Omer Tarim

Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus.

Abstract Background: The relationship between hemoglobin A1c (HbA1c) and iron status in type 1 diabetes mellitus (DM) has not been adequately studied. In this prospective investigation, we aimed to determine the effect of iron deficiency on HbA1c in diabetic patients who also had insufficient iron stores.

Rare Causes of Primary Adrenal Insufficiency: Genetic and Clinical Characterization of a Large Nationwide Cohort

Context: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0–18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c.IVS3ds+1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.

Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism.

Objective  Nonsyndromic autosomal recessively inherited nongoitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2‐5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG.

Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).

Testicular Adrenal Rest Tumors in Patients with Congenital Adrenal Hyperplasia

Objective: Early diagnosis and treatment of testicular adrenal rest tumors (TART) is important for gonadal functions and fertility protection in boys with congenital adrenal hyperplasia (CAH). In this descriptive study, we investigated the prevalence of TART in boys with 21-hydroxylase deficient (21OHD) CAH followed in our pediatric endocrine clinic. Methods: The study group consisted of 14 male patients with a mean age of 9.6±5.1 (range: 0.8-18.3) years. Six (42.9%) of the 14 patients were diagnosed as having salt-wasting type (SW) and eight (57.1%) patients - as having the simple virilizing (SV) form of 21OHD. Mean age at diagnosis was 2.9±2.7 (range: 0.03-6.3) years. Two different radiologists performed scrotal ultrasonography. Chronological age, bone age, and anthropometric measurements were evaluated. Serum adrenocorticotropic hormone (ACTH), 17-alpha-hydroxyprogesterone (17OHP) and androstenedione levels were also evaluated in all patients during the follow-up period. Results: Scrotal ultrasonography revealed bilateral TART in two patients (14.3%) and testicular microlithiasis (TM) in four patients (28.6%). One patient had both TART and TM bilaterally. During the follow-up period, the mean serum adrenocorticotropic hormone, 17OHP and androstenedione levels in the total group of patients were 130.0±179.1 pg/mL (21.7-726.5), 5.8±3.3 ng/mL (0.8-11.4) and 4.3±4.1 (0.2-11.0) ng/mL, respectively. Conclusions: Microlithiasis or TART may be frequently encountered during the follow-up of patients with CAH. In order to prevent late complications including infertility, we suggest that ultrasonographic evaluations be performed yearly in all male CAH patients. Conflict of interest:None declared.

Thyroid Hormones and Growth in Health and Disease

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared.

Increased incidence of congenital hypothyroidism due to iodine deficiency.

Background: The incidence of congenital hypothyroidism (CH) is expected to be elevated in iodine‐deficient areas. In this study, the authors aimed to determine the incidence of transient and permanent CH in a large city which is known to be in the zone of moderate iodine deficiency.

TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis.

Abstract Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multicase families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.

Prevalence and correlates of obesity in schoolchildren from the city of Bursa, Turkey.

Background and objectives: The prevalence of childhood obesity has been dramatically increasing worldwide. This study was performed to examine the prevalence and etiological factors of obesity in children aged 6−12 years and to investigate the relative contribution of exogenous factors with respect to sociodemographic data. Methods: A total of 5368 children aged 6−12 years in eight urban elementary schools located in Bursa, the fourth largest city of Turkey, were included in this cross−sectional study. A dietary record for three days and a questionnaire for the assessment of socio−economic and demographic parameters were completed by the parents at home. The height and weight of the children were measured and relative weight and body mass index (BMI) were calculated. Results: The prevalence of overweight, obesity and severe obesity according to BMI were 12.4%, 7.8% and 2.2%, respectively. The female/male ratio among obese children was 1.24. Eighty percent of obese children had one or both parents obese. Age, gender, presence of obesity in parents, higher educational level of the parents, consumption of soft beverages such as soda and juice, physical activity level and higher income of the family were found as the contributing factors to obesity. Conclusion: The prevalence of obesity is increasing in Turkey in parallel to the trend in many countries. There are consistent and predictable sociodemographic parameters that are associated with or may impose a risk factor for obesity. Identification of these risk factors will provide areas to target in the prevention and management of this common problem. Conflict of interest:None declared.

A Rare Cause of Precocious Puberty: Hepatoblastoma

Hepatoblastoma, an embryonal tumor, is one of the most common primary liver tumors in childhood. It secretes human chorionic gonadotropin (hCG), which can cause precocious puberty (PP). Herein, we present a case with PP who had enlarged penile size noticed during a diagnosis of hepatoblastoma. Laboratory examination revealed increased testosterone, alpha-fetoprotein (AFP), and hCG levels. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were within prepubertal ranges. The diagnosis of hepatoblastoma was made by liver biopsy. Chemotherapy was administered, and the patient was referred to surgery. Ten months later, testis volumes were below 4 ml bilaterally, and penile length was 5.5 cm. Serum testosterone, AFP, and hCG levels decreased. Resection of the tumor and chemotherapy are essential for the treatment of hepatoblastoma and they can eliminate the symptoms of PP. Conflict of interest:None declared.