Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that? / Uso de corticosteroides orais nas exacerbações da asma pode estar associado à supressão adrenal: os médicos estão alertas?

Summary Introduction: Oral corticosteroids (OCS) are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS) trial. Method: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006). Results: In all, 140 children (0.3-15 years old) with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29) nor in the last OCS course duration (p=0.20). The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89). Conclusion: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing.

Resumo Introdução: A corticoterapia oral (CO) é um dos pilares do tratamento na exacerbação da asma, e cursos de curta duração são geralmente considerados seguros. No entanto, crianças submetidas a repetidos cursos estão sujeitas a disfunção do eixo hipotálamo-hipófise-adrenal (HHA). Objetivo: Investigar a integridade do eixo HHA em crianças com asma persistente ou sibilância recorrente com indicação para corticoterapia inalatória (CI). Método: Avaliação do cortisol sérico basal antes da introdução da CI e 30, 60 e 90 dias após iniciado o tratamento, utilizando-se o imunoensaio ImmuliteÒ Siemens Medical Solutions Diagnostic chemiluminescent (Los Angeles, EUA; 2006). Resultados: Das 140 crianças avaliadas (0,3 a 15 anos de idade) com asma persistente ou sibilância recorrente, 40% relataram ter recebido CO no último mês antes da avaliação. Cerca de 12,5% delas apresentaram supressão adrenal bioquímica e evoluíram com recuperação do eixo HHA durante os primeiros três meses em CI. O número de dias livres de CO e a duração do último curso antes da avaliação do cortisol não foram significativamente diferentes entre as crianças com ou sem supressão adrenal (p=0,29 e p=0,20, respectivamente). O número de cursos de curta duração relatados no ano anterior à avaliação também não esteve associado à supressão adrenal (p=0,89). Conclusão: A utilização dos corticosteroides nas doses convencionais, em cursos de curta duração, pode colocar as crianças em risco de disfunção do eixo HHA. A recuperação desse eixo é possível durante a CI. Profissionais de saúde devem estar atentos para a possibilidade de resposta inadequada ao estresse durante o acompanhamento de crianças com asma persistente ou sibilância recorrente.

Para entender la acción de cortisol en inflamación aguda: una mirada desde la glándula suprarrenal hasta la célula blanco / Understanding cortisol action in acute inflammation: a view from the adrenal gland to the target cell

Glucocorticoids (cortisol in humans) are essential for numerous biological functions. Among critically ill patients, therapy with cortisol has gained strength in recent years, but clinical results have been mixed. A series of events, that may explain the diversity of clinical responses, occur from the synthesis of cortisol in the adrenal gland to the activation of the cortisol receptor by the hormone when it enters the nucleus of the target cell. Some of these events are revised; a proposition for identifying critically ill patients who may benefit with this therapy is suggested.

Conduct protocol in emergency: Acute adrenal insufficiency / Protocolo de condutas em emergência: insuficiência adrenal aguda

Summary Introduction: Acute adrenal insufficiency or addisonian crisis is a rare comorbidity in emergency; however, if not properly diagnosed and treated, it may progress unfavorably. Objective: To alert all health professionals about the diagnosis and correct treatment of this complication. Method: We performed an extensive search of the medical literature using specific search tools, retrieving 20 articles on the topic. Results: Addisonian crisis is a difficult diagnosis due to the unspecificity of its signs and symptoms. Nevertheless, it can be suspected in patients who enter the emergency room with complaints of abdominal pain, hypotension unresponsive to volume or vasopressor agents, clouding, and torpor. This situation may be associated with symptoms suggestive of chronic adrenal insufficiency such as hyperpigmentation, salt craving, and association with autoimmune diseases such as vitiligo and Hashimoto's thyroiditis. Hemodynamically stable patients may undergo more accurate diagnostic methods to confirm or rule out addisonian crisis. Delay to perform diagnostic tests should be avoided, in any circumstances, and unstable patients should be immediately medicated with intravenous glucocorticoid, even before confirmatory tests. Conclusion: Acute adrenal insufficiency is a severe disease that is difficult to diagnose. It should be part of the differential diagnosis in cases of hypotensive patient who is unresponsive to vasoactive agents. Therefore, whenever this complication is considered, health professionals should aim specifically at this pathology.

Resumo Introdução: a insuficiência adrenal aguda ou crise addisoniana é uma comorbidade rara na emergência; porém, se não diagnosticada e tratada de forma correta, pode evoluir de maneira desfavorável. Objetivo: alertar a todos os profissionais da saúde sobre o diagnóstico e tratamento corretos dessa complicação. Método: foi realizada uma ampla pesquisa na literatura médica, por meio de ferramentas específicas, sendo selecionados 20 artigos sobre o tema. Resultados: a crise addisoniana é de difícil diagnóstico pela inespecificidade de seus sinais e sintomas. No entanto, pode ser suspeitada em pacientes que chegam à emergência com queixa de dor abdominal, hipotensão não responsiva a volume ou a agentes vasopressores, obnubilação e torpor. Esse quadro pode vir associado a sintomas sugestivos de insuficiência adrenal crônica, como hiperpigmentação e avidez por sal, bem como a doenças autoimunes, como vitiligo e tireoidite de Hashimoto. Pacientes estáveis hemodinamicamente podem passar por métodos diagnósticos mais apurados para se confirmar ou descartar a crise addisoniana. Os exames diagnósticos não podem retardar, em hipótese alguma, o tratamento de pacientes instáveis, que deve ser iniciado imediatamente com glicocorticoide endovenoso, inclusive antes das provas confirmatórias. Conclusão: a insuficiência adrenal aguda é uma patologia grave e de difícil diagnóstico, que deve fazer parte do diagnóstico diferencial do médico ao atender um paciente hipotenso sem reposta à infusão de drogas vasoativas. Logo, na suspeita dessa complicação, o profissional não deve tardar a agir especificamente nessa patologia.

Neonatal cholestasis in congenital pituitary hormone deficiency and isolated hypocortisolism: characterization of liver dysfunction and follow-up / Colestase neonatal na deficiência congênita de hormônio hipofisário e hipocortisolismo isolado: caracterização da disfunção hepática e acompanhamento

INTRODUCTION: Neonatal cholestasis due to endocrine diseases is infrequent and poorly reco-gnized. Referral to the pediatric endocrinologist is delayed. OBJECTIVE: We characterized cholestasis in infants with congenital pituitary hormone deficiencies (CPHD), and its resolution after hormone replacement therapy (HRT). SUBJECTS AND METHODS: Sixteen patients (12 males) were included; eleven with CPHD, and five with isolated central hypocortisolism. RESULTS: Onset of cholestasis occurred at a median age of 18 days of life (range 2-120). Ten and nine patients had elevated transaminases and γGT, respectively. Referral to the endocrinologist occurred at 32 days (range 1 - 72). Remission of cholestasis occurred at a median age of 65 days, whereas liver enzymes occurred at 90 days. In our cohort isolated, hypocortisolism was a transient disorder. CONCLUSION: Cholestasis due to hormonal deficiencies completely resolved upon introduction of HRT. Isolated hypocortisolism may be a transient cause of cholestasis that needs to be re-evaluated after remission of cholestasis.

INTRODUÇÃO: A colestase neonatal causada por doenças endócrinas é pouco frequente e reconhecida. Existe um atraso no encaminhamento dos pacientes a um endocrinologista pediátrico. OBJETIVO: Caracterizamos a colestase em recém-nascidos com deficiências congênitas de hormônio hipofisário (DCHH) e sua resolução após a terapia de reposição hormonal (TRH). SUJEITOS E MÉTODOS: Dezesseis pacientes (12 do sexo masculino) foram incluídos; sete com DCHH, e cinco com hipocortisolismo central isolado. RESULTADOS: O início da colestase ocorreu aos 18 dias de vida (variação 2-120). Dez e nove pacientes apresentaram elevação das transaminases e γGT, respectivamente. A consulta com um endocrinologista aconteceu aos 32 dias (variação 1-72). A remissão da colestase ocorreu em uma idade mediana de 65 dias, enquanto a remissão das enzimas hepáticas aconteceu aos 90 dias. Na coorte isolada, o hipocortisolismo foi uma desordem transitória. CONCLUSÃO: A colestase causada por deficiências hormonais foi completamente resolvida após a introdução da TRH. O hipocortisolismo pode ser uma causa transitória da colestase e precisa ser reavaliado após a remissão da colestase.

Disfunción suprarrenal en el paciente cirrótico, ¿síndrome hepatoadrenal o síndrome del “euadrenálico” enfermo? / Adrenal dysfunction in the cirrhotic patient, ¿hepatoadrenal syndrome or the non adrenal illness syndrome?

Adrenal insufficiency is a potentially lethal condition that is characterized by decreased production of glucocorticoids, mineralocorticoids and sex steroids. In normal conditions adrenocorticotropin and corticotrophin releasing hormone regulate cortisol production, but in critical illness other peptides and substances are produced that modulate the axis. In decompensated liver failure, there is a hemodynamic state similar to septic shock, even an increase in proinflammatory cytokines such as IL6 and TNF- alpha. In critically ill patients, a high proportion of adrenal insufficiency has been reported; therefore, some authors have argued that the same could happen in the cirrhotic patient, introducing the term hepatoadrenal syndrome. There are several reports of an increased frequency of adrenal insufficiency in the cirrhotic patient. However, these studies are heterogeneous in many aspects. There are differences in patient’s characteristics, in the criteria for the diagnosis of adrenal insufficiency, and in the laboratory tests used. Because over 90 percent of cortisol circulates bound to proteins, it is important to consider this issue in the diagnosis of adrenal insufficiency, especially in patients with hypoalbuminemia. Serum-free cortisol and salivary cortisol appear to be a good diagnostic method. Further studies need to be carried out in order to define the cut off points of these methods. These tests are not widely available.

La insuficiencia suprarrenal es una condición potencialmente letal, que se caracteriza por la disminución en la producción de glucocorticoides, mineralocorticoides y esteroides sexuales. Normalmente, la producción de cortisol es regulada por la adrenocorticotrofina y ésta por la hormona liberadora de corticotrofina, pero en estado de enfermedad, se producen otros péptidos y sustancias que modulan el eje. En la insuficiencia hepática descompensada, se produce un estado hemodinámico similar al shock séptico, incluso se produce un aumento de citoquinas proinflamatorias como IL6 y TNF- alfa. Como en el paciente crítico se ha reportado un gran porcentaje de insuficiencia adrenal, algunos autores han planteado que lo mismo podría ocurrir en el paciente cirrótico, introduciendo el término de síndrome hepatoadrenal. Varios autores han publicado que también existe un aumento en la frecuencia de insuficiencia adrenal en el paciente cirrótico. Sin embargo, en estos estudios la población analizada es heterogénea, se utilizan distintos criterios para definir insuficiencia adrenal y las pruebas de laboratorio utilizadas tienen limitaciones. Debido a que más del 90 por ciento del cortisol circula unido a proteínas, es importante considerar este factor para diagnóstico de la insuficiencia adrenal, especialmente en el paciente con hipoalbuminemia. En estos casos, el cortisol libre sérico parece ser junto al cortisol salival un buen método diagnóstico. Sin embargo, faltan estudios para definir los puntos de corte de estos exámenes y tienen la limitación que no están ampliamente disponibles.

Uso racional de corticoides en el paciente con shock séptico / Rational use of corticoids in a patient with septic shock

Introduction: Septic shock (SS) is a significant cause of mortality in NICUs. Objective: Review current knowledge on Hypothalamic-Pituitary-Adrenal Axis (HPA) and the scientific support for the use of gluco-corticoids in the use of this clinical picture. We know that the patient's ability to evolve into improvement or worsening depends upon the ability of the HPA axis to develop and sustain an adequate response to the stress provoked by SS. In some patients, due to many reasons, the prolongation of SS leads to a deficit of cortisol those results in functional acute adrenal insufficiency. Cortisol levels do not respond to ACTH stimulation test. There is no consensus among authors as to what is a normal concentration of cortisol during stress, or even if it is correlated with death among children with SS. The American College of Critical Care Medicine guidelines for SS in Pediatrics and Neonatology have made some recommendations for use of hydrocortisone.

Introducción: El shock séptico (SS) es una de las mayores causas de mortalidad en unidades de cuidados intensivos pediátricas. Objetivo: Revisar qué sabemos hasta ahora del papel que juega el eje hipotálamo-pituitaria-adrenal (HPA) en el SS y si hay evidencia científica que apoye el uso de glucocorticoides en el transcurso de este cuadro. Sabemos que de la habilidad del eje HPA para montar y sostener en el tiempo una adecuada respuesta al stress provocado por un SS dependerá si el paciente evoluciona a la mejoría o se agrava. En algunos pacientes debido a múltiples mecanismos, la prolongación del SS puede llevar a un déficit de cortisol, resultando en una insuficiencia adrenal aguda o funcional, la que se reflejaría en que los niveles de cortisol no responderían con un incremento significativo frente a una prueba de estimulo con ACTH. Entre los diversos reportes revisados, no existe consenso sobre cual sería la concentración "normal" de cortisol durante el stress y más aun no está claro si esto se correlacionaría con la mortalidad en el caso de los niños. Las guías de shock séptico en pediatría y neonatología del American College of Critical Care Medicine recomiendan en que tipo de pacientes con SS se debiera considerar tratamiento con hidrocortisona.

A study on endocrine changes in patients in intensive care unit.

Pattern of endocrine changes in moderate to severely ill patients in a medical intensive care unit, correlation with the severity of illness and whether these changes can predict outcome of the critically ill patients were evaluated and studied in 80 patients admitted with acute physiology and chronic health evaluation (APACHE) II score >10 and without any pre-existing endocrinopathies or on drugs likely to affect the endocrine axis. Adrenal insufficiency was present in 45%, and mortality was higher in those with lower (<15 microg/dl) and higher (>30 microg/dl) serum cortisol. Sick euthyroid syndrome was detected in 80%, and those with low mean T3 (<0.6 ng/ml), free T4 (<0.89 ng/dl) and total T4 (<4 microg/dl) and had increased mortality. Hypotestosteronaemia was found in 92% of men and was significantly associated with severity of illness in men. Though prolactin is the first hormone to be elevated, there was no correlation between prolactin and severity of illness or mortality.

Evaluation of adrenal function in long standing pulmonary Tuberculosis a study of 100 cases

Tuberculosis is a major public health problem in Pakistan and adrenal involvement in long-standing tuberculosis has been found to be common. A multi-center study was conducted to assess the adrenal function using short Synacthen test in one hundred patients with tuberculosis of more than 6 months duration at three hospitals of Rawalpindi and Islamabad. Forty patients demonstrated impaired response to Synacthen test. In 21 [52.5%] the increment from basal level was less than 300 nmol/L with a peak level increasing to over 600 mmol/L in 15 [37.5%] patients, the increment from basal level was less than 300 nmol/L as well as the peak level was also less than 600 nmol/L. In 4 [10%] patients the increment was more than 300 nmol/L but they were not able to obtain a peak level of 600 nmol/L. No significant difference was found between the patients with normal response and the impaired response with regards to their clinical features, duration of illness, body mass index [BMI], blood pressure variation and routine biochemical profile. It is concluded that adrenal dysfunction is common in patients with long-standing tuberculosis. Diagnosis of hypoadrenalism is not possible on clinical grounds and routine biochemical examinations. Synacthen stimulation test is necessary for its diagnosis

Hipocortisolismo por déficit selectivo de CRH de resolución espontánea: análisis de un caso / Hypocortisolism related to selective deficiency of CRH with spontaneous resolution: a case analysis

Hypocortisolism derived from hypothalamic deficiency of corticotropin releasing hormone is a highly unusual cause of adrenal insufficiency and its pathogenesis is still not fully understood. We report a mildly symptomatic patient having repeated low basal plasma cortisol levels with normal cortisol response to ACTH and lisine-vasopresine; however, she showed a clearly limited response to deep hypoglycemia, while GH reached a normal concomitant response. After 7 years of cortisol replacement the endogenous cortisol returned spontaneously to normality. The rest of pituitary function has been always normal