Cigdem Binay

Prevalence of nonclassic congenital adrenal hyperplasia in Turkish children presenting with premature pubarche, hirsutism, or oligomenorrhoea.

Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum of CYP21A2 mutations in NCAH patients. Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL. Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous. Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent.

Clinical and Hormonal Features of a Male Adolescent with Congenital Isolated Follicle-Stimulating Hormone Deficiency

Aim: Our aim was to describe the clinical and genetic findings in an adolescent male with isolated follicle-stimulating hormone (FSH) deficiency and demonstrate the efficacy of recombinant human FSH (rhFSH) replacement in this case. Methods: A 14.5-year-old adolescent male was referred with normal pubertal development and small testes. Serum testosterone, FSH, and luteinising hormone (LH) were measured at baseline and after gonadotropin-releasing hormone (GnRH) stimulation. Testicular biopsy was performed, and rhFSH replacement was administered for 6 months. The patients FSHβ gene was amplified and sequenced. Results: Basal and GnRH-stimulated FSH levels were undetectable, in contrast with increased LH levels under both conditions. Histopathological investigation of a testicular biopsy specimen revealed a reduced number of Sertoli cells, the absence of germ cells, Leydig cell hyperplasia, and a thickened basement membrane in seminiferous tubules. The testicular size changed from 1 ml at baseline to 6 ml after 6 months of rhFSH replacement. Sequencing of the FSHβ gene exon 3 revealed a new missense mutation (c.364T>C, resulting in p.Cys122Arg) in a homozygous state in the patient; both parents and a sister carried the same mutation in a heterozygous state. We also compared our case with all similar cases published previously. Conclusion: We herein described an adolescent male with isolated FSH deficiency due to a novel FSHβ gene mutation associated with a prepubertal testes size and normal virilisation.

Serum Irisin and Oxytocin Levels as Predictors of Metabolic Parameters in Obese Children

Objective: Irisin and oxytocin can affect energy homeostasis and it has been suggested that they may play an important role in reducing obesity and diabetes. In this study, we aimed to determine the relationship between metabolic parameters (including irisin and oxytocin levels) and anthropometric parameters in obese children. Methods: Ninety obese children (mean age, 13.85±1.63 years) and 30 healthy controls (mean age, 14.32±1.58 years) were enrolled in this study. Anthropometric and laboratory parameters (glucose, insulin, lipid, oxytocin, and irisin levels) were analyzed. The serum irisin and oxytocin levels were measured by enzyme-linked immunosorbent assay. Bioelectrical impedance was used to determine body composition. Results: Irisin level was higher in the patients than in the controls (p=0.018), and this higher irisin level was correlated with increased systolic blood pressure, body mass index, waist/hip ratio, fat percentage, fat mass, glucose level, insulin level, and homeostasis model assessment of insulin resistance. Serum oxytocin level was significantly decreased in obese children compared to the controls (p=0.049). Also, among the 60 obese patients, oxytocin level was significantly lower in patients with than in those without metabolic syndrome (8.65±2.69 vs. 10.87±5.93 ng/L, respectively), while irisin levels were comparable (p=0.049 and p=0.104, respectively). There were no statistically significant relationships between oxytocin or irisin levels and lipid levels (p>0.05). Conclusion: Obese children had significantly higher irisin levels than the healthy controls. Additionally, this study shows for the first time that oxytocin level is significantly lower in obese compared with non-obese children and also lower in obese children with metabolic syndrome compared to those without.

Cellular Trace Element Changes in Type 1 Diabetes Patients.

Objective: Type 1 diabetes mellitus (T1DM) may lead to deficiencies in trace elements that have substantial functions in the human organism. Changes in serum magnesium (Mg), copper (Cu), and zinc (Zn) levels are correlated with metabolic control and diabetes complications. The aim of this study was to evaluate the intra-erythrocyte levels of trace elements and urinary Mg excretion following intravenous (iv) Mg tolerance testing in children with T1DM. Methods: A total of 43 children aged 2-18 years with T1DM and age/gender-matched 25 healthy children were included in the study. The iv Mg tolerance test was performed following the measurement of intra-erythrocyte Mg (eMg1), Cu (eCu1), and Zn (eZn1) levels using the atomic absorption spectrophotometer method. The Mg retention ratio was estimated from measurements in 24 h urine samples. Results: No statistically significant difference was found for eMg1, eCu1, and eZn1 levels between the patient and control groups (p>0.05). In the patient group, the eMg1, eCu1, and eZn1 levels measured after the iv Mg tolerance test significantly increased compared with the baseline levels (p<0.05), and the Mg excretion ratio measured from the urine collected after the iv MgSO4 infusion was >50%. Conclusion: The increased retention value following the iv Mg tolerance testing indicates intracellular Mg deficiency in children with T1DM.

Growth hormone and the risk of atherosclerosis in growth hormone-deficient children.

OBJECTIVE Growth hormone-deficient (GHD) children have been found to have higher cardiovascular mortality rates and an increased carotid intima-media thickness (CIMT). This study investigated the risk of atherosclerosis and the effect of recombinant growth hormone (rhGH) replacement therapy on the lipid profile and CIMT in GHD children. DESIGN A total of 40 GHD children (mean age: 12.3±2.04 years) were investigated before and after 1 year of rhGH therapy at a dosage of 0.03 mg/kg/day and 40 age- and sex-matched healthy children (mean age: 12.1±2.23 years) were enrolled as a control group, in the same pubertal stage. Fasting blood samples were obtained for lipid profile, IGF-1, and IGFBP-3 analyses. The patients and controls underwent CIMT measurements before and after 1 year of rhGH treatment. RESULTS The growth velocity and height standard deviation scores increased significantly over 1 year of treatment in all patients. The total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and atherogenic index (Ai) values were increased while the high-density lipoprotein (HDL) cholesterol value was decreased in the GHD children, as compared to the controls; however, the triglyceride (TG) level was comparable. After 1 year of treatment, a significant decrease in the TC, LDL cholesterol, and Ai values as well as a significant increase in the HDL value were observed in the GHD patients, with the values becoming similar to those in the control group. The mean CIMT was significantly greater in the GHD subjects than in the controls. After 1 year of therapy, the CIMT in the GHD subjects had decreased significantly; however, it was still greater than that in the control group. IGF-1 was negatively correlated with TC, LDL cholesterol, Ai, right CIMT, and left CIMT. CONCLUSIONS GHD is associated with increased atherosclerotic risk in children. An improved lipid profile and CIMT were detected after 1 year of hormone replacement therapy.

Gonadoblastoma and Papillary Tubal Hyperplasia in Ovotesticular Disorder of Sexual Development.

Ovotesticular disorder of sexual development (DSD), formerly known as true hermaphroditism, is a rare form of DSD in which both testicular and ovarian tissues are present in the same individual either in a single gonad (ovotestis) or in opposite gonads with a testis and an ovary on each side. The diagnosis of ovotesticular DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous. Herein, we report two patients with ovotesticular DSD-one presenting with ambiguous genitalia on the third day after birth and the other with short stature and primary amenorrhea in adolescence. Clinical and histopathological investigation revealed a sex-determining region on the Y chromosome (SRY)-positive 46,XX karyotype and bilateral ovotestes in case 1 and a 46,XY karyotype with hypergonadotropic hypogonadism and a streak gonad in one ovotestis with dysgerminoma, gonadoblastoma, and papillary tubal hyperplasia in the contralateral ovotestis in case 2. Laparoscopic examination and gonadal biopsy for histopathological diagnosis remain the cornerstones for a diagnosis of ovotesticular DSD. Moreover, SRY positivity in a 46,XX patient, a 46,XY karyotype, an intra-abdominal gonad, and the age of patient at the time of diagnosis are predictive risk factors for the development of gonadoblastoma and/or dysgerminoma in ovotesticular DSD.

The correlation between GnRH stimulation testing and obstetric ultrasonographic parameters in precocious puberty

Abstract The aim of this study was to determine reliable cut-off levels of basal gonadotropin and to assess the correlation of obstetric ultrasound parameters with the GnRH stimulation test. The GnRH stimulation test was performed in a cohort of young female patients who presented at our hospital for the evaluation of early signs of puberty. Using receiver operating curves (ROCs), the sensitivity and specificity of basal luteinising hormone (LH), follicle stimulating hormone (FSH), basal and stimulated LH/FSH ratio, oestradiol levels and ultrasonographic parameters were evaluated at each level, and the area under curve (AUC) was measured. One hundred female children were assessed. We found that LH levels, peak LH/FSH ratio, fundal/cervical ratio, uterus length, and ovarian volume were reliable predictors of central precocious puberty (CPP). Cut-off levels of basal LH and the peak LH/FSH ratio had high specificity in our cohort. In addition, obstetric ultrasound parameters represent reliable predictors for the diagnosis of CPP.

The earlier described mutation (c.307C>T [p.R103X]) in the SRD5A2 gene causing a 46,XY female phenotype

Abstract Deletions and mutations in the 5-α-reductase type 2 (SRD5A2) gene have been identified in 46,XY disorders of sexual differentiation (DSD). The clinical spectrum is heterogeneous, varying from a normal female external genital appearance to clitoromegaly and isolated micropenis or microphallus associated with hypospadias of various degrees. We describe a 46,XY DSD patient with a homozygous c.307C>T (p.R103X) mutation in the SRD5A2gene. The case presented with a normal female external genital phenotype.

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

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

Horner Syndrome Secondary to Thyroid Surgery

Horner syndrome (HS), caused by an interruption in the oculosympathetic pathway, is characterised by myosis, ipsilateral blepharoptosis, enophthalmos, facial anhydrosis, and vascular dilation of the lateral part of the face. HS is a rare complication of thyroidectomy. A 15-year-old female patient presented with solitary solid and large nodule in the right thyroid lobe. Ultrasound-guided fine-needle aspiration was performed and the cytological examination results were undefined. The patient underwent a total thyroidectomy. On postoperative day 2, she developed right-sided myosis and upper eyelid ptosis. HS was diagnosed. Interestingly, the patient exhibited an incomplete clinical syndrome with the absence of vasomotor symptoms. We herein report a case of HS in a 15-year-old female patient after total thyroidectomy. The possible causes of HS were ischaemia-induced nerve damage and stretching of the cervical sympathetic chain by the retractor during thyroidectomy. Clinicians should be aware of the possibility of this rare but important surgical complication.