Navegando por Palavras-chave "adrenal insufficiency"

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    Absolute and relative adrenal insufficiency in children with septic shock
    (Lippincott Williams & Wilkins, 2005-04-01) Pizarro, C. F.; Troster, E. J.; Damiani, D.; Carcillo, J. A.; Universidade Federal de São Paulo (UNIFESP)
    Objective: Corticosteroid replacement improves outcome in adults with relative adrenal insufficiency and catecholamine-resistant septic shock. We evaluated the relationship of absolute and relative adrenal insufficiency to catecholamine-resistant septic shock in children.Design. Prospective cohort study.Setting. University hospital pediatric intensive care unit in Brazil.Patients. Fifty-seven children with septic shock. Children with HIV infection, those with a history of adrenal insufficiency, and those submitted to any steroid therapy or etomidate within the week before diagnosis of septic shock were excluded.Interventions: None.Measurements and Main Results., A short corticotropin test (250 mu g) was performed, and cortisol levels were measured at baseline and 30 and 60 mins posttest. Adrenal insufficiency was defined by a response <= 9 mu g/dL. Absolute adrenal insufficiency was further defined by a baseline cortisol < 20 mu g/dL and relative adrenal insufficiency by a baseline cortisol > 20 mu g/dL. Absolute adrenal insufficiency was observed in 18% of children, all of whom had catecholamine-resistant shock. Relative adrenal insufficiency was observed in 26% of children, of whom 80% had catecholamine-resistant and 20% had dopamine/dobutamine-responsive shock. All children with fluid-responsive shock had a cortisol response > 9 mu g/dL. Children with adrenal insufficiency had an increased risk of catecholamine-resistant shock (relative risk, 1.88; 95% confidence interval, 1.26-2.79). However, mortality was independently predicted by chronic illness or multiple organ failure (p <.05), not adrenal insufficiency.Conclusions: Absolute and relative adrenal insufficiency is common in children with catecholamine-resistant shock and absent in children with fluid-responsive shock. Studies are warranted to determine whether corticosterold therapy has a survival benefit in children with relative adrenal insufficiency and catecholamine-resistant septic shock.
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    Caracterização clínica, molecular e imunológica de pacientes com síndrome poliglandular autoimune do tipo 1
    (Universidade Federal de São Paulo (UNIFESP), 2016-01-27) Weiler, Fernanda Guimarães [UNIFESP]; Castro, Marise Lazaretti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder defined by the association of at least two of the three major diseases: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and autoimmune adrenal insufficiency, however, many other autoimmune components may develop. In most cases, APS1 appears in infancy or childhood. The disease is caused by mutations in the AIRE gene, resulting in defective AIRE protein, which is essential for self-tolerance through thymic expression of peripheral self-proteins, and deletion of autoreactive T cells. In Brazil, however, the characteristics of APS1 patients are still unknown. Objective: To define the clinical profile of Brazilian APS1 patients; to perform mutational analysis of AIRE gene; to investigate genotype/phenotype correlations; to perform functional study of a novel mutation; and to measure specific autoantibodies. Patients and methods: Information about clinical history was evaluated by a questionnaire, and antibodies against interferon type I and interleukins 17A, 17F and 22 were measured in the sera of the patients. Genomic DNA was used to perform sequencing of all 14 exons and exon/intron boundaries of the AIRE gene. For localization analysis by immunofluorescence microscopy, HeLa cells were transfected with wild-type and mutant (c.560C>G) plasmids. Results: Thirteen patients with clinical diagnosis of APS1 were identified and in all cases the disease first appeared during infancy or childhood. Twenty different manifestations have been diagnosed. Besides being the first sign in the majority (77%), CMC was also the most frequent manifestation, present in all patients. Hypoparathyroidism was observed in 69% and adrenal insufficiency was diagnosed in 77%, while the complete triad was present in 54% of the sample. Every patient carried defects in AIRE, and among 10 identified mutations, 4 have never been reported (c.560C>G, c.966C>A, c.1096-2A>G and c.1347C>A). The most frequent mutation was the c.967_979del, which accounted for 36% of the alleles. As in other series, we were unable to identify correlations between phenotype and the detected mutations. Mutational analyses of relatives allowed the identification of APS1 in an asymptomatic child. In transiently transfected cells, the mutant c.560C>G protein was observed as abnormal perinuclear aggregates, which suggested the mutation harmful potential. All 10 confirmed APS1 patients that were tested for anti-interferon type I showed positive results, and we have found that anti-interleukin-17A titers were negatively correlated with number of manifestations in each patient. Thirteen patients suspected of having the syndrome were also investigated; one of them displayed another new mutation of AIRE, which is expected to be deleterious according to in silico simulations. Conclusions: We were able to identify 14 Brazilian patients with APS1, one of them still asymptomatic. In our cohort, CMC was the most prevalent disease, while the most common mutation was c.967_979del. We detected 4 novel mutations, and another mutation likely to be deleterious in a patient suspected of having the syndrome was also reported. Titers of anti-interleukin-17A were negatively correlated with number of manifestations. Screening for AIRE mutations and analysis of specific auto-antibodies are useful tools to establish the diagnosis in initial or atypical situations.