Sleep disturbances in children and adolescents with type 1 diabetes mellitus: Prevalence, and relationship with diabetes management.

OBJECTIVE: A decline in sleep quality and regularity has been reported in patients with type 1 diabetes mellitus (T1D) in many studies. However, research on medical-based sleep disorders in patients with T1D is limited. Diagnosing sleep disorders is crucial, as it negatively impacts academic performance, cardiovascular health, and cognitive functions among children as well as essential skills for effective diabetes management. Our objective was to assess sleep disturbances in patients diagnosed with T1D and explore whether these patients experience significantly more sleep disturbances compared to their healthy peers. METHODS: This study, designed as a cross-sectional case-control investigation, involved a cohort of 250 participants (144 T1D, 106 control cases) aged 6-15 years. The Sleep Disturbance Scale for Children (SDCS) scores of the T1D group were compared with those of the control group. Furthermore, the study explored the correlation between clinical/biochemical parameters and SDCS scores within the T1D group. RESULTS: The mean age of individuals in the T1D group was 10.27 ± 3.25 years, while the control group had a comparable mean age of 10.48 ± 3.5 years (P = 0.303). Within the T1D group, the median duration of diabetes was 5 (1-15) years, and the median glycosylated hemoglobin A1c (HbA1c) level for the past one year was 8.4 %. Although there was no significant difference in total SDSC scores between the T1D and control groups, both groups exhibited average scores that remained close to the threshold indicative of sleep disturbances (>39). Notably, individuals with total SDSC scores surpassing 39 were identified at rates of 48.6 % in the T1D group and 47.6 % in the control group, respectively. Furthermore, disorders of arousal nightmares (DA) were more prevalent in T1D patients compared to their healthy peers (P = 0.049). Additionally, HbA1c showed a positive correlation with scores for disorders of excessive somnolence (DOES) and total scores (P < 0.001, R = 0.368; P = 0.003, R = 0.243). CONCLUSION: Our study found that the prevalence of sleep disturbances among children and adolescents with T1D was not significantly higher than that observed in their healthy peers. Nevertheless, it is crucial to note that a notable portion, 48.6 % of T1D cases and 47.6 % of healthy cases, displayed sleep disturbances based on SDSC scores. To optimize diabetes management and proactively address potential challenges, incorporating routine screening for sleep disturbances in the monitoring of T1D patients can yield valuable benefits.

Evaluation of the growth response of children with growth hormone deficiency according to the peak growth hormone levels in provocation tests.

BACKGROUND: We aimed to evaluate the relation between the peak growth hormone (GH) levels in provocation tests and response to recombinant human GH (rhGH) therapy in patients with GH deficiency (GHD). METHODS: This was a cross-sectional, single-center, and retrospective study. A total of 135 patients under the age of 16 years who were diagnosed with GHD through insulin tolerance tests and L-DOPA stimulation tests and who received rhGH therapy for at least 2 years in the Pediatric Endocrinology Clinic of Akdeniz University Hospital between 1997 and 2021 were included in the study. RESULTS: The patients were divided into two groups: idiopathic GHD (group I, n = 119) and multiple pituitary hormone deficiencies or organic pathology on magnetic resonance imaging (group II, n = 16). The patients in group I were classified into three subgroups according to the peak GH values in the provocation tests (group Ia: peak GH <3 µg/L, n = 34; group Ib: peak GH between 3 and 7 µg/L, n = 71; group Ic: peak GH between 7 and 10 µg/L, n = 34). The median age was 11.5 years in group I (8.8 in group Ia, 12.1 in group Ib, 12.3 in group Ib) and 8.8 years in group II. The height standard deviation score (SDS) was -2.93 in group I (-2.85 in group Ia, -2.99 in group Ib, -2.94 in group Ic) and -3.79 in group II. The median Δheight SDS was 0.61 in group I and 1.05 in group II at the end of the first year of treatment and 0.31 in group I and 0.45 in group II at the end of the second year (p = 0.005 and p = 0.074, respectively). When the subgroups of group I were compared, height SDS, Δheight SDS, and height velocity (HV) SDS were all higher in group Ia at the end of the first year of rhGH therapy (p = 0.040, p = 0.029, and p = 0.005, respectively). The height SDS was still significantly higher in group Ia (p = 0.033) while the HV SDS and Δheight SDS were similar between the groups at the end of the second year of therapy (p = 0.164 and p = 0.522, respectively). There was a statistically significant association between the first-year HV SDS and the peak GH value in provocation tests in multiple regression analyses (p<0.001). In addition, the final model revealed that height SDS and weight SDS at the start of the treatment and the first-year HV SDS are the factors with a statistically significant effect on the second-year HV SDS (p = 0.022, p = 0.001, and p<0.001, respectively). CONCLUSION: Our findings show that the lower the GH peak in provocation tests, the better the response to treatment. The best HV was observed in the first year of rhGH therapy, and the diagnosis should be checked in those patients who had a low first-year HV and did not have a severely low GH peak in provocation tests.

Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.

Elevated Selenoprotein P Levels in Thalassemia Major Patients.

INTRODUCTION: Previous studies have measured selenium levels and glutathione peroxidase 3 (GPX3) activity in patients with thalassemia major (TM). However, Selenoprotein P (SEPP), which is responsible for the storage and transport of selenium, has not been studied in thalassemia patients. This study aims to correlate thyroid functions of TM patients with their SEPP and GPX3 levels. MATERIALS AND METHODS: Eighty subjects (40 controls, 40 TM patients) were included in this study. GPX3 and SEPP concentrations were measured in all subjects using sandwich ELISA. Iron, ferritin, urinary iodine, thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), anti-thyroid peroxidase (anti-TPO), and anti-human thyroglobulin (anti-hTG) concentrations were also measured. RESULTS: Mean SEPP concentration was higher in the TM group compared to the control group. A slight elevation in GPX3 levels was also observed in thalassemia patients, yet it was not statistically significant. In both TM patients and controls, ferritin was inversely correlated with free T4 concentration and GPX3 was inversely correlated with free T4 and T3 concentrations. There was also a negative correlation between SEPP and TSH concentrations in healthy subjects. CONCLUSION: This is the first study, which has measured SEPP concentrations in thalassemia patients. SEPP levels were higher in TM patients compared to controls. Correlations between thyroid hormones and selenoproteins may indicate that selenium is necessary for thyroid function. Detailed studies are required to elaborate the role of SEPP in thyroid metabolism in thalassemia patients.

Psychiatric Disorders and Peer-Victimization in Children and Adolescents With Growth Hormone Deficiency.

In this study, we aimed to investigate psychiatric disorders, bullying/victimization, and quality of life in children and adolescents with idiopathic growth hormone deficiency (GHD). Sixty-one children and adolescents who were diagnosed as having idiopathic GHD were evaluated using a semistructured interview by a child and adolescent psychiatrist. Some 45.9% of the subjects with GHD were diagnosed with at least 1 psychiatric disorder. The most common psychiatric diagnosis was social anxiety disorder (18.3%). Twenty-eight percent of the subjects reported being bullied by their peers. Victimization rates were less frequent in those treated for more than 1 year. Children aged between 6 and 12 years had poorer quality of life and higher anxiety levels than adolescents aged between 13 and 18 years. Due to the higher rates of existing psychiatric disorders, the clinical management of patients with GHD should be conducted with a multidisciplinary approach, in which pediatric endocrinologists and mental health professionals work in coordination.

Hyperandrogenism correlates with psychological symptoms in adolescents with polycystic ovary syndrome.

This study aimed to analyze the depressive and anxiety states of adolescent girls with polycystic ovary syndrome (PCOS). This was a cross-sectional, multicenter, case-control study. A total of 100 participants (PCOS group, 51; control group, 49) aged 13-18 yr were included in the study. Body mass index was higher in patients with PCOS (P = 0.002). In the PCOS group, 28.5% of the patients had moderate-to-severe depressive symptoms, whereas the incidence was lower in controls (8.3%, P = 0.021). The State-Trait Anxiety Inventory (STAI)-State, STAI-Trait, and physical, psychosocial, and total Pediatric Quality of Life Inventory PedsQL scores were higher in the PCOS group, suggesting that anxiety was more common and the quality of life was worse in patients with PCOS than in healthy participants (P = 0.01, P = 0.03, P = 0.02, P = 0.046, and P = 0.047, respectively). The serum free testosterone (fT) levels were positively correlated with the depression and anxiety scores and negatively correlated with the psychosocial PedsQL scores. In conclusion, adolescent girls diagnosed with PCOS demonstrated higher depressive and anxiety symptoms and lower psychosocial quality of life scores than their healthy counterparts. A relationship was found between the fT level and all psychological measures.

The Examination of the Relationship Between COVID-19 and New-Onset Type 1 Diabetes Mellitus in Children.

OBJECTIVE: This study aimed to evaluate presentations of new-onset type 1 diabetes mellitus in a pediatric cohort during the coronavirus disease 2019 pandemic. MATERIALS AND METHODS: This study was designed as a single-center, descriptive, cross-sectional retrospective study. The patients diagnosed with new-onset type 1 diabetes mellitus between April 1, 2020, and April 1, 2021, were included in the study. The rate of severe acute respiratory syndrome coronavirus 2 polymerase chain reactivity-positivity was investigated. The pandemic period was compared with the same period of the pre-pandemic 2 years in terms of number of new-onset type 1 diabetes mellitus patients, rate of presentation with diabetic ketoacidosis, and degree of diabetic ketoacidosis severity. RESULTS: In total, 56 patients were diagnosed with type 1 diabetes mellitus during the pandemic and 2 (3.57%) of them tested positive for severe acute respiratory syndrome coronavirus 2 polymerase chain reaction. The number of new-onset type 1 diabetes mellitus patients was 39 in 2019 and 39 in 2018. The rate of presentation with diabetic ketoacidosis was similar in the pandemic period compared to the pre-pandemic periods (53.5% in 2020 vs. 56.4% in 2019 and 53.8% in 2018; P = .94). The proportion of severe diabetic ketoacidosis was also similar in all years, respectively (43.3% in 2020 vs. 45.4% in 2019 and 47.6% in 2018; P = .95). CONCLUSION: We reported only 2 cases that tested positive for severe acute respiratory syndrome coronavirus 2among the new-onset type 1 diabetes mellitus patients during the pandemic. Although we found an increase in the number of new-onset type 1 diabetes mellitus cases by comparing with prepandemic period, rates of diabetic ketoacidosis and severe diabetic ketoacidosis were similar. There was no finding to suggest that severe acute respiratory syndrome coronavirus 2taking a part in type 1 diabetes mellitus pathogenesis. Since the development of type 1 diabetes mellitus is a long process, prospective studies are needed to investigate the long-term effects of severe acute respiratory syndrome coronavirus 2.

Effects of methylphenidate on height, weight and blood biochemistry parameters in prepubertal boys with attention deficit hyperactivity disorder: an open label prospective study.

Background: Adverse effects of stimulants on growth in children have long been studied, but the results remain to be clarified, because metabolic changes or predictors accompanying the growth deviations were not sufficiently studied. Objective: This open label-prospective study investigated the effects of methylphenidate (MPH) on weight, height, blood biochemistry in children with attention deficit hyperactivity disorder (ADHD). Method: Prepubertal boys treated with MPH in Child and Adolescent Psychiatry Clinic at Antalya Training and Research Hospital in Health Sciences University, Turkey were recruited. Height and weight z-scores and fasting blood samples were taken at baseline and 6th month. Changes were compared by paired-samples t-test or Wilcoxon signed-rank test. Any association between the changes in growth and biochemical values was analyzed by Spearman's Rank-Order Correlation. The statistical significance threshold was p<0.01. Results: 31 boys aged 74 to 104 months were enrolled in the study sample (mean=87.6, Standard Deviation (SD)=9.2). Osmotic release oral system-MPH (18 mg/day) was used in 77.4% (N=24) and immediate release-MPH (5 mg three times a day) in 22.5% (N=7). Average daily drug dose was 0.66 mg/kg (SD=0.12). Baseline weight z-score was 0.63 (SD=1.12), decreased significantly at 6 months (0.24 [SD=1.04]) (Z=-4.44, p=0.000, r=0.5) (median z-score was 0.53 at baseline, -0.11 at 6 months). Baseline height z-score (0.23[SD=0.87]) was not suppressed significantly at 6 months (0.28[SD=0.85])(t(30) = ‒1.50, p=0.14). Glucose (t(30) = -4.33, p=0.000, r=0.6), creatinine (t(30)=-3.28, p=0.003, r=0.5) and 25OH-VitD (N=29, Z=-3.98, p=0.000, r=0.5) increased but alkaline phosphatase (ALP) decreased (t(28)=3.63, p=0.001, r=0.5). The differences in W-SDS and ALP were positively correlated (r=0.47, p=0.009). Conclusions: Our results indicate the importance of monitoring blood variables that may accompany growth changes early in MPH treatment and should be further assessed in larger samples.

Psychiatric disorders, peer-victimization, and quality of life in girls with central precocious puberty.

OBJECTIVE: To evaluate the psychiatric diagnoses, peer-victimization, quality of life, and emotional and behavioral status of girls with central precocious puberty (CPP). METHODS: A total of 71 girls with CPP and 50 healthy controls participated in the study. All participants were evaluated using a semi-structured interview by a child and adolescent psychiatrist. To assess the peer-victimization, quality of life, depression levels, and emotional and behavioral status, the Olweus Bully/Victim Questionnaire, The Pediatric Quality of Life Inventory (PedsQL), the Child Depression Inventory (CDI) and Strengths and Difficulties Questionnaire (SDQ) was used in this study. RESULTS: Although the difference was not significant, the rate of being diagnosed with at least one psychiatric disorder was higher in CPP group (28%) than in control group (20%). The most common psychiatric disorder was social anxiety disorder (13%) for the CPP group. No significant difference was found between the CPP and the control groups in terms of mean CDI and PedsQL scores. When compared in terms of SDQ parameters, prosocial behavior scale scores were significantly higher in the CPP group than in the control group. Being a victim of bullying was found significantly more frequently in girls with CPP than among the healthy controls (28% vs. 12%). CONCLUSION: Due to the high rates of being bullied, girls with CPP should be screened for peer-victimization. Long-term prospective studies are also necessary to further elucidate the psychological consequences of CPP on girls.

Increased potassium excretion in children with monosymptomatic nocturnal enuresis: could it be related to Kir 4.1- KCNJ10 gene polymorphism?

BACKGROUND AND OBJECTIVES: There are controversial results in the literature regarding urinary electrolytes, especially potassium, in enuretic children. KCNJ10 channel protein, a member of the Kir 4.1 family is expressed in renal distal tubules and has an important function in renal ion transport. We investigated whether KCNJ10 gene polymorphisms are associated with clinical and laboratory findings of a group of Turkish children with monosymptomatic primary nocturnal enuresis (MNE). METHOD: Ninety-seven MNE children and 100 healthy controls were tested for three single nucleotide polymorphisms (SNPs) in the KCNJ10 gene. The transversions in SNPs were G to A for intron 1(SNP1), G to A for exon 2 (SNP2), and T to C transition for promoter (SNP3). All SNPs were genotyped by PCR-restriction fragment length polymorphism. RESULTS: SNP3 in promoter of KCNJ10 gene showed strong association with MNE children for distribution of genotype and allele frequency, while SNP1 in intron 1 and SNP2 in exon 2 were noninformative. The distribution of TT, TC, and CC genotypes for SNP3 was 66%, 26.8% and 7.2% respectively in MNE compared with 38%, 59% and 3% respectively in controls (p < 0.0001). In enuretic children, TT genotype was higher and there was an increased potassium excretion in children with TT genotype (P < 0.05). CONCLUSION: We conclude that KCNJ10 gene promoter polymorphism may have a role on potassium excretion in Turkish MNE children. This is the first study in literature evaluating KCNJ10 gene polymorphism in this patient population. Future studies investigating the other SNPs, mutations or altered regulation of Kir4.1 in larger samples would help clarify the role (s) of KCNJ10 gene in enuresis.

The molecular basis and genotype-phenotype correlations of congenital adrenal hyperplasia (CAH) in Anatolian population.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population.

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.

In vitro evaluation of nebivolol effects on nonadrenergic noncholinergic responses in rabbit corpus cavernosum.

The purpose of this study was to compare the effects of nebivolol on nonadrenergic noncholinergic (NANC) relaxation functions that are mediated by electric field stimulation (EFS) in rabbit corpus cavernosum smooth muscle by comparison with other beta-adrenergic receptor blockers and show the level on which its effects through nitric oxide take place. After the effects of nebivolol on the isolated corpus cavernosum tissues that were contracted through the alpha-adrenergic pathway and application of L-NAME' (NG -nitro-L-arginine methyl ester) which is a competitive inhibitor of nitric oxide synthase (NOS), the changes that occurred were recorded. Following the effect on the tissue that was contracted with phenylephrine in the presence of atropine and guanethidine that was created by EFS, nebivolol and other beta-blockers were added and the changes were recorded. After receiving relaxation responses with EFS-mediated NANC, no difference was observed between the relaxation responses due to addition of nebivolol and other beta-adrenergic blockers (p > 0.05). The finding that nebivolol which has a NO-mediated relaxation effect did not have an effect on EFS-mediated NANC relaxation but created relaxation on the tissue that was contracted by phenylephrine and the effect was reversed by L-NAME, shows that its effects are on a postsynaptic level.

Restless legs syndrome in children with allergic rhinitis: A comparative study on frequency, severity and sleep quality.

OBJECTIVES: This study aims to investigate the frequency and severity of restless legs syndrome (RLS) and its relationship with sleep quality in children with allergic rhinitis (AR) with the hypothesis that comorbid RLS may be an additional causative factor of sleep disturbances in pediatric AR. PATIENTS AND METHODS: A total of 143 children with AR (aged 8-18 years) and 144 healthy control subjects (aged 8-18 years) were included. The diagnosis of AR was established on history, clinical examination and skin prick test according to the Allergic Rhinitis and its Impact on Asthma guidelines. Presence of RLS was determined using the International RLS study group (IRLSSG) criteria. The severity of RLS was assessed using the IRLSSG rating scale. Sleep quality was evaluated by Pittsburgh Sleep Quality Index (PSQI). RESULTS: Thirteen patients (9.1%) in AR group, and six children (4.2%) in control group had RLS (p=0.159). The frequency of RLS in AR group was higher than two folds when compared to the control group; however, the difference was not statistically significant. Restless legs syndrome severity score was significantly higher in AR group than control group (15.00 [11-20] and 11.00 [10-16] respectively, p=0.046). Total PSQI scores were similar between groups. Also, no significant differences were observed in total PSQI scores of AR patients with or without RLS. CONCLUSION: Restless legs syndrome was not more common but was more severe in children with AR. There was no evidence that RLS has an obvious effect on sleep quality in children with AR.

Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome.

Autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) is a rare but devastating primary immunodeficiency disease caused by loss-of-function mutations in autoimmune regulator (AIRE) gene on chromosome 21q22.3. The clinical spectrum of the disease is characterized by a wide heterogeneity because of autoimmune reactions toward different endocrine and non-endocrine organs. Here, we report a 17-year-old Turkish girl diagnosed with APECED at 9 years in whom a novel homozygote mutation in AIRE gene p.R15H (c.44G>A) was found. In the clinical course of the patient, chronic liver disease due to autoimmune hepatitis has evolved resulting in hepatopulmonary syndrome (HPS) which has not been reported before in patients with APECED.

Basal Serum Neurokinin B Levels in Differentiating Idiopathic Central Precocious Puberty from Premature Thelarche.

OBJECTIVE: To find out the diagnostic role of kisspeptin and neurokinin B in idiopathic central precocious puberty (ICPP) and premature thelarche (PT). METHODS: The girls who presented with early breast development before the age of 8 years were evaluated. Patients with intracranial pathologies were excluded. Basal and stimulated follicle-stimulating hormone/luteinizing hormone (LH) levels and basal neurokinin B/kisspeptin levels were measured. Patients who had peak value of LH >5 mIU/mL and a bone age (BA)/chronological age (CA) ratio >1.1 were diagnosed as central precocious puberty (CPP), while cases who did not meet these criteria were diagnosed as PT. Healthy age-matched prepubertal girls were included as the control group. RESULTS: The study group contained 25 girls with ICPP (7±0.8 years), 35 girls with PT (6.8±0.7 years), and 30 controls (6.7±0.7 years). Basal serum kisspeptin and neurokinin B levels were 2.36±0.47 ng/mL and 2.61±0.32 ng/mL, respectively in the ICPP group, 2.23±0.43 ng/mL and 2.24±0.23 ng/mL, respectively in the PT group, and 1.92±0.33 ng/mL and 2.03±0.24 ng/mL, respectively in the controls. Both kisspeptin and neurokinin B levels were higher in the ICPP and PT groups compared to controls (p<0.05). Moreover, basal neurokinin B level was different between ICPP and PT groups (p<0.01). A serum neurokinin B level of 2.42 ng/mL provided the most appropriate level to differentiate ICPP from PT, with a sensitivity of 84% and specificity of 77.1%. CONCLUSION: Differentiation of CPP from PT is sometime difficult, and there is a need for a simple method for the differential diagnosis. Our results suggest that basal serum neurokinin B level can be used as an adjunctive parameter to differentiate ICCP from PT.

Comparative Relaxant Effects of Ataciguat and Zaprinast on Sheep Sphincter of Oddi.

BACKGROUND: Relaxing the sphincter of Oddi (SO) is an important process during endoscopic retrograde cholangiopancreatography (ERCP) procedures. This issue suggests that the easier the sphincterotomy and cannulation, the more post-ERCP complications decrease. AIMS: To compare the relaxant effects of ataciguat (a novel soluble guanylyl cyclase activator) and zaprinast (an inhibitor of phosphodiesterase 5) on sheep SO in vitro, thus testing whether they can be used during ERCP. STUDY DESIGN: Animal experimentation. METHODS: Sheep SO rings were placed in tissue baths and their isometric tension to ataciguat and zaprinast were tested. We also tested their isometric tension against ataciguat in the presence of 1H-(1,2,4) oxadiazole (4,3-a) quinoxalin-1-one (ODQ) which is a soluble guanylyl cyclase inhibitor. RESULTS: Ataciguat and zaprinast both triggered concentration addicted relaxation on sheep SO rings (p=0.0018, p=0.0025 respectively) but the relaxation of the ataciguat was significantly greater than that of zaprinast at all concentrations (p=0.0024). It was observed that decreased relaxation responses were initiated by ataciguat in the presence of ODQ (p=0.0012). CONCLUSION: Ataciguat and zaprinast both have relaxing effects on sphincter of Oddi, although that of zaprinast is lower. We believe that ataciguat and zaprinast can be used in ERCP procedures in order to relax the sphincter of Oddi and thus can be used locally in order to decrease complications.

Serum anti-Müllerian hormone levels in euthyroid adolescent girls with Hashimoto's thyroiditis: relationship to antioxidant status.

OBJECTIVE: Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of Hashimoto's thyroiditis (HT), which is the most common thyroid disorder in adolescents. HT requires lifelong thyroid surveillance, particularly in women of childbearing age to avoid adverse effects on reproductive function. The aims of this study were to investigate serum concentrations of anti-Müllerian hormone (AMH), a marker of ovarian reserve, in euthyroid adolescent girls with newly diagnosed HT and explore the relationships between AMH levels and biomarkers of antioxidant status. STUDY DESIGN: We recruited 57 non-obese (body mass index [BMI] Z-score<2) adolescent girls with newly diagnosed HT and 50 age- and BMI-matched healthy controls for this case-control study. All participants were euthyroid. Hormonal and metabolic parameters, serum levels of AMH, and antioxidant status [paraoxonase (PON) and arylesterase (ARE) activities] were assessed. RESULTS: Serum AMH levels were significantly higher and serum PON and ARE activities were significantly lower in adolescents with HT than in the controls (p<0.001 for all). No significant associations were detected between the AMH level and any of the clinical or biochemical parameters in the control group. Serum AMH levels were negatively correlated with PON (r=-0.435, p=0.001) and ARE (r=-0.422, p=0.001) activities in adolescents with HT. CONCLUSION: The AMH level was significantly higher while the PON and ARE activities were significantly lower in euthyroid adolescent girls with newly diagnosed HT.

Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid.

BACKGROUND: Diagnosing cobalamin deficiency is critical, given the high prevalence of cobalamin deficiency particularly in developing countries. Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other words its specificity and sensitivity are low. The present study investigated the changes in the levels of metabolic markers - plasma homocysteine, plasma methylmalonic acid (MMA) and urinary MMA - of cobalamin metabolism. METHODS: Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from umbilical cord blood and urinary MMA in newborns were studied. RESULTS: Plasma cobalamin values were low in 66% of the mothers. There was a positive correlation between maternal and neonatal plasma cobalamin values (r = 0.72, p < 0.001). B12 was strongly inversely associated with plasma MMA, urine MMA and plasma homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA, urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA, urinary MMA and plasma homocysteine levels, respectively. CONCLUSION: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.

Do antithyroid antibodies affect hearing outcomes in patients with pediatric euthyroid Hashimoto's thyroiditis?

OBJECTIVES: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease in children. HT is a multifaceted disease with a variable clinicopathological presentation, including hearing impairment. It is known that hearing function is negatively affected in patients with thyroid disorders. The literature includes a very limited number of studies on hearing function in euthyroid pediatric patients with HT. The aim of this study was to determine the relationship between cochlear function and HT, independent of thyroid function. MATERIALS AND METHODS: The study included 48 children and adolescents (42 females and 6 males) aged 9-18 years that were diagnosed as HT, and 30 gender- and age-matched healthy controls. Hearing was assessed via otoscopy, tympanometry, pure-tone audiometry, and measurement of distortion product otoacoustic emissions. RESULTS: There weren't any significant differences in pure tone thresholds between the 2 groups based on pure-tone audiometry, except in the right ear at 6kHz and 8kHz. Distortion product otoacoustic emissions signal to noise ratios were significantly lower in the HT group than in the control group at 4 different frequencies (6kHz [left ear], 8kHz [left ear], 1.5kHz [right ear], and 6kHz [right ear]) (P<0.05). The signal to noise ratios at all frequencies were <6dB in 3% of left ears and 2.5% of right ears in the control group, versus 12.5% of left ears and 9.6% of right ears in the HT group. Distortion product amplitudes were significantly lower in the HT group than in the control group for both left and right ears at 1kHz, 1.5kHz, 3kHz, and 8kHz, and at 2kHz for left ears only (P<0.05). CONCLUSIONS: The present findings show that cochlear function was lower in the HT group than in the control group. Accordingly, we think that hearing in patients with HT should be monitored periodically, even if their hearing thresholds are within normal limits. Thyroid autoimmunity appears to play an important role in a decrease in cochlear activity in pediatric HT patients.