Atilla Büyükgebiz

Newborn screening for congenital hypothyroidism.

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.

The frequency of vitamin D insufficiency in healthy female adolescents

Aim: To establish the frequency and causes of vitamin D insufficiency in healthy female adolescents in Izmir, Turkey. Methods: 64 adolescents from a low‐ (Ikinci Inönü) and a high‐ (Ilica) socio‐economic settlement were included. Parents’ monthly income was classified as low, middle and high. The blood samples were drawn at the end of the summer and winter periods. Results: Vitamin D insufficiency percentages for the end‐of‐winter period were 59.4% in Ikinci Inönü and 15.6% in Ilica, and for the end of summer 25% and 15.6%, respectively. Calcidiol levels of cases from Ikinci Inönü were found to be lower compared with the levels of cases from Ilica (34±15 vs 59±24 nmol/l for end of winter, p= 0.000; 51±22 vs 65±28 nmol/l for end of summer, p= 0.03). Calcidiol levels of cases whose parental monthly income was low and whose mothers were illiterate were significantly lower than the others (48±18 vs 65±29 nmol/l for end of summer, p= 0.01; 33±16 vs 56±23 nmol/l for end of winter, p= 0.000; 45±13 vs 64±29 nmol/l for end of summer, p= 0.007; 36±17 vs 51±25 nmol/l for end of winter, p= 0.02; respectively).

The Ped-APS Registry: the antiphospholipid syndrome in childhood

In recent years, antiphospholipid syndrome (APS) has been increasingly recognised in various paediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way. The project of an international registry of paediatric patients with APS (the Ped-APS Registry) was initiated in 2004 to foster and conduct multicentre, controlled studies with large number of paediatric APS patients. The Ped-APS Registry is organised as a collaborative project of the European Forum on Antiphospholipid Antibodies and Juvenile Systemic Lupus Erythematosus Working Group of the Paediatric Rheumatology European Society. Currently, it documents a standardised clinical, laboratory and therapeutic data of 133 children with antiphospholipid antibodies (aPL)-related thrombosis from 14 countries. The priority projects for future research of the Ped-APS Registry include prospective enrolment of new patients with aPL-related thrombosis, assessment of differences between the paediatric and adult APS, evaluation of proinflammatory genotype as a risk factor for APS manifestations in childhood and evaluation of patients with isolated nonthrombotic aPL-related manifestations.

Fetal and neonatal endocrine disruptors.

Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures. Conflict of interest:None declared.

Hepatic glycogenosis: a rare cause of hepatomegaly in Type 1 diabetes mellitus

Hepatomegaly, with or without abnormal liver function tests, was a common feature of both pediatric and adult patients with diabetes mellitus. We are reporting a case of a 16-year-old diabetic boy in whom we found hepatomegaly, mildly elevated transaminases and elevated serum lipids never noticed before. Abdominal ultrasound confirmed hepatomegaly; liver biopsy pointed out a picture compatible with glycogenosis. The patients abnormal liver function tests, elevated serum lipids and hepatomegaly decreased over a period of 4 weeks with tight metabolic control. This situation was due to overinsulinization because the patient assumed an excessive quantity of food and therefore took an excessive quantity of insulin. In conclusion, hepatomegaly may be seen in diabetic patients due to hepatic glycogen accumulation as a result of excessive food and insulin consumption. In hepatic glycogenosis, the pathological findings improve in 4 weeks when good metabolic control is provided. Therefore, the other reasons must be investigated when hepatomegaly persists for a longer period.

Leptin levels in boys with pubertal gynecomastia

BACKGROUND It has been reported that there is a relationship between circulating leptin and sex steroid hormones and leptin is able to stimulate estrogen secretion by increasing aromatase activity in adipose stromal cells and breast tissue. Leptin receptors have been also shown in mammary epithelial cells and it has been suggested that leptin is involved in the control of the proliferation of both normal and malignant breast cells. AIM To investigate circulating leptin levels in boys with pubertal gynecomastia. METHODS Twenty boys with pubertal gynecomastia who were in early puberty and had no obesity, and 20 healthy individuals matched for age, pubertal stage and body mass index (BMI) with the study group, were enrolled in the study. Body weight, height and left midarm circumference (MAC) and left arm triceps skinfold thickness (TSF) were measured and BMI was calculated. A fasting blood sample was collected and routine hormonal parameters including prolactin, beta-human chorionic gonadotropin (betaHCG), total and free testosterone, estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, androstenedione (AS) and dehydroepiandrosterone sulfate (DHEAS) levels were studied. Serum leptin levels were analyzed using radioimmunoassay. RESULTS The mean ages of the study and control group were not different (13.9 +/- 0.89 and 14.2 +/- 0.66, respectively). No significant difference was found for BMI, MAC and TSF values between the two groups. There was no significant difference for hormonal parameters including FSH, LH, total and free testosterone, estradiol, AS, DHEAS and estradiol/total testosterone ratio between boys with pubertal gynecomastia and the controls. Serum leptin levels were found significantly higher in the study group compared with the healthy controls (5.58 +/- 0.81 and 2.39 +/- 0.29 ng/ml, respectively; p <0.001). No correlation could be determined between serum leptin levels and hormonal parameters. CONCLUSION The presence of higher leptin levels in boys with pubertal gynecomastia indicates that leptin may be involved in the pathogenesis of pubertal gynecomastia. The role of circulating leptin in pubertal gynecomastia is probably related to increase in estrogen and/or estrogen/ androgen ratio by the stimulating effect of leptin on aromatase enzyme activity in both adipose and breast tissues, or a direct growth stimulating effect of leptin on mammary epithelial cells, or increase in sensitivity of breast epithelial cells to estrogen with inducing functional activation of estrogen receptors by leptin in breast tissue.

Effects of Growth Hormone on Growth, Insulin Resistance and Related Hormones (Ghrelin, Leptin and Adiponectin) in Turner Syndrome

Background:Concomitant evaluation of the metabolic and growth-promoting effects of growth hormone (GH) therapy in Turner syndrome (TS) may be used in the prediction of the growth response to GH therapy. Aim: To evaluate the metabolic effects of GH therapy in TS and correlation with the short-term growth response. Patients: 24 prepubertal children with TS, aged 9.4 ± 2.6 years were followed for auxology and IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, lipids and OGTT results in a prospective multicenter study. Intervention: GH (Genotropin®) in a dose of 50 µg/kg/day for 1 year. Results: Height standard deviation score (SDS) increased from –3.9 ± 1.5 to –3.5 ± 1.4 (p = 0.000) on therapy. BMI did not change. IGF-I SDS increased from –2.3 ± 0.4 to –1.6 ± 1.1 at 3 and 6 months (p = 0.001) and decreased thereafter. Serum leptin decreased significantly from 2.3 ± 3.9 to 1.7 ± 5.3 ng/ml (p = 0.022) at 3 months and increased afterwards. Serum ghrelin decreased from 1.2 ± 0.8 to 0.9 ± 0.4 ng/ml (p = 0.005) with no change in adiponectin. Basal and stimulated insulin levels also increased significantly. Δ height SDS over 1 year showed a significant correlation with Δ IGF-I0–3 months (r = 0.450, p = 0.027). Conclusion: IGF-I may be considered as a marker of growth response in TS at short term. Leptin shows a decrease at short term but does not have a correlation with growth response. The decrease in ghrelin in face of unchanged weight seems to be associated with increase in IGF-I and insulin levels. The unchanged adiponectin levels in spite of an increase in insulin levels indicates that adiponectin is mainly affected by weight, not insulin.

Factors influencing remission phase in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (DM) is characterized by selective and progressive autoimmune destruction of beta-cells of the pancreas in genetically susceptible individuals. This autoimmune process takes years before the patient eventually develops clinical DM. Over the course of the disease, some patients regain their ability to secrete endogenous insulin to some extent for a period of few months to years. This partial remission phase has drawn a lot of attention since it offers a window of opportunity to intervene in an attempt to restore pancreatic beta-cell function or to prevent development of the disease in the prediabetic population at risk. Several factors, including age, sex, pubertal status, metabolic findings at the time of presentation, HLA types, presence of diabetes-associated autoantibodies, have been recognized to affect the likelihood of partial or complete remission in children with type 1 DM. Several interventions in patients with new-onset type 1 DM have been tried, including oral nicotinamide and immunomodulatory and immunosuppressive treatments, in an attempt to preserve beta-cell function and to promote or prolong the remission phase, but no conclusive data have been obtained so far. This review summarizes current knowledge on the factors that possibly influence the remission phase in children with type 1 DM.

BILATERAL BREAST MASSES AND BLOODY NIPPLE DISCHARGE IN A TWO YEAR-OLD BOY

Breast enlargement with bloody discharge is very rare in childhood. We report a two year-old boy with breast enlargement and bloody discharge. Because of persistent bloody discharge, subcutaneous mastectomy was performed. The specimen showed histologic changes identical to those seen in adult mammary duct ectasia. We suggested that the infants own endocrine system is responsible for breast enlargement and mammary duct ectasia, possibly occurring as a result of a mechanism similar to that in adults.

Helicobacter pylori infection in children with constitutional delay of growth and puberty.

Helicobacter pylori is a gastroduodenal pathogen strongly associated with chronic gastritis and duodenal ulceration. It is thought that H. pylori infection might be one of the causes of growth retardation in children. The aim of this study was to evaluate the seroprevalence of H. pylori in children with constitutional delay of growth and puberty (CDGP). H. pylori seropositivity was studied in 24 children with CDGP (22 M, 2 F) and 32 healthy age-matched children with normal pubertal development. Mean age of the children with CDGP was 14.53 +/- 1.12 yr and all of them had been diagnosed as CDGP after physical and laboratory assessment. H. pylori IgG positivity was detected in 16 of the 24 children with CDGP (66.6%) and 12 of 32 controls (37.5%) (p <0.05). This finding is consistent with the hypothesis that H. pylori infection could be one of the environmental factors causing CDGP.