Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against β-cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout different temporal windows as single chemical agent or as chemical mixtures. They could affect the development and the function of the immune system or of the β-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D. We highlight what we know by animals about EDCs’ effects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions.

BackgroundChildren with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents.MethodsFifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3–18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters.ResultsHeight-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase.ConclusionsMetabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients.Electronic supplementary materialThe online version of this article (10.1186/s12887-019-1423-9) contains supplementary material, which is available to authorized users.

Sickle cell disease (SCD) is a life-threatening genetic disorder characterized by chronic hemolytic anemia, vascular injury and multiorgan dysfunctions. Over the last few decades, there have been significant improvements in SCD management in Western countries, especially in pediatric population. An early onset of prophylaxis with Penicillin and a proper treatment of the infections have increased the overall survival in childhood. Nevertheless, management of painful episodes and prevention of organ damage are still challenging and more efforts are needed to better understand the mechanisms behind the development of chronic organ damages. Hydroxyurea (Hydroxycarbamide, HU), the only medication approved as a disease-modifying agent by the United States Food and Drug Administration and the European Medicines Agency, is usually under-used, especially in developing countries. Currently, hematopoietic stem-cell transplantation is considered the only curative option, although its use is limited by lack of donors and transplant-related toxicity. SCD symptoms are similar in children and adults, but complications and systemic organ damages increase with age, leading to early mortality worldwide. Experts in comprehensive care of young patients with SCD, especially those approaching the transition age to adulthood, are missing, leading people to rely on urgent care, increasing health care utilization costs and inappropriate treatments. It would be important to establish programs of comprehensive healthcare for patients with SCD from birth to adulthood, to improve their quality and expectancy of life.

BackgroundChildren with Sickle Cell Disease (SCD) may show growth failure in comparison to healthy peers. Many factors as hematological status, endocrine and/or metabolic dysfunction, and nutritional status, may play an important role in growth failure. The aim of this study was to assess whether impaired growth and nutritional intake can affect SCD severity during childhood.MethodsWe conducted an observational study on children with SCD referring to our clinic for routine follow-up visits in a 6-month period. We collected information on weight, height and body mass index (BMI) and calculated their respective standardized scores (z). The nutritional intake was assessed through the last 24-h recall intake of total calories, macro- (proteins, lipids, carbohydrates) and micronutrients (calcium, iron, phosphorus, vitamins B1, PP, A, C, B2). Disease severity was assessed through total hemoglobin (Hb) and fetal hemoglobin (HbF), and lactic dehydrogenase (LDH) levels, and through the total number and days of hospitalizations, as well as the lifetime episodes of acute chest syndrome (ACS).ResultsTwenty nine children (14 males, 15 females) with SCD were enrolled; their mean age was 9.95 years (SD 3.50, min 3.72, max 17.18). Z-weight and z-BMI were significantly directly related to total Hb. Food intake resulted significantly unbalanced in terms of total calorie intake, macro- and micronutrients, especially calcium, iron, vitamin B1 and C. Low intake of calcium and vitamin B1 were significantly inversely correlated with number and days of hospitalizations per year. Protein, lipid, phosphorus, and vitamin PP intakes resulted adequate but were inversely correlated with number and days of hospitalizations. Carbohydrate, lipid, iron, phosphorus, vitamins B1 and B2 intakes were significantly inversely correlated to HbF levels.ConclusionsThis study showed that, in our population, inadequate nutritional intake, weight and BMI have a significant impact on SCD severity indices.

Background X-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1 . Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease. Case presentation A 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in the DAX-1 gene leading to the diagnosis of AHC. Conclusions AHC onset may involve the aldosterone production itself, miming an isolated defect of aldosterone synthesis. NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.