Mesut Parlak

Investigation of endothelial dysfunction and arterial stiffness in children with type 1 diabetes mellitus and the association with diastolic dysfunction

Objective: The objective of this study is to investigate endothelial dysfunction (ED) and arterial stiffness (AS) and determine the association with diastolic dysfunction in children with type 1 diabetes mellitus (DM). Methods: A total of 42 patients without diabetic complications (mean age: 13.21 years) and 40 healthy (mean age: 13.07 years) children were included in this study. AS was assessed with ascending aorta M-mode measurements, diastolic dysfunction with pulsed wave (PW) Doppler and tissue Doppler echocardiography measurements and flow-mediated dilatation (FMD) and carotid intima–media thickness (CIMT) with high-resolution ultrasonography. Results: Results of diabetic group and healthy children were compared. In diabetic group, aortic strain (8.40 ± 2.98, 20.12 ± 5.04; p < 0.001), aortic distensibility (7.36 ± 2.92, 16.59 ± 4.25; p < 0.001) and FMD% (7.70 ± 2.83, 11.33 ± 2.85; p < 0.001) were found decreased, and CIMT (0.52 ± 0.09 mm, 0.47 ± 0.08 mm; p < 0.05) was found increased. Additionally, left ventricular lateral segment and right ventricular free-wall isovolumic relaxation time (IVRT) and myocardial performance index (MPI) were found increased. Correlation analyses demonstrated a negative correlation between FMD and IVRT and MPI. Conclusions: ED and AS were found in type 1 DM patients without diabetic complications. Additionally, correlation was shown between increased AS and ED and right and left ventricular diastolic dysfunctions.

Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report

Abstract Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

A Combination of Nifedipine and Octreotide Treatment in an Hyperinsulinemic Hypoglycemic Infant

Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the pancreatic beta cell, are identified in approximately 50% of these patients. The first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can be used in patients who show no response to diazoxide. Nifedipine, a calcium-channel blocker, has been shown to be an effective treatment in a small number of patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months of age due to a lack of response to diazoxide and octreotide treatment. Severe hypoglycemic attacks continued following surgery, while the patient was being treated with octreotide. These attacks resolved when nifedipine was introduced. Whilst our patient responded well to nifedipine, the dosage could not be increased to 0.75 mg/kg/day due to development of hypotension, a reported side effect of this drug. Currently, our patient, now aged 4 years, is receiving a combination of nifedipine and octreotide treatment. He is under good control and shows no side effects. In conclusion, nifedipine treatment can be started in patients with HH who show a poor response to diazoxide and octreotide treatment.

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 Hashimotos 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.

Try235Phe homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Turkish patient.

Steroid 5-a reductase type 2 isoenzyme (SRD5A2) deficiency is a male-limited autosomal recessive disorder that results in decreased conversion of testosterone to dihydrotestosterone with various degree of incomplete virilization in affected 46, XY infants. No clear genotype-phenotype relationship has been reported till date; moreover, the same mutation can result in considerable heterogeneity in clinical manifestations. Of 6 documented cases with Try235Phe homozygous mutation of the SRD5A2 gene, 3 patients had predominantly female external genitalia whereas the other 3 had predominantly male phenotype. We report Try235Phe homozygous mutation of the SRD5A2 gene in a Turkish patient who was initially assigned as a girl because of the predominantly female appearance of the external genitalia.

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

Abstract 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.

High-Dose Hook Effect in 17-Hydroxyprogesterone Assay in a Patient with 21-Hydroxylase Deficiency.

Congenital adrenal hyperplasia (CAH) describes a group of disorders characterized by enzyme defects in adrenal steroidogenesis. 21-hydroxylase deficiency (21-OHD) is the most commonly encountered form. The analysis of steroids in pediatric cases requires high-sensitivity assays. A 14-year-old Syrian girl was referred for evaluation of short stature, amenorrhea, and hirsutism. On physical examination, breast development was Tanner stage 1. She had a phallic clitoris with a single urogenital orifice. Laboratory findings revealed primary adrenal deficiency with high androgen levels and low levels of 17-hydroxyprogesterone (17-OHP), (<0.05 ng/mL) and estrogen. This unexpected result led to suspicion of a high-dose hook effect. The measurement was repeated after 1/10 dilution of serum, and a high level of 17-OHP (115.4 ng/mL) was detected with the same test-enzyme-linked immunosorbent assay (ELISA). Simple virilizing form of CAH (21-OHD) was suspected and confirmed with genetic analysis. After initiation of glucocorticoid therapy, breast development was noted along with a decrease in testosterone level and an increase in estrogen level. To our knowledge, this is the first case report of hook effect for 17-OHP immunoassay in a patient with 21-OHD. High-dose hook effect should be suspected in patients with CAH when the test results are incompatible with one another. Additionally, this case demonstrates that a high testosterone level can block aromatase activity and consequently also estrogen production and breast development.

Basal Serum Neurokinin B Level can be used to Differentiate Idiopathic Central Precocious Puberty from Premature Thelarche in Girls.

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.

Clinical expression of familial Williams-Beuren syndrome in a Turkish family.

Abstract Williams-Beuren syndrome (WBS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability with a typical neurobehavioral profile, cardiovascular anomalies, and occasional infantile hypercalcemia. Majority of cases occur sporadically, and only a few cases of familial WBS have been reported. Although pre- and post-natal growth retardation is a common clinical feature of the syndrome, growth hormone deficiency is detected only in a few patients. To our knowledge, there has only been one report about familial Williams-Beuren syndrome in the Turkish population. Here, we report on the three molecular cytogenetically confirmed familial Williams-Beuren syndromes detected in a family with familial short stature. The father, daughter, and son analyzed with clinical and laboratory findings, and reasons of the short stature in Williams-Beuren syndrome are discussed through the literature.

Evaluation of Behavioral Disorders in Children and Adolescents with Short Stature

Aim: The aim of this study was to evaluate the behavioral disorders in children and adolescents diagnosed with short stature. Materials and Methods: The study included the patients presented to the pediatrics and the pediatric endocrinology clinics between December 2012-April 2013. A hundred patients diagnosed with short stature were assigned into the patient group and 100 patients with normal stature were assigned into the control group. Informed consents were obtained from the patients and their families. The participants were administered the DSM-IV based Disruptive Behavioral Disorders Screening and Rating Scale and a questionnaire composed of questions about socio-demographic features. p <0.05 was considered significant. Results: The mean age of the control group and the patient group was 11.67±2.04 years and 11.86±2.63 years, respectively. The groups were similar in terms of the mean age (p=0.356) and gender (p=0.322). The patient group got 6.27±6.01 for the attention deficit subscale, 6.58±5.18 for the hyperactivity subscale, 5.68±4.85 for the oppositional- defiant subscale and 1.59±3.18 for the behavioral scale (mean scores). The control group received 5.64±4.64 for the attention-deficit subscale, 5.30±4.88 for the hyperactivity subscale, 4.55±4.32 for the oppositional-defiant subscale