Anaemia-based screening for resistance to thyroid hormone alpha in children.

BACKGROUND: The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods. OBJECTIVE: The study aimed to assess the efficiency of a screening strategy for RTH-α. SUBJECTS AND METHODS: Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit. RESULTS: The median age of the patients was 5.7 (5.1-7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2-5.0) pg/mL, 0.9 (0.8-1.0) ng/dL, and 2.2 (1.8-3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH-α. CONCLUSIONS: This approach found one known patient with RTH-α but did not reveal any new cases. Notably, normo- or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH-α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Aromatase Inhibitors May Increase the Risk of Cardiometabolic Complications in Adolescent Boys.

INTRODUCTION: Aromatase inhibitors (AIs) are increasingly used in children and adolescents to augment adult height. The aim of this study was to investigate the effects AIs have on cardiac morphology, functions and their relation to several metabolic parameters in adolescent boys. METHODS: Three groups matched for sex (boys, n = 67), age (median age 13.5 years), weight, height, body mass index, and puberty stages were enrolled: (i) Group 1: 23 patients using AIs (only AI (n = 6) or in combination with growth hormone (GH) (n = 17)) for at least 6 months; (ii) Group 2: 22 patients using only GH, and (iii) Group 3: 22 healthy boys. Two-dimensional, M-mode conventional Doppler and tissue Doppler examinations of the left ventricle (LV) were performed. Bioelectrical bioimpedance analyses was conducted and follicle-stimulating hormone, luteinizing hormone, total testosterone, lipid, and hemogram parameters were obtained. RESULTS: Patients in Group 1 had significantly higher serum total testosterone (p < 0.001) and hemoglobin (p < 0.001) levels, fat free mass (p = 0.005), LV mass (LVM) (p = 0.002), as well as increased LV posterior wall diameter (LVPWD) (p = 0.002), interventricular septum diameter (IVSD) (p = 0.019), and myocardial systolic wave velocity (Sm) (p = 0.020) compared to the two other control groups. No significant differences were observed in terms of diastolic and systolic functions and lipid profiles (p > 0.05). There were positive correlations between total testosterone, hemoglobin levels, LVM, LVPWD and IVSD (p < 0.05). CONCLUSION: Increased LVM, LVPWD, IVSD and Sm of patients receiving AI therapy in comparison to the control groups, and the significant correlations of these parameters with total testosterone and hemoglobin levels were determined as potential side effects of AIs. These findings emphasize the need of routine cardiac follow-up in patients using AIs.

Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.

Metabolism has a role in determining the time of pubertal development and fertility. Nonetheless, molecular/cellular pathways linking metabolism/body weight to puberty/reproduction are unknown. The KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons in the arcuate nucleus of the hypothalamus constitute the GnRH (gonadotropin-releasing hormone) pulse generator. We previously created a mouse model with a whole-body targeted deletion of nescient helix-loop-helix 2 (Nhlh2; N2KO), a class II member of the basic helix-loop-helix family of transcription factors. As this mouse model features pubertal failure and late-onset obesity, we wanted to study whether NHLH2 represents a candidate molecule to link metabolism and puberty in the hypothalamus. Exome sequencing of a large Idiopathic Hypogonadotropic Hypogonadism cohort revealed obese patients with rare sequence variants in NHLH2, which were characterized by in-silico protein analysis, chromatin immunoprecipitation, and luciferase reporter assays. In vitro heterologous expression studies demonstrated that the variant p.R79C impairs Nhlh2 binding to the Mc4r promoter. Furthermore, p.R79C and other variants show impaired transactivation of the human KISS1 promoter. These are the first inactivating human variants that support NHLH2's critical role in human puberty and body weight control. Failure to carry out this function results in the absence of pubertal development and late-onset obesity in humans.

Clinical, genetic characteristics and treatment outcomes of children and adolescents with osteogenesis imperfecta: a two-center experience.

BACKGROUND: Osteogenesis imperfecta (OI), is a heritable, heterogeneous connective tissue disorder, characterized by fragile bones. There are conflicting results about genotype-phenotype correlations and efficiency of bisphosphonate treatment in this disorder. AIM: We aimed to evaluate the clinical, genetic characteristics, and long-term follow-up results of children and adolescents with OI. MATERIALS AND METHODS: A two-center retrospective study was conducted using demographic, clinical, and genetic data obtained from the medical records of the patients. RESULTS: Twenty-nine patients (62% male, median age; 3.6 years) with OI diagnosis from 26 families were included in the study. Thirteen different variants (nine were novel) were described in 16 patients in COL1A1, COL1A2, and P3H1 genes. Our siblings with homozygous P3H1 variants had a severe phenotype with intrauterine and neonatal fractures. Twenty-two patients were treated with bisphosphonates (17 of them with pamidronate, five with alendronate) with a median duration of 3.0 (1.6-4.8) years. Eleven patients (50%) suffered from fractures after the treatment. Haploinsufficiency variants in COL1A1 caused a milder skeletal phenotype with less fracture count and better treatment outcomes than structural variants. When compared with the anthropometric measurements at the initial diagnosis time, height Z-scores were lower on the last clinical follow-up (p = 0.009). CONCLUSIONS: We could not find an obvious genotype-phenotype correlation in Turkish OI patients with COL1A1 or COL1A2 variants. Treatment with pamidronate was effective in reducing fracture counts, without any long-term adverse effects.

The effect of leisure boredom and A1C level on diabetes eating problems in adolescents with type 1 diabetes.

PURPOSE: Eating out of boredom, the changes in daily routine, physical inactivity and longer exposure to screens have made glycemic control difficult at home during the COVID-19 pandemic among adolescents with Type 1 Diabetes Mellitus. Adolescents with diabetes are at higher risk of developing eating problems than are their healthy peers. The aim of this study is to examine the effects of leisure time boredom and A1C level on eating problems in adolescents with Type 1 Diabetes Mellitus. DESIGN AND METHODS: A descriptive, correlational, and cross-sectional design was used in this study. The study was conducted in Turkey, with the participation of 173 adolescents diagnosed with Type 1 Diabetes Mellitus. Convenience sampling was used to recruit patients from pediatric endocrinology outpatient clinics of hospitals. RESULTS: It was determined that the diabetes eating problems of adolescents with Type 1 Diabetes were mostly affected by the level of leisure time and A1C, respectively. In the overall model, 58% (F = 4119.701, p < .001) of the factors affecting diabetes eating problems could be explained by the level of leisure boredom and A1C level. CONCLUSION: It has been found that the adolescents with diabetes with high A1C levels and who cannot use their leisure time and have boredom are more at risk in terms of diabetes eating problems. PRACTICE IMPLICATIONS: It should be determined how the adolescents with diabetes spend their lesiure time by diabetes health care team, which should be supported to develop leisure time skills. Effective use of leisure time and strategies to cope with boredom should also be included in diabetes education.

Comparison of the Effectiveness of Adult Height Prediction Methods in Children with Growth Hormone Deficiency.

Background: In patients with growth hormone (GH) deficiency, the prediction of adult height before initiation of GH treatment can be helpful to guide clinicians and families. However, data regarding the effectiveness of prediction methods in such patients are limited.Objective: We aimed to investigate the accuracy of the three most used adult height prediction methods [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their results with the near-adult height (NAH) data of children treated with GH.Methods: A single-center retrospective study was conducted including patients treated with somatotropin due to GH deficiency. Bone age radiographs were reread by three authors. Adult height predictions were made using BP, RWT, and TW2 methods for each patient.Results: Forty-nine patients with GH deficiency [median age at diagnosis 10.8 (9.2-12.0) years, 63.3% girls, 69.4% prepubertal] were included. Median differences between predicted adult height (PAH) and NAH standard deviation (SD) scores were -0.5, 0.0, and 0.3 for BP, RWT, and TW2 methods, respectively. The rates of PAH within ±1 SD score of NAH were 54.7%, 62.3%, and 77.4% for BP, TW2, and RWT methods, respectively. RWT was the most accurate method in girls, however, it showed a similar efficiency with TW2 in prepubertal patients or those with delayed bone age between 1-2 years, independent of gender.Conclusions: We found that RWT and TW2 methods may be preferable rather than the BP method for predicting adult height in patients with a diagnosis of GH deficiency.

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aim: We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH). Materials and methods: Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) "uncontrolled" [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) "controlled" [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system. Results: There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status. Conclusion: In this study, the CIMT values of CAH cases were similar to those of healthy subjects.

Comparison of the effectiveness of simple carbohydrates on hypoglycemic episodes in children and adolescents with type 1 diabetes mellitus: A randomized study in a diabetes camp.

BACKGROUND: Hypoglycemia is the most common and severe complication of insulin treatment during the management of type 1 diabetes mellitus (T1DM). Despite its importance, there is a lack of data about the efficacy and superiority of the carbohydrate sources used in hypoglycemia management in children and adolescents. OBJECTIVE: We aimed to compare the effectiveness of honey, fruit juice, and sugar cubes as simple carbohydrates used in the primary treatment of hypoglycemia in children and adolescents with T1DM, who attended a diabetes summer camp. METHODS: A prospective randomized study was performed in a 5-days-long diabetes summer camp. Three different types of simple carbohydrates; sugar cubes, honey, or fruit juice were randomly given for the treatment of hypoglycemia and the recovery results in the three groups were compared. RESULTS: About 32 patients (53.1% male, mean age 12.9 ± 1.9 years) were included and 158 mild hypoglycemic episodes were observed. Sugar cubes, honey, and fruit juice were given in 46 (29.1%), 60 (37.9%), and 52 (33%) events, respectively. We found that honey and fruit juice had similar efficiency in recovering hypoglycemia in 15 minutes with a rate of 95% and 98%, respectively. However, sugar cubes had a significantly lower impact on treatment of hypoglycemia than the others, with a recovery rate of 84.7% at 15 minutes. CONCLUSIONS: This study showed, for the first time, that honey and fruit juice were more effective in treating hypoglycemia than sugar cubes, and can be preferred in treating hypoglycemic events in children and adolescents with T1DM.

Impaired systolic and diastolic left ventricular function in children and adolescents with congenital adrenal hyperplasia receiving corticosteroid therapy.

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia. METHODS: The study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (>10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging. RESULTS: Patients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p<0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p<0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p<0.05). CONCLUSION: This study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

Effects of a home-based nursing intervention programme among adolescents with type 1 diabetes.

AIMS AND OBJECTIVE: To investigate the effects of a home-based nursing intervention programme established based on the Health Promotion Model on the health outcomes of adolescents with type 1 diabetes mellitus. BACKGROUND: After diagnosed with diabetes, it is necessary to ensure that nursing care is not limited to the hospital setting but continues at home. DESIGN: A quasi-experimental design with a pre- and post-test control group was used. The researchers have complied with the guidelines of TREND Checklist in presenting this study. METHOD: This study was conducted in Izmir, Turkey, with 71 adolescents (35 in an intervention group and 36 in a control group) diagnosed with type 1 diabetes mellitus who were registered at the paediatric endocrinology outpatient clinics of two hospitals and were selected using the convenience sampling method between June-December 2017. A home-based nursing intervention programme (5 week) was provided to the intervention group while standard care was provided to the control group. Data were collected at the baseline, and 3 and 6 months after a 5-week home-based nursing intervention. Multi-way and one-way analysis of variance, the Bonferroni correction, regression analysis, t test, chi-squared analysis and a structural equation model were used for data analysis of the iterative measurements. RESULTS: At the end of the home-based nursing intervention programme, the HbA1c mean scores significantly decreased, while self-efficacy perception, frequency of managing diabetes and taking responsibility in managing diabetes increased in the intervention group compared to those in the control group. Frequency of admission to the hospital and average costs were lower in the intervention group than in control group. The home-based nursing intervention programme using structural equation modelling increased the frequency of managing diabetes and taking responsibility in managing diabetes and decreased HbA1c levels. CONCLUSION: The home-based nursing intervention programme was effective in decreasing HbA1c levels, increasing the frequency of diabetes management and taking responsibility in managing diabetes, and improving the self-efficacy of the adolescents. RELEVANCE TO CLINICAL PRACTICE: The home-based nursing intervention programme can be applied by nurses to ease the transition of adolescents with type 1 diabetes mellitus and their parents to healthy daily life practices and ensure their glycemic controls after being discharged.

Can ambulatory blood pressure monitoring detect early diastolic dysfunction in children with type 1 diabetes mellitus: correlations with B-type natriuretic peptide and tissue Doppler findings.

AIM: To evaluate the relationship between 24-h blood pressure (BP) measurements and diastolic heart function evaluated by Doppler tissue imaging and B-type natriuretic peptide (BNP) levels in children with type 1 diabetes mellitus (DM). PATIENTS AND METHODS: A total of 32 diabetic and 18 healthy children were enrolled. Spectral Doppler analysis and tissue Doppler measurements were performed by conventional echocardiography. The 24-h ambulatory BP and serum BNP levels were measured. RESULTS: Analysis of ambulatory blood pressure monitoring (ABPM) recordings showed that median daytime diastolic BP load were significantly higher in diabetic patients compared to controls [12.35 (4.23-27.23) vs. 2.5 (0-8.7), p = 0.007]. Patients with elevated daytime systolic and diastolic BP loads had significantly higher BNP values compared to patients with normal BP load (31.4 ± 24.36 vs. 11.84 ± 11.25 pg/mL, p = 0.03 and 23.21 ± 15.12 vs. 12.12 ± 14.65 pg/mL, p = 0.03, respectively). Isovolemic contraction time (47.43 ± 7.84 vs. 42.27 ± 7.47, p = 0.045), isovolemic relaxation time (68.84 ± 10.43 vs. 58.77 ± 10.02, p = 0.02), and myocardial performance index (0.45 ± 0.10 vs. 0.37 ± 0.09, p = 0.02) as determined by tissue Doppler echocardiography were significantly high in diabetic patients compared to that of control cases. Ratio of mitral peak early diastolic flow velocity (E) to peak early diastolic myocardial velocities by tissue Doppler echocardiography (E') was also higher in patients with elevated daytime systolic BP load (E/E', 6.71 ± 1.97 vs. 4.91 ± 1.02, p = 0.04). CONCLUSION: Elevated BP loads detected by 24-h ambulatory BP measurements in children with type 1 diabetes are associated with increased BNP levels and abnormal tissue Doppler echocardiography indices, indicating early stage cardiac dysfunction.

Isolated hyperthyrotropinemia in childhood obesity and its relation with metabolic parameters.

PURPOSE: The aim of the presented study was to evaluate the prevalence of isolated hyperthyrotropinemia (IH) in obese children and the relation between anthropometric and metabolic parameters. METHODS: Hospital records of the children, who presented to the Pediatric Endocrinology outpatient clinic of our institution with obesity, and age and gender-matched healthy children, who had undergone thyroid function test for any reason were retrospectively reviewed. RESULTS: The prevalence of IH was significantly higher in the obese group than in the controls (9.2 and 3.8 %, respectively). Body mass index-standard deviation score (BMI-SDS), thyroid-stimulating hormone (TSH), lipid parameters were significantly different in the obese group than in the control group. A positive correlation between TSH and BMI-SDS and negative correlation between TSH and free T4 (fT4) levels were found in obese subjects. Stepwise multiple linear regression analysis confirmed that BMI-SDS, fT4 and triglyceride levels were the strongest independent variables correlated with TSH level in obese subjects (r (2) = 0.046, p = 0.001). CONCLUSIONS: IH prevalence is higher in obese children as compared to healthy children and the increase in TSH level correlates negatively with serum fT4 and positively with BMI-SDS and triglyceride levels in obese children.

Salivary Sex Steroid Levels in Infants and the Relation with Infantile Colic

Objective: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic.

Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community.

OBJECTIVE: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH). CONTEXT: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease. DESIGN: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families. PATIENTS: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families. MEASUREMENTS: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out. RESULTS: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N). CONCLUSIONS: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.

The relation of serum nesfatin-1 level with metabolic and clinical parameters in obese and healthy children.

BACKGROUND: Nesfatin-1, a recently discovered anorexigenic neuropeptide, is expressed in several tissues including pancreatic islet cells and central nervous system. This peptide seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis. OBJECTIVE: We aimed to investigate the relation of serum nesfatin-1 level with metabolic and anthropometric parameters in obese children. METHODS: The study included obese children with a body mass index (BMI) above the 95th percentile and healthy children with a BMI below the 85th percentile. The healthy and obese subjects had similar age and gender distribution. Fasting serum glucose, insulin, lipid profile, and nesfatin-1 levels were measured to evaluate metabolic parameters. RESULTS: Obese group (n = 37) had significantly higher BMI, BMI-SDS (standard deviation score of BMI), triglyceride, insulin, and insulin resistance index by the homeostasis model assessment, systolic and diastolic blood pressure values compared with the control group (n = 31) (p < 0.05). Serum nesfatin-1 level of the obese subjects was significantly lower than that of the control subjects (p = 0.001). No statistically significant difference was found when nesfatin-1 levels were compared among obese patients regarding the presence of insulin resistance (p = 0.202). In the obese group, nesfatin-1 level was negatively correlated with BMI-SDS, but not with insulin resistance index (p = 0.02 and p = 0.361, respectively). CONCLUSIONS: This is the first study to evaluate nesfatin-1 levels in relation with anthropometric and metabolic parameters in obese patients who had significantly lower nesfatin-1 levels. Our results underline that nesfatin-1 may play an important role in regulation of food intake in obese individuals.

Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation.

3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score -5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score -5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8-10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.

Clinical and diagnostic characteristics of hyperprolactinemia in childhood and adolescence.

Pituitary adenoma is the most common cause of hyperprolactinemia, which is a rare endocrine disorder encountered in pediatric patient care. Epidemiological and clinical information about hyperprolactinemia in childhood and adolescence is limited. Clinical signs of hyperprolactinemia are very heterogeneous. In girls, disturbances in menstrual function and galactorrhea may be seen, whereas in boys, headache, visual disturbances, delayed pubertal development and hypogonadism are often present. Owing to the ease of ordering a serum prolactin measurement, an evidence-based, cost-effective approach to the management of this endocrine disorder is required. Before a diagnosis of hyperprolactinemia is made, drug use, renal insufficiency, hypothyroidism, and parasellar tumors should be excluded. The main objectives of treatment are normalization of prolactin level, adenoma shrinkage, and recovery from clinical signs related to hyperprolactinemia. In patients with microadenoma, invasive or non-invasive macroadenoma, and even in patients with visual field defects, dopamine agonists are the first-line treatment. Surgical treatment is indicated in patients who are unresponsive or intolerant to medical treatment or who have persistent neurological signs. Radiotherapy should be considered as a supportive treatment for patients in whom surgery fails or medical response is not achieved.

A novel mutation in a mother and a son with Aarskog-Scott syndrome.

Aarskog-Scott syndrome, also termed as faciogenital dysplasia, is an X-linked disorder consisting of short stature, craniofacial dysmorphism, shawl scrotum, cryptorchidism, and interdigital webbing. Cardiac and central nervous system abnormalities and behavioral disorders can also be detected. The gene responsible for the syndrome is called FGD1, located at Xp11.21. A 7-year-old boy was admitted to our hospital due to short stature. He was born to non-consanguineous parents after an uneventful term pregnancy. Orchiopexy for bilateral cryptorchidism was performed when he was 2 years old. At physical examination, his height was under 3 percentile, and he had broad nasal bridge, hypertelorism, wide philtrum, brachydactyly, and interdigital webbing. Cranial magnetic resonance imaging and echocardiography revealed normal findings. An eye examination showed amblyopia and astigmatism. The mother had short stature and interdigital webbing as well. Mutational analyses revealed a novel mutation (c.308-2G), hemizygous in the boy and heterozygous in the mother. Aarskog syndrome (faciogenital dysplasia) should be kept in mind in children with short stature and interdigital webbing.

Endocrinological and cardiological late effects among survivors of childhood acute lymphoblastic leukemia.

OBJECTIVE: Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. MATERIALS AND METHODS: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. RESULTS: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. CONCLUSION: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases. CONFLICT OF INTEREST: None declared.