Alice Monzani

ENDOCRINE DISORDERS IN CHILDHOOD AND ADOLESCENCE: Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review

OBJECTIVEnSubclinical hypothyroidism (SH) is quite common in children and adolescents. The natural history of this condition and the potential effects of replacement therapy need to be known to properly manage SH. The aim of this review is to analyze: i) the spontaneous evolution of SH, in terms of the rate of reversion to euthyroidism, the persistence of SH, or the progression to over hypothyroidism; and ii) the effects of replacement therapy, with respect to auxological data, thyroid volume, and neuropsychological functions.nnnMETHODSnWe systematically searched PubMed, Cochrane, and EMBASE (1990-2012) and identified 39 potentially relevant articles of which only 15 articles were suitable to be included.nnnRESULTS AND CONCLUSIONSnSH in children is a remitting process with a low risk of evolution toward overt hypothyroidism. Most of the subjects reverted to euthyroidism or remained SH, with a rate of evolution toward overt hypothyroidism ranging between 0 and 28.8%, being 50% in only one study (nine articles). The initial presence of goiter and elevated thyroglobulin antibodies, the presence of celiac disease, and a progressive increase in thyroperoxidase antibodies and TSH value predict a progression toward overt hypothyroidism. Replacement therapy is not justified in children with SH but with TSH 5-10u200amIU/l, no goiter, and negative antithyroid antibodies. An increased growth velocity was observed in children treated with levothyroxine (l-T(4); two articles). l-T(4) reduced thyroid volume in 25-100% of children with SH and autoimmune thyroiditis (two studies). No effects on neuropsychological functions (one study) and posttreatment evolution of SH (one study) were reported.

Use of Deamidated Gliadin Peptide Antibodies to Monitor Diet Compliance in Childhood Celiac Disease

Objective: The aim of this study was to evaluate performance of serum antibodies against deamidated gliadin peptides (a-DGPs) in detecting compliance with gluten-free diet (GFD) in children with celiac disease (CD). Patients and Methods: Serum samples were collected the same day of endoscopy in 95 children with CD and 106 controls. We preliminarily calculated the cutoff of a-DGP immunoglobulin A (IgA) and a-DGP IgA+G in our population by receiver operating characteristic (ROC) curves. Of 95 children with CD, 28 were studied during the first year after GFD introduction, with interview and serum collection every 3 months. In addition, serum samples were collected in 106 children with CD on GFD for more than 1 year (range 1–14). In both groups of children with CD on GFD, we compared a-DGP IgA and IgA+G performance in monitoring compliance with GFD with anti-tissue transglutaminase antibodies (anti-tTG) IgA and anti-gliadin antibody (AGA) IgA. Results: The cutoff resulted in 13.1 arbitrary units (AU) for a-DGP IgA (sensitivity 87.4, 95% confidence interval [CI] 79%–92%, specificity 97.2, 95% CI 92%–99%) and 16.5 for a-DGP IgA+G (sensitivity 94.7, 95% CI 88%–98%, specificity 89.6, 95% CI 84%–95%). In the first year of GFD, at 6 to 8 months prevalence of positive a-DGPs was significantly higher in partially versus strictly compliant children, and at 9 to 12 months only prevalence of positive a-DGP IgA+G remained significantly higher. Moreover, at 9 to 12 months sensitivity to detect transgressions to GFD was 44% for a-DGP IgA and 100% for a-DGP IgA+G (P = 0.03). In the 106 children on GFD for more than 1 year, sensitivity to detect transgressions to GFD was 60% for a-DGP IgA and 76% for a-DGP IgA+G. Anti-tTG IgA and AGA IgA sensitivity was much lower (24% and 4%, respectively). The 4 tests showed comparable high specificity. Conclusions: Both a-DGPs showed higher sensitivity than anti-tTG IgA and AGA IgA in monitoring compliance with GFD, but a-DGP IgA+G seemed to perform better. a-DGPs did not outperform anti-tTG IgA for CD screening.

Systematic Review of Ghrelin Response to Food Intake in Pediatric Age, From Neonates to Adolescents

OBJECTIVEnFood intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelins changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence.nnnMETHODSnWe searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included.nnnRESULTS AND CONCLUSIONSnTotal ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.

Metabolic syndrome is strictly associated with parental obesity beginning from childhood.

We aimed to identify potential correlates or risk factors for metabolic syndrome (MetS) in a cohort of schoolchildren. We quantified the prevalence of MetS, analysed the clustering of MetS components and described the distribution of metabolic parameters not included in MetS definition.

Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review.

Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009) and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%). Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7%) in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%). In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily) for at least 12 weeks is highly effective in childhood esophagitis.

High Discrepancy in Abdominal Obesity Prevalence According to Different Waist Circumference Cut-Offs and Measurement Methods in Children: Need for Age-Risk-Weighted Standardized Cut-Offs?

Background Waist circumference (WC) is a good proxy measure of central adiposity. Due to the multiplicity of existing WC cut-offs and different measurement methods, the decision to use one rather than another WC chart may lead to different prevalence estimates of abdominal obesity in the same population. Aim of our study was to assess how much the prevalence of abdominal obesity varies in Italian schoolchildren using the different available WC cut-offs. Methods We measured WC at just above the uppermost lateral border of the right ilium in 1062 Italian schoolchildren aged 7–14 years, 499 living in Northern Italy and 563 in Southern Italy. Abdominal obesity was defined as WC ≥90th percentile for gender and age according to nine WC charts. Results We found an extremely high variability in the prevalence of abdominal obesity detected in our study-populations according to the different WC charts, ranging in the overall group from 9.1% to 61.4%. In Northern Italy children it varied from 2.4% to 35.7%, and in Southern ones from 15.1% to 84.2%. Conclusions On the basis of the chosen WC cut-offs the prevalence of abdominal obesity varies widely, because percentile-charts are strongly influenced by the population status in a particular moment. A further rate of variability may lay on the site of WC measurement and on the statistical method used to calculate WC cut-offs. Risk-weighted WC cut-offs measured in a standardized anatomic site and calculated by the appropriate method are needed to simply identify by WC measurement those children at high risk of cardio-metabolic complications to whom specific and prompt health interventions should be addressed.

Etiology of Congenital Hypothyroidism

Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. According to the duration of thyroid hormone deficiency, it may be classified into permanent and transient CH. According to the anatomic location of the pathogenic defect, CH may be further classified into primary, secondary (or central), and peripheral CH. The most frequent cause of permanent primary CH is thyroid dysgenesis, which includes thyroid ectopy, agenesis, and hypoplasia. Thyroid dysgenesis is generally sporadic in occurrence, but in about 2 % of cases, mutations in genes PAX8, TTF-2, NKX2.1, and NXK2.5 may be detected. Dyshormonogenesis is the second most common cause and may be caused by mutations in genes encoding the sodium-iodide symporter, thyroperoxidase, hydrogen peroxide generation factors, thyroglobulin, iodothyronine deiodinase, and pendrin. Rare causes of CH include resistance to TSH binding or signaling, central CH, and peripheral CH caused by thyroid hormone syndrome or defects in thyroid hormone transport and metabolism.

A female newborn with papulovesicular lesions

A female newborn of Pakistani origin presented at birth with papulovesicular lesions with a surrounding erythematous base on the trunk and all four limbs. The baby was born at term after an uneventful pregnancy and vaginal delivery. She had a weight of 3,400 grams and an APGAR score of 9 at the 1 st and 5 th minute. Her parents were not blood-related. The mother was 26 years of age, healthy and without a history of abortion; her three-year-old fi rstborn female was in good health. A female newborn with papulovesicular lesions Case for Diagnosis

Hormones and Gastrointestinal Function

Development is a continuous process. Nutrition, environment and stress modulate development through gene expression in an epigenetic manner. Prenatal and perinatal nutrition can be imprinting factors and turn on different genes that provide different phenotypes, such as the thrifty phenotype [1]. Indeed, the nutritional support of gastrointestinal growth and function is an important tool in the clinical care of newborn babies, in particular preterm neonates. Before birth, although amniotic fluid is not the main source of nutrition for the fetus, it contributes up to 15% of fetal nutritional requirements and plays a key role in its development and maturation [2, 3]. Accordingly, by 20 weeks of gestation, the anatomy of the fetal gut resembles that of the term neonate. However, the process of intestinal absorption is only partially mature before 26 weeks of gestation: gastro-entero-pancreatic peptides are secreted at a basal rate and can be completely stimulated or inhibited after delivery, in particular through contact with nutrients [4, 5]. At the age of 2 years, the intestine is fully functional [6]. Gut hormones, peptides, and growth factors clearly have a role in gut growth after birth and directly and indirectly mediate the trophic actions of enteral nutrition in a manner that is still incompletely understood [5]. By contrast, hormones and growth factors, which are present in breast milk, also seem to exert trophic activities on gut development and immune function. The interplay is complex [1, 3]. Little is known about the development of these regulatory systems in the human neonate and, as a consequence, premature infants experience significant morbidity and mortality associated with feeding problems [6]. Present clinical nutritional support for preterm babies consists of enteral and parenteral nutrition but both have associated complications [6, 7]. Since enteral feeding is important for gut development, acute or chronic gastrointestinal diseases could be caused by feeding with formula rather than human breast milk. Formula milks contain higher amounts of proteins and lack many endogenous hormones and growth factors [5, 6, 8]. A better understanding of factors linked to gastrointestinal function and energy metabolism could result in improved strategies for supporting nutrition of preterm newborns as well as their later development.