Uncoupling protein gene UCP1-3826A/G, UCP2 Ins/Del and UCP3-55C/T polymorphisms in obese Turkish children.

BACKGROUND: Mitochondrial uncoupling proteins (UCP) 1, 2 and 3 are members of the anion carrier protein family located in the inner mitochondrial membrane. There are various controversial reports on UCP genotypes and obesity in adults and children. This study aims to investigate the link between mostly studied UCP polymorphisms (UCP1-3826A/G, UCP2 Insertion/Deletion (Ins/Del) polymorphism of exon 8, and UCP3-55C/T Polymorphisms) and obesity in Turkish children. Furthermore, the relationships of UCP polymorphisms are also analyzed within the scope of metabolic parameters of obese children. METHODS: Molecular screening of the UCP1, UCP2, and UCP3 gene polymorphisms was carried out in 189 children aged 6 to 18 years, 102 of who had exogenous obesity (54 girls) and 87 of whom were healthy controls (48 girls). In the obese group, fasting lipids, glucose and insulin levels were measured. In 60 obese children, an oral glucose tolerance test (OGTT) was performed with 0, 30, 60, 90 and 120 minutes of sampling for plasma glucose and insulin levels. RESULTS: The frequency of UCP polymorphisms was similar in obese and non-obese children. In obese children, fasting lipids, glucose and insulin levels were not different among the UCP 1, 2 and 3 genotypes. While no relationship was found between the UCP 1 and 3 genotypes and glucose/insulin levels during OGTT, carriers of the Insertion allele with UCP2 Ins/Del polymorphism had significantly higher 30-minute insulin levels (p=0.018). CONCLUSIONS: Polymorphisms of the UCP1-3826A/G, UCP2 Ins/Del, and UCP3-55C/T are not associated with obesity and related pathologies in Turkish children. However, the presence of the Ins allele of the UCP2 gene has been found to have an unfavorable influence on early insulin excursion after glucose loading.

AMH levels at central precocious puberty and premature thelarche: is it a parameter?

BACKGROUND: The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated. OBJECTIVE/HYPOTHESIS: By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset. SUBJECTS: Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study. METHODS: The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups. RESULTS: The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022). CONCLUSION: These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

Neonatal thyrotoxicosis with severe supraventricular tachycardia: case report and review of the literature.

Neonatal thyrotoxicosis is a rare condition caused by the transplacental passage of thyroid stimulating immunoglobulins from mothers with Graves' disease. We report a case of neonatal thyrotoxicosis with concurrent supraventricular tachycardia (SVT). The female infant, who was born by section due to breech delivery and meconium in the amniotic fluid at 36 weeks of gestation, presented with tachycardia on day 7. Her heart rate was between 260 and 300 beats/min, and an electrocardiogram revealed ongoing SVT. Sotalol was effective after two cardioversions in maintaining sinus rhythm. Thyroid function studies revealed hyperthyroidism in the infant, and her mother was found to have Graves' disease. Since symptoms and signs can vary, especially in preterm infants with neonatal hyperthyroidism, we want to emphasize the importance of prenatal care and follow-ups of Graves' disease associated pregnancies and management of newborns after birth.

Congenital hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene.

Congenital hyperinsulinism is the most frequent cause of persistent hypoglycemia in infancy. We present the case of a preterm, large-for-gestation-age infant with congenital hyperinsulinism who was found to have a novel p.Q392H homozygous mutation in the ABCC8 gene. The patient had severe brain damage, despite early diagnosis and appropriate management. The new mutations may provide an understanding of the prognosis and treatment of the disease. In addition, the data will help the family make informed decisions about future pregnancies.

Abdominal aorta intima media thickness in obese children.

The aim of this study is to investigate whether abdominal aorta intima media thickness (aIMT), increases in obese children and to determine risk factors. Ninety-six children aged 5-16 (51 obese and 45 non-obese) were enrolled in this prospective and cross-sectional study. Age, gender, and relative body mass index (BMI) were recorded. Their serum lipids, thyrotropin, fasting glucose and insulin levels were analyzed. The homeostasis model assessment (HOMA-IR) score was calculated for insulin resistance. Anthropometric and biochemical data were assessed along with aIMT. Findings in obese children were compared with those of non-obese control subjects. The aIMT was significantly greater in obese children. Similar trends were observed in both prepubertal children and adolescents. In obese children, the mean aIMT (mm) was 0.021 (years of age) +0.519. In non-obese children, the mean aIMT (mm) was 0.017 (years of age) +0.381. Our data suggests a relationship between glucose metabolism and aIMT in obese children. BMI was an independent risk factor for increasing aIMT. In conclusion, when compared with non-obese controls, obese children demonstrated significantly increased aIMT. Higher BMI, insulin, HOMA-IR and increased systolic blood pressure seem to be the main factors contributing to increased aIMT and risk for developing vascular disease. Childhood obesity contributes to the development of an increased aIMT.

Cushing syndrome related to leukemic infiltration of the central nervous system: a case report and a possible role of LIF.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS) in the presence of leukemic central nervous system infiltration is very rare. CASE: A 3.8-year-old girl who had been treated for B-cell acute lymphoblastic leukemia (ALL) for 1.5 years was admitted to our hospital with excessive weight gain and depression for the last 2 months. Prior to her admission, she was on maintenance with the ALL-BFM95 study protocol for 10 months that does not contain corticosteroids. On physical examination, central obesity and moon face appearance were determined. Laboratory tests revealed high morning ACTH, cortisol level, and 24-h urinary free cortisol level. Morning cortisol level was 33.94 nmol/L after a 2-day (4 × 0.5 mg) dexamethasone suppression test. A lumbar puncture revealed leukemic cells in the cerebrospinal fluid. No pituitary adenoma was detected on magnetic resonance imaging. We diagnosed the patient with ACTH-dependent CS related to leukemic infiltration of the central nervous system. CONCLUSION: Central nervous system infiltration should be considered in leukemic patients who have developed CS. We believe increased leukemia inhibitory factor levels may be a factor for CS in our patient with ALL.

OGTT results in obese adolescents with normal HOMA-IR values.

OBJECTIVE: To investigate insulin resistance (IR) with OGTT in obese adolescents who have normal fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR). SUBJECTS: A total of 97 obese adolescents who had values of HOMA-IR <3.16 and insulin levels <18 µU/mL (125 pmol/L) were included in the study. METHODS: Oral glucose tolerance test (OGTT) was performed on all cases. Subjects were divided into two groups: subjects with and without IR using an insulin peak of ≥150 µU/mL (1041.8 pmol/L) and/or ≥75 µU/mL (520.9 pmol/L) 120 min after glucose charge and the sum of insulin levels >2083.5 pmol/L (300 µU/mL) in OGTT. IR risk factors were defined as family history of diabetes mellitus, acanthosis nigricans (AN), and hepatic steatosis. RESULTS: IR was detected in 61 (62.9%) patients. The IR group had significantly more frequent AN (p=0.0001). As the number of risk factors increased, the frequency of IR also increased (p=0.01). CONCLUSION: We advise to perform OGTT in obese adolescents with normal HOMA-IR, if they have risk factors for IR.

Hyperprolactinemia as a rare cause of hypertension in chronic renal failure.

Chronic renal failure (CRF) is associated with a high risk for hypertension. An individualized treatment should be initiated after the diagnosis of hypertension and underlying etiology. Many metabolic and endocrinal abnormalities are encountered in CRF. We present an 11-year-old boy with CRF developing galactorrhea and hyperprolactinemia associated with α-methyldopa, defective dopaminergic control, and resistance to multi-antihypertensive therapy. Cabergoline, a dopamine receptor agonist, was effectively used in the treatment of hypertension. It is important to remember that sometimes treatment of an illness becomes the cause of this illness.

The effect of corrective surgery on serum IGF-1, IGFBP-3 levels and growth in children with congenital heart disease.

The aim of this study is to evaluate growth and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in infants with congenital heart disease (CHD) pre- and postoperatively over a period of a year. Anthropometric values and serum levels of IGF-1 and IGFBP-3 of 40 infants with CHD (20 cyanotic and 20 acyanotic) were compared with 32 healthy controls. Acyanotic infants and infants with pulmonary hypertension (PH) presented significantly more growth failure. Preoperatively, serum IGF-1 and IGFBP-3 levels were lower in the acyanotic group than the cyanotic and the control groups (p = 0.22; p < 0.01). The upward trend in IGF-1 and IGFBP-3 levels in this year-long study demonstrated that the values in the third month and the first year were higher than the preoperative values (p < 0.05). The parallel increase of weight gain and IGF-1, IGFBP-3 levels were the best evidence that these parameters are good nutritional indicators. Timing the corrective surgery before chronic malnutrition or PH develops is an important issue to maintain a normal growth for children with CHD.

Diagnosis of a trend towards obesity in preschool children: a longitudinal study.

The study was planned to determine identifiable starting points of a trend towards obesity and the influence of variables in preschool children aged 0 to 6 years. In this longitudinal follow-up study, 102 children were enrolled. Anthropometric measurements such as weight-height centiles (specific for gender and age group), weight-height growth velocities, and body mass indices were taken annually and compared within each group from birth to 6 years. Family history and lifestyle variables were also recorded and compared. Our study has shown that gender does not affect the trend towards obesity. In obese children, the earliest sign of a trend was the rapid increase of weight and weight gain velocity after 6 months. There were upward trends in the BMI values indicating obesity at 1 year of age in boys and at 6 months of age in girls. The height was higher in obese children than in non-obese ones after 4 years of age. Paternal obesity and having an obese sibling were significant risk factors for obesity. In conclusion, 6 months are considered to be the most critical periods for evaluating the development of obesity in childhood. The efforts for preventing obesity should be initiated at 6 months of age.

PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children.

Obesity is associated with the changes of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNFalpha) and transforming growth factor beta (TGFbeta) levels. However, the precise effect of the 4G allele on obesity is still contradictory. Here, we aimed to elucidate the role of the 4G/5G polymorphism of the PAI-1 gene on the PAI-1 level and determine the associations between cytokines, glucose and lipid metabolism parameters in obese children. Thirty-nine obese children (mean age 11.4 +/- 3.3 years) and 38 age-matched healthy control group (mean age 10.3 +/- 3.5 years) were included in the study. In all cases, serum levels of glucose, lipid and insulin were measured, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, and 4G/5G polymorphism of PAI-1 gene, plasma PAI-1 level and serum TNFalpha and TGFbeta levels were studied. The mean relative body mass index (BMI) and HOMA-IR score, VLDL, TG, insulin, PAI-1, TNFalpha levels were higher, and HDL and TGFbeta levels were lower in the obese group. The frequency of the 4G/4G genotype was considerably higher in obese children than in controls. Also, a positive correlation was found between PAI-1 and TNFalpha levels, and relative BMI, HOMA-IR score, insulin, TG, HDL levels. TGFbeta was inversely correlated only with relative BMI. There was no correlation among three cytokines. In conclusion, childhood obesity contributes to higher PAI-1 and TNFalpha and lower TGFbeta levels. Especially PAI-1 and TNFalpha accompany insulin resistance and dyslipidemia.

The effects of metabolic control on oxidized low-density lipoprotein antibodies in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: To assess the oxidized low-density lipoprotein (oxLDL) antibody status in childhood type 1 diabetes mellitus (T1DM) and to investigate the effect of metabolic control on the oxLDL antibodies. SUBJECTS AND METHODS: The study included 36 T1DM patients (aged 6.6-18.1 yr) and 20 age- and sex-matched healthy subjects. Serum levels of oxLDL antibodies, lipids, and hemoglobin A1c (HbA1c) were measured. The patients with diabetes were divided into two groups according to their metabolic control levels. Group I (the patient group with good or fairly good metabolic control, n = 21) and group II (the patient group with poor metabolic control, n = 15) included children with diabetes having an actual HbA1c levels of < or = 9 and >9%, respectively. RESULTS: The oxLDL antibody level was higher in T1DM patients than in control subjects [278 (37-1289) vs. 110 (37-235) mU/mL] (p < 0.001). The patients with diabetes in group I had higher antibody levels against oxLDL [488 (51-1289) mU/mL] than both those in group II [183 (37-1207) mU/mL] and control group [110 (37-235) mU/mL] (p < 0.001). oxLDL antibodies were inversely correlated with actual HbA1c levels (r = -0.42, p = 0.01). CONCLUSIONS: Increased levels of oxLDL antibodies in pediatric patients indicate that the increased lipid peroxidation in T1DM begins in childhood. oxLDL antibody levels are inversely correlated with actual HbA1c levels in children with diabetes, as shown in adult patients. As metabolic control worsens, the free oxLDL antibody levels decrease perhaps because of immune complex formation and the atherosclerosis risk increases. The risk may be diminished by improving metabolic control as reflected in the correlation between current HbA1c and oxLDL levels.

Laryngitis and neutropenia from parvovirus-B19.

Parvovirus-B19 has been reported a rare cause of acute laryngitis. Here, we described an 11-month-old girl who had prolonged acute laryngitis and neutropenia associated with parvovirus-B19 infection. Intravenous immunoglobulin therapy resulted in resolution of her symptoms, except neutropenia. We concluded that parvovirus-B19 can cause prolonged laryngitis and intravenous immunoglobulin treatment should be considered.

The effect of obesity on echocardiographic and metabolic parameters in childhood.

BACKGROUND: Obese children are predisposed to left ventricular (LV) hypertrophy and cardiac dysfunction. We evaluated ventricular function of obese children with conventional echocardiography and tissue Doppler imaging (TDI) and correlated these with fasting serum glucose, lipid and insulin levels. METHODS: Thirty obese children were examined by conventional echocardiography and TDI and compared with an age-matched control group. In the obese children, fasting serum glucose, lipid, and insulin levels were obtained. RESULTS: Systolic and diastolic function of the LV was normal in obese children. LVM/ht2.7 (LVM normalized for height), relative wall thickness (RWT), and LV end-diastolic diameter were significantly greater in obese children. The early to late relaxation velocity ratio (E/A) determined by TDI for the right ventricle and interventricular septum (IVS) were significantly lower in the obese group, LVM/ht2.7 and RWT correlated with body mass index (BMI). In the obese group, IVS and LV posterior wall thickness correlated with insulin, very low density lipoprotein, and triglyceride levels. However, we failed to show this correlation when these measurements were indexed to height. CONCLUSION: Left ventricular hypertrophy, as evidenced by increased LV mass, was present in obese children. Higher BMI, insulin, very low density lipoprotein, and triglyceride levels were associated with LV hypertrophy. TDI revealed subclinical changes in diastolic function of the right ventricle and IVS.

Type 1 diabetes mellitus associated with nephrotic syndrome.

Nephrotic syndrome (NS) in a patient with diabetes mellitus (DM) first suggests the diagnosis of diabetic nephropathy. However, glomerular diseases other than diabetic nephropathy have been reported in patients with DM. We present a child with type 1 DM (DM1) associated with NS. A 3 year-old boy who was diagnosed with DM1 developed proteinuria in nephrotic range at the 10th month of follow-up. He had remission on steroid treatment without any problem in glycemic control as he was given tapered daily doses instead of an alternate day regimen. He relapsed at the 7th month of follow-up, and cyclophosphamide treatment brought about remission. He had HLA A24, DR4 and DR53 antigens in common with previously reported cases of DM-NS association. The immunological basis of these diseases may have a causal effect on the association, but the etiopathogenesis is still unclear.

Correlations among serum leptin levels, complete blood count parameters and peripheral CD34(+) cell count in prepubertal obese children.

Leptin is a hormone produced by adipocytes that helps reduce body weight by depressing appetite and increasing metabolic activity. Leptin also promotes early hematopoiesis. The main aim of this study was to compare complete blood count (CBC) parameters and peripheral blood CD34(+) cell counts in prepubertal obese and nonobese children. Relationships between leptin levels and CBC parameters and peripheral CD34(+) progenitor cell counts in the obese group were also investigated. Thirty one healthy, prepubertal, obese children and 30 nonobese, age-matched prepubertal controls were included in the study. A fasting blood sample was collected from each subject, and CBC findings, serum leptin level, and peripheral blood CD34(+) progenitor cell count were recorded. In the obese group, the mean results for body mass index (BMI), BMI standard deviation score (BMI SDS), and serum leptin level were significantly higher than the corresponding control findings. There were no significant differences between the groups with respect to CBC parameters and CD34(+) cell percentage. In both the obese and control groups, the girls' serum leptin levels were significantly higher than the boys'. In the obese group, serum leptin level was strongly correlated with BMI and with BMI SDS (Pearson correlation coefficients r=0.70, p<0.001, and r=0.59, p<0.001, respectively) in both girls and boys. None of the CBC parameters nor CD34(+) progenitor cell percentage was correlated with leptin, BMI, or BMI SDS. The results indicate that serum leptin levels in obese children are positively correlated with BMI. However, in contrast to adults, high leptin level in childhood obesity does not seem to be associated with altered CBC parameters or increased peripheral CD34(+) progenitor cell count.

Non-invasive management of fetal goiter during maternal treatment of hyperthyroidism in Grave's disease.

There is an increased risk of fetal goiter in patients who have a history of Grave's disease and undergo propylthiouracil (PTU) treatment during pregnancy. In this report, we describe a case of a fetal goiter detected by antenatal ultrasound at the 26th week of gestation in a mother treated with PTU for Grave's disease. A 32 x 38 x 20 mm fetal goiter was detected, each lobe measured 30 x 18 x 18 mm and estimated volume was 10 cm3. Subsequently, fetal thyroid function was assessed by umbilical fetal blood sampling. Cord blood showed elevated serum TSH (40.2 mU/l) and normal concentrations of free T4 (9.5 pmol/l) and free T3 (2.6 pmol/l). There were no other ultrasonographic signs of fetal hypothyroidism. Based on the above findings, the mother's PTU dosage was reduced to 50 mg daily from a total of 150 mg and weekly ultrasonographic examinations were performed. Six weeks after the initial ultrasound, a complete regression of the fetal goiter was noted. At the 34th week of gestation, the patient was delivered due to intrauterine growth restriction and oligohydramnios and gave birth to a male, weighing 1,920 g. The newborn thyroid was not palpable and thyroid ultrasonography was normal. Cord blood TSH was normal (8.4 mU/l) and free T4 was within lower normal limit (9.03 pmol/l). Ten days later, newborn thyroid function was normal and the baby did well afterwards. In conclusion, after the evaluation of fetal thyroid status, selected cases with fetal goiter can be initially managed without intrauterine treatment.

Autoimmune thyroiditis with associated proteinuria: report of two patients.

The association of renal disease and autoimmune thyroid disorders has been reported previously. Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels. We report here two adolescent girls with hyperthyroidism associated with transient proteinuria correlated with thyroid hormone levels. They had positive antithyroid peroxidase and antithyroglobulin antibodies. Ultrasonographic and scintigraphic findings of the thyroid gland were consistent with Graves' disease in both. Their renal functions were normal except proteinuria (daily protein excretion of 13.5 mg/m2/h in patient 1 and 11 mg/m2/h in patient 2). When they became euthyroid on antithyroid treatment, proteinuria decreased without associated hematuria and/or hypertension. In conclusion, patients with autoimmune thyroid disease should be assessed for the possibility of proteinuria and the etiological investigation of proteinuria should include evaluation of thyroid functions.