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The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often nec

A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms (fatigue, anorexia, weight loss, hypotension, hyponatremia and hyperkalemia amongst adrenal causes of insufficiency). The diagnosis should be considered in case of pituitary disease or a state of shock. Treatment should be commenced immediately without waiting for confirmation from biochemical tests, which rely on cortisol level at 8am (expected to be low) and on ACTH level (expected to be high in the case of primary adrenal insufficiency). If these tests are inconclusive, a Synacthen test should be carried out. The threshold limits are provided as a guide. Low plasma cortisol and normal to low plasma ACTH indicates a pituitary origin for the deficiency. In this situation, the Synacthen test can give a false normal result, and if this adrenal insufficiency is strongly suspected, an insulin hypoglycemia test or metyrapone (Metopirone) test should be carried out. In children younger than 2yr, hypoglycemia, dehydration and convulsions are frequently observed and in young girls, virilization is suspect of congenital adrenal hyperplasia . The circadian rhythm of cortisol is not present until after 4months of age and the Synacthen test is the only one that is feasible. In children older than 2yrs, the signs and diagnostic methods are the same as in the adult. Cessation of corticosteroid treatment is a frequent circumstance however there is little published data and no evidence for definitive guidelines. After ceasing a short period of corticosteroid treatment, patient education is all that is required. After longer treatment, consensus leaves the choice up to the physician, between educating the patient and prescribing hydrocortisone in case of stress, or prescribing low daily dose hydrocortisone and evaluating the ACTH axis over time until normal function is recovered., [Groupe 2 : insuffisance surrénale : méthodes de dépistage et confirmation du diagnostic] Le diagnostic d’insuffisance surrénale doit être évoqué devant des symptômes non spécifiques (fatigue, anorexie, amaigrissement, hypotension, hyponatrémie, hyperkaliémie dans les causes surrénaliennes…). Il faut la rechercher devant une maladie hypophysaire. Il faut y penser aussi devant un état de choc. Le traitement doit être débuté sans attendre la confirmation biologique qui repose sur le dosage du cortisol à 8 heures (que l’on attend abaissé) et de l’ACTH (que l’on attend élevée dans les causes surrénaliennes). Ces dosages sont complétés dans les situations limites par un test au Synacthène. Des seuils sont donnés à titre indicatif. Devant un cortisol abaissé, l’ACTH normale ou basse indique l’origine hypophysaire du déficit. Dans cette situation, le test au Synacthène peut être faussement normal et si la suspicion est forte, il faut réaliser une hypoglycémie insulinique ou un test à la Metopirone®. Chez le jeune enfant, l’hypoglycémie, la déshydratation, les convulsions sont fréquentes, une virilisation est évocatrice chez la fille d'hyperplasie surrénale congénitale. Le rythme circadien du cortisol ne prend place qu’après l’âge de 4 mois. Le test au Synacthène est donc le seul réalisable à cet âge. Chez l’enfant après 2 ans, les signes d’appel et les méthodes diagnostiques sont les mêmes que chez l’adulte. Le sevrage d’une corticothérapie est une circonstance fréquente pour laquelle les données de la littérature manquent. Apres arrêt d’une corticothérapie courte, seule l’éducation du patient est nécessaire. Pour les traitements longs, le consensus laisse le choix au prescripteur entre éducation du patient et prescription d’hydrocortisone en cas de stress ou prescription d’une petite dose d’hydrocortisone quotidienne et évaluation itérative de l’axe corticotrope jusqu’à récupération de l’axe.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period., Funding Agencies|Diamyd Medical||Swedish Child Diabetes Foundation (Barndiabetesfonden)

Context: In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential. Objective: The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis. Setting: The study was performed at Montpellier University Hospital. Patients: We studied a cohort of 55 patients with srd5A2 gene mutations. Main Outcome Measure(s): Genetic analysis of srd5A2 was conducted. Results: Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively. Conclusions: In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins. Copyright © 2011 by The Endocrine Society., SCOPUS: ar.j, info:eu-repo/semantics/published