Genotype-phenotype characteristics of 57 patients with Prader-Willi syndrome: a single-center experience from Turkey.

OBJECTIVES: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by the loss of expression of the paternal copy of the imprinted genes on chromosome 15q11-q13. A variety of findings have been reported on the phenotypic differences between the genetic subtypes of PWS. This article compares the clinical findings of 57 PWS patients by genetic subtype and explores possible associations in this context. METHODS: Methylation­specific multiplex ligation-dependent probe amplification and single nucleotide polymorphism microarrays were used to diagnose deletion and uniparental disomy (UPD). For phenotype-genotype correlation, clinical data were collected and genetic subgroups were compared statistically, and P < 0.05 was considered to indicate statistical significance. RESULTS: These 57 patients consisted of 15 type I deletions, 20 type II deletions, six atypic deletions, 11 heterodisomy UPD, four isodisomy UPD, and one translocation-type PWS. All patients had hypotonia, poor neonatal sucking, and feeding difficulties during infancy. Other PWS-related clinical findings, such as speech articulation problems (85.9%), sleep apnea (77.2%), normal birth length (71.9%), small hands/feet (71.9%), childhood polyphagia (57.9%), clinodactyly (56.1%), thick viscous saliva (54.4%), and behavioral problems (50.9%) were observed at varying rates with no statistical difference between genetic subtypes in general. CONCLUSION: This study highlights the phenotype-genotype associations on PWS from a cohort of Turkish pediatric patients as a single-center experience.

Does metabolic control of the disease related with bone turnover markers in children with type 1 diabetes mellitus in Turkey?

BACKGROUND: The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes. MATERIALS AND METHODS: The children were divided into two groups according to their glycated hemoglobin (HbA1c) (%) levels: a group with HbA1c levels < 8% (n = 16) and: a group with HbA1c levels > 8% (n = 18). The serum total oxidative status (TOS) (µmol/L), total antioxidant status (TAS) (mmol/L), alkaline phosphatase (ALP) (IU/L), osteocalcin (OC) (ng/ml), procollagen type-1-N-terminal peptide (P1NP) (ng/ml), and vitamin D (IU) levels and food consumption frequencies were determined. RESULTS: When patients were classified according to HbA1c (%) levels, those with HbA1c levels < 8% were found to have lower TOS (µmol/L) values (8.7 ± 6.16, 9.5 ± 5.60) and higher serum OC (ng/mL) (24.2 ± 16.92, 22.0 ± 6.21) levels than those with HbA1c levels > 8% (p < 0.05). Regardless of the level of metabolic control, there was a statistically significant association between serum TOS (µmol/L) and P1NP (ng/ml) (p < 0.05) levels, with no group-specific relationship (HbA1c levels <%8 or HbA1c levels >%8). CONCLUSION: HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes.

Transient Neonatal Diabetes Mellitus and Seizure with an Unknown Etiology.

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes, usually occurring in the first 6 months of life. Here, we present a newborn, which was admitted with epileptic seizure on the postnatal second day of life. Sepsis and meningitis were ruled out. Cranial imaging and electroencephalography revealed normal. She developed transient NDM on the follow-up and was diagnosed to carry an ABCC8 mutation. Although the neurological features are more common in patients with KCJN11 mutations, patients with ABCC8 mutations could also represent with subtle neurodevelopmental changes or even with epileptic seizures. The genetic testing and appropriate therapy is important in this patient group for predicting clinical course and possible additional features.

The Relationship Between Premature Adrenarche and Platelet Aggregation

Objective: Premature adrenarche (PA) has been associated with an increase in adrenal androgens, and the hyperandrogenic hormonal environment is known to lead to increased platelet (PLT) aggregation. Here, we evaluated the effects of PA on PLT aggregation in PLT-rich plasma samples from female patients. Methods: The study included 40 female patients diagnosed with PA between February, 2014 and June, 2018 and 30 healthy female individuals as a control group. Adenosine diphosphate (ADP) and collagen-induced PLT aggregation were studied via the photometric aggregometry method. Results: There were no significant differences in the PLT count or volume values between those participants with PA and the control group. Additionally, the ADP-induced maximum aggregation time, value, and slope values did not significantly differ between the patient and control groups (p>0.05). However, the collagen-induced maximum aggregation time, value, and slope values were significantly higher in the studygroup (p<0.001). Conclusion: Increased collagen-induced PLT aggregation was detected in female patients with PA. As PA is associated with a higher risk of cardiovascular events later in life, close follow-up of PA in this respect may be beneficial.

Evaluation of the nutritional status of children with type 1 diabetes and their healthy siblings.

BACKGROUND: Although there are studies evaluating the psychological adjustment of healthy children when their siblings have type 1 diabetes mellitus (T1DM), no study evaluating their nutritional status exists. Thus, this study aimed to determine the nutritional status of children with T1DM and their healthy siblings. MATERIAL AND METHODS: Data from a control group, healthy siblings, and patients who were followed and treated for T1D in the Paediatric Gastroenterology and Paediatric Endocrinology outpatient clinics of the Health Sciences University Gülhane Medical Faculty between November 2019 and November 2020 were analysed and compared. The groups were compared in terms of nutritional characteristics, daily macro and micronutrient intakes and classified according to their body mass index (BMI) Z-scores. RESULTS: The study population consisted of 29 children with T1DM (51.7% female, 48.3% male; age: 11.00 ±3.66 years), 36 healthy siblings of children with T1D (50% female, 50% male; age: 9.61 ±4.84 years), and a control group of 58 healthy children (51.7% female, 48.3% male; age: 10.68 ±3.01years).The BMI Z-score of 28.6%of healthy siblings and 25% of children with T1D was > 1 SD or overweight. All of the control group children were of normal weight. None of the children were obese; however, the overweight rate was significantly higher in the healthy siblings and diabetes groups compared to the control group (p = 0.012). Daily energy intake (%) was significantly higher in the control group than in the healthy siblings (p < 0.001). CONCLUSIONS: A quarter of the children with T1D over five years of age were overweight. In addition, healthy siblings were found to have higher BMI Z-scores than controls. This is the first study to evaluate the nutritional status of siblings of patients with T1D and will hopefully lead to more comprehensive studies that will also assess their daily exercise and physical activity.

Mosquito hypersensitivity may be associated with atopic background in children.

BACKGROUND: Many children encounter unusual or "exaggerated" reactions such as large local, atypical or systemic reactions after mosquito bites. OBJECTIVE: The aim of this study was to document the clinical features of children with mosquito allergy and investigate the possible associations between demographic features and type of reactions in this population. METHODS: Children with large local or unusual reactions after mosquito bites who attended to our outpatient pediatric allergy department were enrolled in the study along with control subjects. RESULTS: A total of 180 children (94 with mosquito allergy and 86 age and sex-matched control subjects) with a median age of 6.8 years (IQR 5.5-9.3) were enrolled. Atopy (35.1% vs. 11.6%, p < 0.001) and grass pollen sensitization (28.7% vs. 8.1%, p < 0.001) were significantly more frequent in children with mosquito allergy. Skin prick test with mosquito allergen was positive in only 6 children (6,4%). Grass pollen sensitization was most common in children (28.7%) followed by sensitization to house dust mite (9.6%). 30 children (31.9%) had an accompanying atopic disease such as allergic rhinitis, asthma or atopic dermatitis. Bullae were significantly more frequent in children with asthma (41.7% vs.15.9, p = 0.034). The median duration of symptoms after onset were significantly longer in patients with ecchymosis, with immediate wheals and in children whose symptoms start in 20 min to 4 hours after mosquito bites. CONCLUSION: There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background.

Mosquito hypersensitivity may be associated with atopic background in children

Background Many children encounter unusual or “exaggerated” reactions such as large local, atypical or systemic reactions after mosquito bites. Objective The aim of this study was to document the clinical features of children with mosquito allergy and investigate the possible associations between demographic features and type of reactions in this population. Methods Children with large local or unusual reactions after mosquito bites who attended to our outpatient pediatric allergy department were enrolled in the study along with control subjects. Results A total of 180 children (94 with mosquito allergy and 86 age and sex-matched control subjects) with a median age of 6.8 years (IQR 5.5–9.3) were enrolled. Atopy (35.1% vs. 11.6%, p < 0.001) and grass pollen sensitization (28.7% vs. 8.1%, p < 0.001) were significantly more frequent in children with mosquito allergy. Skin prick test with mosquito allergen was positive in only 6 children (6,4%). Grass pollen sensitization was most common in children (28.7%) followed by sensitization to house dust mite (9.6%). 30 children (31.9%) had an accompanying atopic disease such as allergic rhinitis, asthma or atopic dermatitis. Bullae were significantly more frequent in children with asthma (41.7% vs.15.9, p = 0.034). The median duration of symptoms after onset were significantly longer in patients with ecchymosis, with immediate wheals and in children whose symptoms start in 20 min to 4 hours after mosquito bites. Conclusion There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background (AU)

Children's Power of Food Scale: Turkish validity and reliability study.

OBJECTIVE: The aim of the present study was to validate the Turkish version of the Children's Power of Food Scale (C-PFS-T) after translation of the original version. DESIGN: The data were collected via face-to-face interviews using the C-PFS-T and a socio-demographic information form. BMI was calculated by dividing body weight by the square of the height. After the adaptation of the scale to Turkish language, validity and reliability analysis were conducted for the C-PFS-T. SETTING: Gülhane Training and Research Hospital Department of Child Health and Diseases Nutrition and Diet Unit in Ankara. PARTICIPANTS: This research was conducted with volunteer children and adolescents between the ages of 9 and 16 years (n 268). RESULTS: It was concluded that the 15-item C-PFS-T was collected under three factors as in the original version of the child version. Cronbach's α coefficient was found to be 0·878 for the scale. The confirmatory factor analysis results showed the acceptability and applicability of adapting the version of the C-PFS-T in terms of χ2/df (= 3·816), adjusted goodness-of-fit index (AGFI = 0·931), root mean square error of approximation (RMSEA = 0·082) and goodness-of-fit index (GFI = 0·852) fit indices. C-PFS-T total score's median value of obese group wasn't substantially different from normal weight group.Conclusions:It was concluded that the Turkish version of the C-PFS, which provides an assessment of the hedonic hunger status of children and adolescents with fifteen items and threesubdimensions, has sufficient reliability and validity to be applied to these subjects.

Sleep disordered breathing in patients with Prader willi syndrome: Impact of underlying genetic mechanism.

INTRODUCTION: Sleep-disordered breathing (SDB) is common in children with PWS. In the current study, we aimed to evaluate the severity of SDB in patients with PWS using polysomnography (PSG), and assess the effect of the underlying genetic mechanism on PSG parameters. METHODS: Children with PWS, referred to our sleep laboratory between March 2016 and January 2020 were enrolled. PSG parameters, demographic data, body mass index (BMI), and symptoms related to SDB were recorded. The effect of non-invasive ventilation strategies and the outcome of therapy on PSG parameters were evaluated. RESULTS: In our study, 64.5% of the patients had severe sleep apnea syndrome (total apnea hypopnea index (AHI) ≥10 events/hour). 22.6% had significantly high (>5 events/hour) central sleep apnea. Patients with a deletion had significantly lower initial and mean SaO2, longer sleep time SaO2 under 90%, oxygen desaturation % and total AHI when compared to those with uniparental disomy. PSG parameters were similar between patients who did or didn't receive growth hormone treatment. CONCLUSION: The majority of the PWS patients had severe sleep apnea syndrome characterized mainly by hypopneas which were accompanied by central apneas. There was a more severe impact on oxygen parameters and total AHI in patients with deletions.

Evaluation of the resilience of the girls with central precocious puberty treated with gonadotropin-releasing hormone analog.

OBJECTIVES: The aim of this study was to evaluate the resilience of girls with central precocious puberty (CPP) during treatment with a gonadotropin-releasing hormone agonist (GnRHa) and compare these results with their healthy peers. METHODS: The Connor-Davidson Resilience Scale (CD-RISC) is a self-report scale used to quantify resilience, which is divided into seven subgroups (hardiness, coping, flexibility, purpose, optimism, regulation of emotion and cognition (REC), and self-efficacy). Fifty-one girls with CPP receiving GnRHa treatment and 51 healthy controls were involved in the study. Anthropometric measurements were evaluated and CD-RISC was performed at least six months after the initiation of GnRHa treatment. RESULTS: There was no statistically significant difference between the anthropometric evaluations of girls with CPP and the control group. Similarly, the total score and subgroup scores of patients with CPP and the control group showed no statistically significant difference. In the correlation analysis, there was a weak negative correlation between height and flexibility (r=-0.314 p=0.025), height SDS and flexibility (r=-0.254 p=0.092), height SDS, and purpose (r=-0.285 p=0.058). Also, there was a weak negative correlation between REC and weight (r=-0.435 p=0.003), REC and weight SDS (r=-0.461 p=0.002), REC and height (r=-0.269 p=0.077), REC and height SDS (r=-0.322 p=0.033), REC and BMI (r=-0.289 p=0.058), and REC and BMI SDS (r=-0.353 p=0.019). CONCLUSIONS: The resilience of girls with CPP treated with GnRHa was found to be similar to their healthy peers. The early diagnosis of the disease and adequate treatment may decrease the discrepancy of somatic changes between girls with CPP and their peers, which may help them to overcome the stress of CPP and long-term treatment.

Triglyceride-glucose index levels in patients with congenital hypogonadotropic hypogonadism and the relationship with endothelial dysfunction and insulin resistance.

INTRODUCTION: The risk of cardiometabolic diseases is increased in patients with hypogonadism. The triglyceride-glucose (TyG) index is a novel surrogate marker of insulin resistance and is associated with cardiovascular diseases. We investigated the TyG index levels and the relationship with endothelial dysfunction and insulin resistance in patients with congenital hypogonadotropic hypogonadism (CHH). MATERIAL AND METHODS: A total of 98 patients with CHH (mean age 21.66 ± 1.99 years) and 98 healthy control subjects (mean age 21.69 ± 1.21 years) were enrolled. The demographic parameters, TyG index, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. RESULTS: The patients had higher waist circumference (p < 0.001), triglycerides (p = 0.001), insulin (p = 0.003), HOMA-IR (p = 0.002), ADMA (p < 0.001), and TyG index (p < 0.001) levels and lower HDL-C (p = 0.044) and total testosterone (p < 0.001) levels compared to healthy control subjects. TyG index levels significantly correlated with the ADMA (r = 0.31, p = 0.003) and HOMA-IR (r = 0.32, p < 0.001) levels. TyG index was also determinant of HOMA-IR levels (ß = 0.20, p = 0.018). CONCLUSION: The results of the present study show that patients with CHH had increased TyG index levels. Also, the TyG index is independently associated with insulin resistance in patients with CHH. Long-term follow-up studies are warranted to find out the role of the TyG index in determining cardiometabolic risk in patients with hypogonadism.

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective: To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. Methods: The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. Results: The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged. Conclusion: The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Association of serum periostin levels with clinical features in children with asthma.

BACKGROUND: The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. METHODS: Children with physician-diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to the recent GINA guidelines. RESULTS: A total of 158 children (125 with asthma and 33 age- and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%), and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL, P < .001). The mean serum periostin levels in children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (P < .001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04-1.15, P < .001). When analyzed for the best cut-off value with the highest combined sensitivity and specificity, a cut-off value of 52 ng/mL for serum periostin level was obtained with sensitivity, specificity, PPV, and NPV of 100%, 50%, 29%, and 100%, respectively. CONCLUSION: Although serum periostin levels are higher in children with asthma, its diagnostic role in identifying children with severe asthma is limited.

Two Subsequent Metachroneus Solid Tumors: Oncocytic Variant Adrenocortical Carcinoma and Rhabdomyosarcoma of Childhood: Case Report and Literature Review

Most cases of malignancies appear to be sporadic, but some syndromes are associated with malignancies with germline variants. Herein, a child with an unusual association of oncocytic variant adrenocortical carcinoma (ACC) and rhabdomyosarcoma (RMS) was presented. An 18-month-old-boy was admitted with virilization of the genital area, penis enlargement and erection, which had begun six months earlier. Serum total testosterone (457 ng/dL; NR <10), androstenedione (3.35 ng/mL; NR <0.5) and dehydroepiandrosterone-SO4 (206 mcg/dL; NR<35) were above the normal ranges. Right adrenal mass was detected. After adrenalectomy, histopathological examination revealed an oncocytic variant ACC. Three-month after surgery, he then presented with 6x8 cm sized swelling of the left leg. Histopathological examination revealed embryonal RMS. Testing for tumor protein (TP53) variant by DNA sequence analysis was positive; however; fluorescence in situ hybridization analysis was negative. After chemotherapy and local radiotherapy, the patient is in good condition without tumor recurrence. Only about one-third of these tumors have a variant of TP53. This status also applies to other genetic variants related to cancer. However, a significant association of malignancies strongly suggests a problem in tumor suppressor genes or new variants. Another as yet unidentified suppressor gene may also be present and effective in this locus. The occurrence of ACC as a part of a syndrome and positive family history of malignancies in patients are clinically important. These patients and their families should be scanned for genetic abnormalities. The patient with ACC should be followed-up carefully for other tumors to detect malignancy early.

A Rare Cause of Hyperinsulinemic Hypoglycemia: Kabuki Syndrome

Kabuki syndrome (KS) is a disease characterized by distinctive facial features, skeletal anomalies and delay in neuromotor development. KS 1 is an autosomal dominant condition caused by mutations in the KMT2D gene, whereas KS 2 is an X-linked disorder caused by mutations in the KDM6A gene. In the majority of KS patients who present with hypoglycemia, KDM6A is the defective gene. A 9-month old girl was admitted to our emergency department due to a seizure. On physical examination, hypotonia, mild facial dysmorphism, brachydactyly of the 5th finger, prominent finger pads and pansystolic murmur were detected. A fasting glucose tolerance test was performed the next day due to her history of hypoglycemia, but she had convulsions at the fifth hour of the test. Her serum glucose was 24 mg/dL, insulin 1.94 mIU/L, C-peptide 0.94 ng/mL, growth hormone 11 ng/mL, anti-insulin antibody 4.2 IU/mL, cortisol 19.8 µg/dL, and adrenocorticotropic hormone 9.3 pg/mL. A diagnosis of hyperinsulinemic hypoglycemia was considered. Given the abnormalities, genetic analysis for congenital hyperinsulinism, including the genes causing KS was performed. A heterozygous frameshift mutation (c.2579del, p.Leu860Argfs*70) was detected in the KMT2D gene. Epilepsy and other neurological symptoms may be seen in KS patients and in some of these the neurological symptoms are the result of hypoglycemia. In such cases, the detection and prevention of hypoglycemia can help prevent the progression of neurological symptoms. We suggest considering the diagnosis of KS for patients with hypoglycemia and dysmorphic features, even if the patient does not manifest all features of KS.

Effect of adherence to carbohydrate counting on metabolic control in children and adolescents with type 1 diabetes mellitus.

PURPOSE: Carbohydrate counting provides better glycemic control and flexibility than other food planning methods. Consistent adherence to such a complex method is difficult, especially for youth. However, studies that determine adherence to this method and whether it alters metabolic control are limited. The aim of the current study was to determine adherence to this method and investigate its effect on metabolic control, anthropometric measurements, insulin dose, and energy intake. METHODS: In this prospective cross-sectional study, 53 children and adolescents with type 1 diabetes mellitus aged 2 to18 years and receiving intensive insulin therapy were trained and followed for 6 months. Demographics, anthropometrics, insulin requirements, hemoglobin A1c (HbA1c), fasting lipids, and food records at baseline and study conclusion were evaluated. At the end of the study patients were divided into adherer and nonadherer groups according to carbohydrate estimate deviations from standardized daily sample menus and calculations for accurate insulin doses. More than 10-g variation in daily consumed carbohydrate amount or failure to decide bolus insulin dose was defined as a nonadherer. RESULTS: The mean HbA1c, low-density lipoprotein cholesterol, and body mass index standard deviation score changed after the carbohydrate counting training while the mean HbA1c between groups was significant (P<0.05). Total daily insulin doses increased, and the mean high-density lipoprotein cholesterol levels decreased in both groups. There were significant correlations between HbA1c and carbohydrate deviation scores as well as HbA1c and caregiver's education level. CONCLUSION: Since adherence to carbohydrate counting may affect metabolic control, health professionals should evaluate and monitor carbohydrate counting skills of caregivers and patients in order to improve efficiency.

Nationwide Turkish Cohort Study of Hypophosphatemic Rickets

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.

Management of Thyrotoxicosis in Children and Adolescents: A Turkish Multi-center Experience

Objective: To determine the demographic and biochemical features of childhood and juvenile thyrotoxicosis and treatment outcome. Methods: We reviewed the records of children from 22 centers in Turkey who were diagnosed with thyrotoxicosis between 2007 to 2017. Results: A total of 503 children had been diagnosed with thyrotoxicosis at the centers during the study period. Of these, 375 (74.6%) had been diagnosed with Graves' disease (GD), 75 (14.9%) with hashitoxicosis and 53 (10.5%) with other less common causes of thyrotoxicosis. The most common presenting features in children with GD or hashitoxicosis were tachycardia and/or palpitations, weight loss and excessive sweating. The cumulative remission rate was 17.6% in 370 patients with GD who had received anti-thyroid drugs (ATDs) for initial treatment. The median (range) treatment period was 22.8 (0.3-127) months. No variables predictive of achieving remission were identified. Twenty-seven received second-line treatment because of poor disease control and/or adverse events associated with ATDs. Total thyroidectomy was performed in 17 patients with no recurrence of thyrotoxicosis and all became hypothyroid. Ten patients received radioiodine and six became hypothyroid, one remained hyperthyroid and restarted ATDs and one patient achieved remission. Two patients were lost to follow up. Conclusion: This study has demonstrated that using ATDs is the generally accepted first-line approach and there seems to be low remission rate with ATDs in pediatric GD patients in Turkey.