Context Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition, poorly characterized in children. Objective to describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI. Patients and methods data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected. Results the following etiologies were reported: 85% (n=682) Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n=25) X linked Adrenoleukodystrophy; 3.1% (n=25) Autoimmune Polyglandular syndrome type 1; 2.5% (n=20) autoimmune AI; 2% (n=16) Adrenal Hypoplasia Congenital; 1.2% (n=10) CAH non 21-OHD; 1% (n=8) rare syndromes; 0.6% (n=5) Familial Glucocorticoid Deficiency; 0.4% (n=3) acquired AI; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis different from 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%) and hypotension (31%). Elevated ACTH (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%) and hypoglycemia (33.7%). The median age at presentation was 6.5±5.1 years (0.1-17.8 years) and the mean length of symptoms before diagnosis was 5.6±11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patients years. Three patients died for the underlying disease. Adult height, evaluated in 70 patients, was -0.70±1.20 SDS. Conclusions we characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.

Hypoglycemia is the result of defects/impairment in glucose homeostasis. The main etiological causes are metabolic and/or endocrine and/or other congenital disorders. Despite hypoglycemia is one of the most common emergencies in neonatal age and childhood, no consensus on the definition and diagnostic work-up exists yet. Aims of this review are to present the current age-related definitions of hypoglycemia in neonatal-pediatric age, to offer a concise and practical overview of its main causes and management and to discuss the current diagnostic-therapeutic approaches. Since a systematic and prompt approach to diagnosis and therapy is essential to prevent hypoglycemic brain injury and long-term neurological complications in children, a comprehensive diagnostic flowchart is also proposed.

The epigenome bridges environmental factors and the genome, fine-tuning the process of gene transcription. Physiological programs, including the development, maturation and maintenance of cellular identity and function, are modulated by intricate epigenetic changes that encompass DNA methylation, chromatin remodeling, histone modifications and RNA processing. The collection of genome-wide DNA methylation data has recently shed new light into the potential contribution of epigenetics in pathophysiology, particularly in the field of immune system and host defense. The study of patients carrying mutations in genes encoding for molecules involved in the epigenetic machinery has allowed the identification and better characterization of environment-genome interactions via epigenetics as well as paving the way for the development of new potential therapeutic options. In this review, we summarize current knowledge of the role of epigenetic modifications in the immune system and outline their potential involvement in the pathogenesis of inborn errors of immunity.

<b><i>Introduction:</i></b> Growth hormone deficiency (GHD) may be associated with subtle cardiovascular abnormalities, reversible upon starting GH treatment. Data on vascular morphology and function in GHD children are scanty and inconclusive. The aim of our study was to evaluate the effects of GHD and GH treatment on endothelial function and intima-media thickness (IMT) in children and adolescents. <b><i>Methods:</i></b> We enrolled 24 children with GHD (10.85 ± 2.71 years) and 24 age-, sex-, and BMI-matched controls. We evaluated anthropometry, lipid profile, asymmetric dimethylarginine (ADMA), brachial flow-mediated dilatation (FMD), and IMT of common (cIMT) and internal (iIMT) carotid artery at study entry in all subjects and after 12 months of treatment in GHD children. <b><i>Results:</i></b> At baseline GHD, children had higher total cholesterol (163.17 ± 18.66 vs. 149.83 ± 20.68 mg/dL, <i>p</i> = 0.03), LDL cholesterol (91.18 ± 20.41 vs. 77.08 ± 19.73 mg/dL, <i>p</i> = 0.019), atherogenic index (AI) (2.94 ± 0.71 vs. 2.56 ± 0.4, <i>p</i> = 0.028), and ADMA (215.87 ± 109.15 vs. 164.10 ± 49.15 ng/mL, <i>p</i> &lt; 0.001), compared to controls. GHD patients also exhibited increased higher waist-to-height ratio (WHtR) compared to controls (0.48 ± 0.05 vs. 0.45 ± 0.02 cm, <i>p</i> = 0.03). GH therapy resulted in a decrease in WHtR (0.44 ± 0.03 cm, <i>p</i> = 0.001), total (151.60 ± 15.23 mg/dL, <i>p</i> = 0.001) and LDL cholesterol (69.94 ± 14.40 mg/dL, <i>p</i> &lt; 0.0001), AI (2.28 ± 0.35, <i>p</i> = 0.001), and ADMA (148.47 ± 102.43 ng/mL, <i>p</i> &lt; 0.0001). GHD showed lower baseline FMD than controls (8.75 ± 2.44 vs. 11.85 ± 5.98%, <i>p</i> = 0.001), which improved after 1-year GH treatment (10.60 ± 1.69%, <i>p</i> = 0.001). Baseline cIMT and iIMT were comparable between the two groups, but slightly reduced in GHD patients after treatment. <b><i>Conclusion:</i></b> GHD children may exhibit endothelial dysfunction in addition to other early atherosclerotic markers like visceral adiposity, and altered lipids, which can be restored by GH treatment.

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