinically and biochemically euthyroid, prepubertal and obese. Serum prolactin (PRL) was undetectable. Biochemistry was normal except for mild hypercholesterolemia, total cholesterol 198 mg/dL. Subsequently FT4 and TSH levels fluctuated between 0.72-0.95 ng/dL (normal 0.8-2.0) and 1.94-5.77 mIU/L (normal 0.3-5.0), respectively. Sequencing of IGSF1 gene revealed a novel genetic change c.3805C>T in exon 19; substitution of amino acid Arginine at position 1269 with a premature «stop» codon resulting in an altered protein product. The patient additionally presented delayed adrenarche, low height velocity that resolved spontaneously and normal pubertal onset associated with increased FSH levels. At 14 years-of-age, while the patient was at Tanner stage 4, PRL levels became detectable, rising gradually to 2.3 ng/mL at last examination. Thyroxine replacement therapy resulted in decrease in total cholesterol 103 mg/dL. A high index of suspicion for the disorder is needed since several measurements of thyroid function may be required for CeH to be disclosed. The patient’s normal FT4 levels and normal intelligence would have resulted in a missed diagnosis if the serum PRL levels had not been measured. This case highlights the importance of measuring PRL in a boy with low normal FT4 and normal TSH levels.