Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables

BackgroundTo investigate possible differences in emotional/behavioral problems and cognitive function in children with nephrotic syndrome compared to healthy controls and to examine the effect of disease-specific and steroid treatment-specific characteristics on the abovementioned variables. MethodsForty-one patients with nephrotic syndrome (23 boys, age range: 4.4-15.2 years) and 42 sex- and age-matched healthy control subjects (20 boys, age range: 4.1-13.4 years) were enrolled in the study. Disease (severity, age of diagnosis, duration) and steroid treatment (total duration, present methylprednisolone dose and duration of present dose) data were collected. In order to assess children’s emotional/behavioral problems, the Child Behavior Checklist was administered. The Wechsler Intelligence Scale for Children – Third Edition was administered to assess Full-Scale, Verbal, and Performance intelligence quotient (IQ) scores. ResultsThe patients presented with more internalizing problems (P = 0.015), including withdrawal (P = 0.012) and somatic complaints (P = 0 .011), but not more anxiety/depression or externalizing problems. A significant association was found between severity of disease and somatic complaints (P = 0.017) as well as externalizing problems (P = 0.030). Years of illness were significantly more in those presenting with abnormal anxiety/depression (P = 0.011). Duration of steroid medication was significantly higher among those presenting with abnormal anxiety/depression (P = 0.011) and externalizing problems (P = 0.039). IQ was not associated significantly with disease or steroid treatment variables. ConclusionsPsychosocial factors and outcomes may be important correlates of children’s nephrotic syndrome and potential targets of thorough assessment and treatment

Infection rate by cytomegalovirus, yersinia enterocolitica and toxoplasma gondii in patients with β-thalassemia

In this study we detected the infection rate by Cytomegalovirus, Toxoplasma Gondii and Yersinia Enterocolitica in patients with β-thalassemia and their household contacts. We studied a total of 503 individuals that is 123 β-thalassemic patients, 146 of their household contacts and 234 healthy control subjects of the same age. Antibodies to CMV (cytomegalovirus) and Toxoplasma were detected using enzyme immunoassays (EIAS), whereas for the detection of antibodies to Yersinia we used the indirect hemaglutination technique. Our findings demonstrated that: 81,3% of the thalassemic patients were seropositive to CMV, whereas the seropositivity rate in the control subjects was 59,3% (p0,5). Επίσης οι οικείοι των ασθενών και οι αντίστοιχοι μάρτυρες έδειξαν την ίδια συχνότητα οροθετικότητας (0,7%) έναντι της Yersinia Enterocolitica

Hypertension in Cushing's syndrome

Cushing’s syndrome can be exogenous, resulting from the administration of glucocorticoids or adrenocorticotrophic hormone (ACTH), or endogenous, secondary to increased secretion of cortisol or ACTH. Hypertension is one of the most distinguishing features of endogenous Cushing’s syndrome, as it is present in about 80% of adult patients and in almost half of children and adolescents patients. Hypertension results from the interplay of several pathophysiological mechanisms regulating plasma volume, peripheral vascular resistance and cardiac output, all of which may be increased. The therapeutic goal is to find and remove the cause of excess glucocorticoids, which, in most cases of endogenous Cushing’s syndrome, is achieved surgically. Treatment of Cushing’s syndrome usually results in resolution or amelioration of hypertension. However, some patients may not achieve normotension or may require a prolonged period of time for the correction of hypercortisolism. Therefore, therapeutic strategies for Cushing’s-specific hypertension (to normalise blood pressure and decrease the duration of hypertension) are necessary to decrease the morbidity and mortality associated with this disorder. The various pathogenetic mechanisms that have been proposed for the development of glucocorticoid-induced hypertension in Cushing’s syndrome and its management are discussed

Long-term clinical data and molecular defects in the STAR gene in five Greek patients

Context: Steroidogenic acute regulatory (STAR) gene mutations lead to adrenal and gonadal failure. Interesting, though as yet unexplained, features are the formation of ovarian cysts and the potential presence of CNS findings. Objective: To report biochemical, genetic, and long-term clinical data in five Greek patients from four different families with STAR gene defects (three 46, XX and two 46, XY). Methods and results: All patients presented in early infancy with adrenal insufficiency. The STAR gene mutation c.834del11bp, detected in three of our patients, completely alters the carboxyl end of the STAR protein and has not thus far been described in other population groups. These three patients belong to three separate families, possibly genetically related, as they live in different villages located in a small region of a Greek island. However, their interrelationship has not been proven. A second mutation, p.W250X, detected in our fourth family, was previously described only in two Serbian patients. Ovarian cysts were detected ultrasonographically in our 46, XX patients and seemed to respond to a low dose of a contraceptive. The histology of an excised ovarian cyst was diagnosed as a corpus luteum (CL) cyst. In two out of the four patients who had undergone brain magnetic resonance imaging, asymptomatic Chiari-1 malformation was observed. Conclusions: The occurrence of STAR gene mutation c.834del11bp in three families living in a restricted geographic region could indicate either a founder effect or simply reflect a spread of this defect in a highly related population. The ovarian histological findings suggest that ovarian cysts detected ultrasonographically in 46, XX individuals with STAR gene defects may be CL cysts. The Chiari-1 malformation in two of our patients may be part of the STAR gene mutation phenotype. Nevertheless, more data are needed to confirm or disprove the existence of specific CNS pathology in patients with STAR gene mutations. European Journal of Endocrinology 168 351-35

Pituitary Stalk Interruption Syndrome and Isolated Pituitary Hypoplasia May Be Caused by Mutations in Holoprosencephaly-Related Genes

Context: Holoprosencephaly (HPE) is a developmental defect characterized by wide phenotypic variability, ranging from minor midline malformations (eg, single central incisor) to severe deformities. In 10-15% of HPE patients, mutations in specific genes have been identified (eg, SHH, TGIF, SIX3). Pituitary stalk interruption syndrome (PSIS) constitutes a distinct abnormality of unknown pathogenesis, whereas isolated pituitary hypoplasia (IPH) has been linked to various developmental genes. Objective: Three of our patients with PSIS had a single central incisor, a malformation encountered in some HPE cases. Based on this observation, we initiated a search for mutations in HPE-associated genes in 30 patients with PSIS or IPH. Design and Participants: The entire coding region of the TGIF, SHH, and SIX3 genes was sequenced in patients with combined pituitary hormone deficiency associated with either PSIS or IPH and in healthy controls. Results: Two novel mutations in the HPE-related genes were detected (ie, c.799 C>T, p.Q267X in the TGIF gene, and c.1279G>A, p.G427R in the SHH gene) in 2 of our patients. The overall incidence of HPE-related gene mutations in our nonsyndromic and nonchromosomal patients was 6.6%. No molecular defect in the SIX3 gene was detected in our cohort. Conclusions: The data suggest that HPE-related gene mutations are implicated in the etiology of isolated pituitary defects (PSIS or IPH). Alternatively, PSIS or IPH may constitute mild forms of an expanded HPE spectrum. (J Clin Endocrinol Metab 98: E779-E784, 2013

Screening for Congenital Hypothyroidism: The Significance of Threshold Limit in False-Negative Results

Context: In our neonatal program, a number of infants with congenital hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of 20 mU/liter whole blood was used as a cutoff point. Objective: The objective of the study was to find out prospectively the additional number of newborns with CH if the TSH cutoff point is lowered to 10 mU/liter. Population and Methods: The study included 311,390 screened newborns. The children with CH were followed up for a period of 3 yr. Results: Twenty-eight percent of infants diagnosed with CH had neonatal TSH values between 10 and 20 mU/liter (56 of 200). Forty of 47 infants, who were reevaluated later on (85.1%), suffered permanent CH. A thyroid scintiscan and/or echogram revealed that eight of 40 children (20.0%) had a structural defect, and the remaining (32 of 40) had a functional defect of the thyroid gland without anatomical abnormality; 14 of 32 cases were familial. Eighteen of the 47 reevaluated infants were prematurely born (38.3%) and 15 of these 18 had permanent CH (83.3%). The lowering of TSH cutoff point from 20 to 10 mU/liter resulted in a 10-fold increase of recall rate. Conclusions: A significant number of cases with permanent CH are missed when a TSH threshold of 20 mU/liter is applied. Almost 40% of the missed CH cases were premature. A mild increase of TSH at screening is not a predictor of transient CH. The increase in recall rate constitutes a serious drawback and should be balanced against the possible consequences of thyroid dysfunction at this important developmental stage. (J Clin Endocrinol Metab 95: 4283-4290, 2010

Glucose dysregulation in obese children: Predictive, risk, and potential protective factors

Objective: The aim of our study was to determine the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (DM2) in obese children and adolescents of Greek origin and compare our data with pertinent literature findings in an attempt to uncover predictive, risk, and preventive factors. Research Methods and Procedures: A total of 117 obese children and adolescents 12.1 +/- 2.7 years old underwent a 2-hour oral glucose tolerance test (OGTT). Insulin resistance (IR) and beta-cell function were estimated using the homeostasis model assessment (HOMA)-IR and the insulinogenic index, respectively. Results: A total of 17 patients (14.5%) had IGT, and none had DM2. The overall prevalence rates of both IGT and DM2 in our subjects were lower than those reported in a recent multiethnic U.S. study. Nevertheless, the difference between our IGT data and those of the U.S. study was due mostly to the prepubertal subjects (9% vs. 25.4%), whereas no difference was observed in the pubertal population (18% vs. 21%). Fasting glucose, insulin, and HOMA-IR values were not predictive of IGT. The absolute value of insulin at 2 hours of the OGTT combined with the time-integrated glycemia (AUCG) can strongly predict IGT, whereas higher area under the curve for insulin (AUCI) values were found to be protective. Discussion: In ethnic groups less prone to diabetes development, IGT or DM2 in obese subjects is more likely to develop at puberty than at the prepubertal stage. It is advisable that physicians caring for obese adolescents perform an OGTT for early detection of IGT because HOMA-IR values, although higher in IGT subjects and indicative of IR, cannot predict IGT

Elevated coagulation and inflammatory markers in adolescents with a history of premature adrenarche

Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P =.0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P =.0001) and plasminogen activator inhibitor I (r = 0.36, P =.04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P.02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in Subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved