Groupe 4 : traitement substitutif de l’insuffisance surrénale

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Health-related quality of life of patients with hypothalamic–pituitary–adrenal axis dysregulations: a cohort study

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Triple-A syndrome: a wide spectrum of adrenal dysfunction

International audienceObjective: Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is characterized by a classical clinical triad: alacrima, achalasia and adrenal insufficiency, the canonic symptoms that are associated with progressive peripheral neuropathy. Only a few cohorts have been reported. The objective of the present study was to characterize the various spectra of adrenal function in Triple-A patients. Methods: A retrospective clinical and biological monitoring of 14 patients (10 families) was done in a single multidisciplinary French center. All had AAAS gene sequenced and adrenal function evaluation. Results: Nine different AAAS mutations were found, including one new mutation: c.755G\textgreaterC, p.(Trp252Ser). Regarding adrenal function, defects of the zona fasciculata and reticularis were demonstrated by increased basal ACTH levels and low DHEAS levels in all cases regardless of the degree of glucocorticoid deficiency. In contrast, mineralocorticoid function was always conserved: i.e., normal plasma renin level associated with normal aldosterone level. The main prognostic feature was exacerbation of neuropathy and cognitive disorders. Conclusions: These data suggest that, in Triple-A patients, adrenal function can be deficient, insufficient or compensated. In our cohort after the first decade of life, there does not appear to be any degradation of adrenal function over time. However, patients with compensated adrenal function should be informed and educated to manage a glucocorticoid replacement therapy in case of stressful conditions, with no need for systematic long-term treatment

Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis.

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

Activating PRKACB somatic mutation in cortisol-producing adenomas

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Activating PRKACB somatic mutation in cortisol-producing adenomas

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