Miliary Tuberculosis with Addisons Disease - in old case of pulmonary tuberculosis, and tuberculosis of seminal vesicles - A rare case report

Addison's disease is a rare endocrinal disorder that was first described by Thomas Addison in 1855. Addison抯 disease occurs as a result of a lack of production of adrenocortical hormones, which is a rare but fatal disease if left untreated. The two most common causes of Addison's disease are autoimmune adrenalitis and tuberculosis which refer to hypoadrenalism caused by total or near total destruction or dysfunction of both adrenal cortices. Usual manifestations involve chronic fatigue, muscle weakness, loss of appetite, nausea, vomiting, diarrhoea, hypotension, and hyper pigmentation of the skin. A substantial proportion of patients presenting with extra-pulmonary tuberculosis (TB) have urogenital TB (UG-TB), which is easily under diagnosed because of non-specific symptoms, which are chronic and have cryptic protean clinical manifestations. Most of the clinician are not aware of the possibility of UG � TB. Calcification of seminal vesicle found in this case is a rare condition, which is commonly associated with diabetes, hyperparathyroidism, and genitourinary tuberculosis. We here in report a rare case of adrenal insufficiency due to miliary tuberculosis involving adrenal gland, old pulmonary tuberculosis and genitourinary tuberculosis (seminal vesicles calcification) in a 31 year old male person. He presented with multiple episodes of vomiting, and giddiness which wasalso accompanied with atypical hyperpigmentation. His symptoms resolved after starting anti tuberculous therapy.

Progress of late-onset circulatory collapse in preterm infants / 国际儿科学杂志

Late-onset circulatory collapse(LCC)in preterm infants is characterized by sudden onset of hypotension and/or oliguria after the first week of life, which is resistant to volume expanders and inotropes but responds rapidly to timely glucocorticoids treatment.LCC should be managed promptly and properly, or it may cause respiratory, digestive complications and life-long neurological problems.Relative adrenal insufficiency is considered the most likely cause of LCC, but its pathophysiology remains unclear.This review summarizes the current reserch about LCC regarding its pathophysiology, clinical features, diagnosis, treatment, and prognosis.

Crisis adrenal neonatal secundaria a hipoplasia hipofisaria / Neonatal Adrenal Crisis Secondary to Pituitary Hypoplasia

Introducción: La insuficiencia adrenal hipotálamo hipofisaria usualmente se manifiesta secundaria a tumores y, cuando resulta congénita se asocia, con frecuencia, con otras deficiencias hormonales. La crisis adrenal suele presentarse en su debut y puede resultar potencialmente mortal. Objetivo: Examinar el caso de una paciente con insuficiencia adrenal central que debutó con una crisis adrenal congénita. Presentación del caso: Recién nacida a término, padres no consanguíneos, hospitalizada a los 9 días de vida por clínica de una semana con múltiples episodios eméticos y apnea. Ingresó con deshidratación severa, hipotensa y estuporosa. Además, se encontró acidosis metabólica severa, hipoglucemia persistente, hiponatremia e insuficiencia prerrenal. Ante la no mejoría de su estado hemodinámico, a pesar del uso de cristaloides y vasopresores, finalmente mejoró con la administración de dosis altas de hidrocortisona. El diagnóstico de deficiencia de cortisol de origen central se realizó con un test dinámico de insulina y la resonancia magnética nuclear hipofisaria. Conclusiones: La crisis adrenal se debe tener presente como diagnóstico diferencial en episodios agudos con inestabilidad hemodinámica persistente e hipoglucemia de difícil manejo. Adicionalmente, hay que considerar que existen otras causas menos comunes de insuficiencia adrenal en neonatos como la hipoplasia hipofisaria(AU)

Introduction: Hypothalamic-pituitary adrenal insufficiency usually manifests secondary to tumors and, when congenital, is often associated with other hormonal deficiencies. Adrenal crisis usually occurs at its onset and can be life threatening. Objective: To review the case of a patient with central adrenal insufficiency who had an onset with a congenital adrenal crisis. Case presentation: Term newborn, non-consanguineous parents, hospitalized at 9 days of life for a week-long clinical presentation with multiple emetic episodes and apnea. She was admitted with severe dehydration, hypotensive and stuporous. In addition, severe metabolic acidosis, persistent hypoglycemia, hyponatremia and prerenal failure were found. Given the lack of improvement of her hemodynamic status, despite the use of crystalloids and vasopressors, she finally improved with the administration of high doses of hydrocortisone. The diagnosis of cortisol deficiency of central origin was made with a dynamic insulin test and pituitary nuclear magnetic resonance imaging. Conclusions: Adrenal crisis should be kept in mind as a differential diagnosis in acute episodes with persistent hemodynamic instability and difficult-to-manage hypoglycemia. Additionally, other less common causes of adrenal insufficiency in neonates, such as pituitary hypoplasia, should be considered(AU)

Advances in Hormone Replacement Therapy for Adult Adrenal Insufficiency / 罕见病研究

Adrenal insufficiency is a disease characterized by insufficient secretion of adrenocortical hormones, usually treated with glucocorticoid replacement therapy. The routine drugs have two forms-short-acting and long-acting. The shorter one should be taken 2-3 times a day resulting hormone level of patients fluctuating greatly within a day. Although long-acting drugs reduce the frequency of administration, it is easy to lead to excessive replacement, resulting in adverse effects on metabolism. New alternative treatments for adult patients have emerged, including modified-release hydrocortisone and hydrocortisone subcutaneous infusion pumps. In this review, we briefly introduce these new therapies, emphasizing the pharmacodynamics and pharmacokinetics of the replacement, the effects on metabolism and drug safety, aiming at contributing to the future clinical practice.

Central adrenal insufficiency: who, when, and how? From the evidence to the controversies - an exploratory review

ABSTRACT Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated.

Crisis suprarrenal: prevención, corticoterapia y elección del fármaco, revisión de la evidencia actual y recomendaciones / Adrenal crisis: prevention, corticotherapy and choice of the drug, review of current evidence and recommendations

INTRODUCCIÓN. La crisis suprarrenal se refiere a la insuficiencia suprarrenal aguda; la cual es un trastorno en el que la corteza adrenal no produce suficientes hormonas esteroides (en especial cortisol) para satisfacer las demandas del cuerpo, de acuerdo al mecanismo fisiopatológico se la puede clasificar como primaria, secundaria y terciaria, siendo más común en pacientes con insuficiencia suprarrenal primaria. Es una emergencia potencialmente mortal que requiere tratamiento inmediato. OBJETIVO. Establecer una estrategia de prevención y tratamiento de la crisis suprarrenal, así como la farmacoterapia ideal y sus alternativas válidas. MATERIAL Y MÉTODOS. Se realizó una revisión bibliográfica en varias revistas virtuales de alto carácter científico como Cochrane Library, Cochrane Systematic Reviews Database, MEDLINE a través de PubMed y ClinicalTrial.gov. Se seleccionaron revisiones sistemáticas con o sin metaanálisis, ensayos clínicos y recomendaciones de expertos relacionados con prevención y tratamiento de crisis suprarrenal en general. RESULTADOS. Se obtuvieron 1819 resultados, de los cuales se seleccionaron 20 artículos con mayor validez y replicabilidad en el medio para establecer un protocolo unificado de actuación. CONCLUSIÓN. El objetivo de la terapia es el tratamiento de la hipotensión y reversión de las anomalías electrolíticas y de la deficiencia de cortisol. Se deben infundir por vía intravenosa grandes volúmenes (1 a 3 litros) de solución salina al 0,9% o dextrosa al 5% en solución salina al 0,9% y la administración de hidrocortisona (bolo de 100 mg), seguido de 50 mg cada 6 horas (o 200 mg / 24 horas como infusión continua durante las primeras 24 horas). Si no se dispone de hidrocortisona, las alternativas incluyen prednisolona, prednisona y dexametasona.

INTRODUCTION. Adrenal crisis refers to acute adrenal insufficiency; which is a disorder in which the adrenal cortex does not produce enough steroid hormones (especially cortisol) to meet the body's demands, according to the pathophysiological mechanism it can be classified as primary, secondary and tertiary, being more common in patients with primary adrenal insufficiency. It is a life-threatening emergency that requires immediate treatment. OBJECTIVE. To establish a strategy for the prevention and treatment of adrenal crisis, as well as the ideal pharmacotherapy and its valid alternatives. MATERIAL AND METHODS. A literature review was performed in several highly scientific virtual journals such as Cochrane Library, Cochrane Systematic Reviews Database, MEDLINE through PubMed and ClinicalTrial.gov. Systematic reviews with or without meta-analysis, clinical trials and expert recommendations related to prevention and treatment of adrenal crisis in general were selected. RESULTS. A total of 1819 results were obtained, from which 20 articles with greater validity and replicability in the setting were selected to establish a unified protocol for action. CONCLUSIONS. The aim of therapy is the treatment of hypotension and reversal of electrolyte abnormalities and cortisol deficiency. Large volumes (1 to 3 liters) of 0.9% saline or 5% dextrose in 0.9% saline and administration of hydrocortisone (100 mg bolus), followed by 50 mg every 6 hours (or 200 mg / 24 hours as a continuous infusion for the first 24 hours) should be infused intravenously. If hydrocortisone is not available, alternatives include prednisolone, prednisone, and dexamethasone.

Diagnóstico de doença de Addison por meio de lesão cutânea na Atenção Primária: relato de caso / Addison's disease diagnosis based on a skin lesion in primary care: Case report / Diagnóstico de Enfermedad de Addison a través de lesión cutánea en la Atención Primaria: relato de caso

Introdução: A doença de Addison, ou insuficiência adrenal primária, é uma enfermidade insidiosa e rara, que pode apresentar altas taxas de morbimortalidade quando o seu diagnóstico não é reconhecido e o seu tratamento não é iniciado precocemente. Apresenta sintomas variados, entre os quais se destacam hipotensão arterial, hiperpigmentação cutânea, hiponatremia e hipercalemia. Quando não tratada, pode evoluir com crise adrenal e colapso cardiovascular. O diagnóstico da doença de Addison é feito clinicamente e por meio dos achados em exames laboratoriais, em que concentrações elevadas do hormônio adrenocorticotrófico e de baixas concentrações de cortisol no plasma caracterizam a insuficiência adrenal primária. O tratamento depende da causa e requer abordagem multidisciplinar, associado à reposição de glicocorticoides como também demais hormônios, quando necessário. Apresentação do caso: Este artigo descreve um caso de doença de Addison diagnosticada na Atenção Primária à Saúde, situação que não é comum, posto que a doença apresenta sintomas clínicos bastante inespecíficos, principalmente em seus estágios iniciais e, frequentemente, não é um diagnóstico considerado. Conclusão: Ao nível da Atenção Primária, o caso não obteve resolução completa, entretanto a instituição cumpriu com êxito o seu papel, firmado na Política Nacional de Atenção Básica, dispondo-se de ser a coordenadora do cuidado e ordenadora dos serviços de saúde, acolhendo o paciente e reconhecendo as suas necessidades.

Introduction: Addison's disease ­ also known as primary adrenal insufficiency ­ is an insidious and rare disease, which can have high rates of morbidity and mortality when its diagnosis is not identified, and treatment is not initiated early. It presents varied symptoms, among which hypotension, skin hyperpigmentation, hyponatremia, and hyperkalemia stand out. When left untreated, it can progress to adrenal crisis and cardiovascular collapse. Addison's disease is diagnosed clinically and through laboratory findings, with high concentrations of adrenocorticotropic hormone and low plasma cortisol concentrations characterizing primary adrenal insufficiency. The treatment depends on the cause and requires a multidisciplinary approach associated with glucocorticoid replacement as well as other hormones, when necessary. Case presentation: This article describes a case of Addison's disease diagnosed in primary care, an uncommon situation since the disease has very nonspecific clinical symptoms, especially in its early stages, and is not often considered in the diagnostic process. Conclusions: The case did not have a complete resolution at the primary care level; however, the facility successfully fulfilled its role, established in the National Primary Care Policy, as the care coordinator and organizer of health services, embracing the patient and recognizing their needs.

Introducción: La enfermedad de Addison, o insuficiencia suprarrenal primaria, es una enfermedad insidiosa y rara que puede presentar altas tasas de morbi-mortalidad cuando su diagnóstico no es reconocido y su tratamiento no se inicia prematuramente. Presenta síntomas variados, entre ellos se destaca hipotensión arterial, hiperpigmentación cutánea, hiponatremia e hiperpotasemia. Cuando no se trata, puede evolucionar una crisis adrenal y colapso cardiovascular. El diagnóstico de la enfermedad de Addison se hace clínicamente y a través de los hallazgos, en exámenes de laboratorio, en el que altas concentraciones de hormona adrenocorticotrópica (ACTH) y bajas concentraciones de cortisol en plasma caracterizan la insuficiencia Suprarrenal Primaria. El tratamiento depende de la causa y requiere un enfoque multidisciplinario, pero en general se hace con reemplazo de glucocorticoides y, en ocasiones, otras hormonas. Presentación del caso: Este artículo describe un caso de Enfermedad de Addison diagnosticada en la Atención Primaria de Salud, situación que no es común, ya que la enfermedad presenta síntomas clínicos bastante inespecíficos, principalmente en sus etapas iniciales, y a menudo no es un diagnóstico considerado. Conclusiones: En el ámbito de la APS, o en caso de no obtener una resolución completa, sin embargo, la institución cumple con éxito su rol firmado en la Política Nacional de Atención Primaria, que se pone a disposición para ser coordinadora de la atención y organizadora de dos servicios de salud, acomodando o paciente y reconociendo sus necesidades.

Paracoccidioidomicosis diseminada en paciente inmunocompetente: reporte de caso / Disseminated Paracoccidioidomycosis in immunocompetent patient: case report

Resumen La Paracoccidioidomicosis (PCM) es una infección micótica endémica en Latinoamérica que se caracteriza por compromiso multiorgánico. El diagnóstico tardío y la diseminación sistémica favorecen complicaciones como falla respiratoria e insuficiencia suprarrenal que condicionan el desenlace del paciente. Se presenta el caso de un paciente de 51 años de edad, procedente de la costa pacífica colombiana, inmunocompetente con PCM diseminada a sistema nervioso central (SNC), pulmones y glándulas suprarrenales con debut clínico de síndrome neurológico. Durante estancia hospitalaria presenta pico febril, colapso hemodinámico, aci dosis metabólica severa e hiperlactatemia. Se hemocultivó e inició tratamiento antimicrobiano de amplio espectro con piperacilina-tazobactam (4.5 gr/IV cada 8 horas), vancomicina (15 mg/kg) más anfotericina B desoxicolato (1 mg/kg/dia) y se trasladó a unidad de cuidado intensivo. En la muestras de tejido suprarrenal se identificaron levaduras multigemantes de Paracoccidioides spp e inflamacion crónica granulomatosa. A los seis días posteriores a su ingreso, el paciente continuó con deterioro hemodinámico, desequilibrio electrolítico, shock séptico e insuficiencia suprarrenal que conllevó a su deceso a pesar de las medidas terapéuticas establecidas. Se intenta exponer el desafío que representa el diagnóstico de PCM sistémica y promover su sospecha clínica para poder identificar la enfermedad de forma oportuna y evitar complicaciones que conduzcan a un desenlace fulminante.

Abstract Paracoccidioidomycosis (PCM) is an endemic fungal infection in Latin America characterized by multi-organ involvement. Late diagnosis and systemic dissemina tion favor complications such as respiratory failure and adrenal insufficiency, which determine the outcome of the patient. We present the case of a 51-year-old patient from the Colombian Pacific coast, immunocompetent with PCM spread to the central nervous system (CNS), lungs, and adrenal glands with a clinical debut of the neurological syndrome. During a hospital stay, he presented fever peak, hemodynamic collapse, severe metabolic acidosis, and hyperlactatemia. Blood culture and began broad-spectrum antimicrobial treatment with piperacillin-tazobactam (4.5 gr / IV every 8 hours), vancomycin (15 mg/kg) plus amphotericin B deoxycholate (1 mg/kg/day) and was transferred to the intensive care unit. Paracoccidioides spp multigene yeasts and chronic granulomatous inflammation were identified in adrenal tissue samples. Six days after admission, the patient continued with hemodynamic deterioration, electrolyte imbalance, septic shock, and adrenal insufficiency that led to death despite the established therapeutic measures. The aim is to expose the challenge posed by the diagnosis of systemic PCM and promote its clinical suspicion to identify the disease promptly and avoid complications that lead to a fulminant outcome.

Bilateral adrenal hemorrhage caused by anticoagulant therapy after joint replacement surgery: One case report and literature review / 中华内分泌代谢杂志

Bilateral adrenal hemorrhage is a rare cause of primary adrenal insufficiency, and bilateral adrenal hemorrhage due to anticoagulant use is even rarer. We describe the case of a 62-year-old woman receiving post total knee arthroplasty anticoagulant therapy who presented fever, vomitting, stomachache, and severe fatigue on the 8th day. It was until 4 months later that the patient was finally diagnosed with adrenal insufficiency resuting from bilateral adrenal hemorrhage, her symptoms were relieved by glucocorticoid replacement therapy. In order to promote the awareness, diagnosis, and mangement of post-surgery anticoagulants induced bilateral adrenal hemorrhage, the clinical characteristics of the reported cases were summarized and analyzed.

Presentación diversa de las enfermedades de la corteza adrenal

RESUMEN Introducción: Las glándulas suprarrenales se dividen en corteza y médula. La corteza secreta tres clases de hormonas diferentes: los glucocorticoides, mineralocorticoides y andrógenos; la médula produce las catecolaminas. Todas ellas intervienen en múltiples funciones corporales. Objetivo: Mostrar diferentes formas de presentación de algunas de las enfermedades de la corteza adrenal. Presentación de los casos: Paciente 1: escolar de 7 años, antecedentes de hipotiroidismo controlado, presenta decaimiento y escaso crecimiento pondoestatural. Cortisol en ayunas 86 nmol/L y ACTH 154 pg/ml. Se diagnostica insuficiencia adrenal primaria. Reingresa a los 9 años, por mantener escaso crecimiento. Edad ósea: 2 años y 8 meses. Test de clonidina: alterado, confirma déficit de hormona del crecimiento. Paciente 2: escolar de 8 años, antecedentes de hiperplasia adrenal congénita por déficit de 21 hidroxilasa, forma virilizante simple. Presenta aceleración del desarrollo genital. Se incumplió tratamiento con hidrocortisona, durante 5 años. Se comprobó elevada la 17 hidroxiprogesterona 189 ng/dl. Se diagnosticó pubertad precoz periférica y virilización de los genitales. Paciente 3: lactante de 5 meses con obesidad de 3 meses de evolución. Tomografía axial computarizada de abdomen contrastado confirma lesión tumoración de 5 cm en proyección de la suprarrenal derecha. Cortisol en ayunas 892 nmol/L, cortisol 11 pm 920 nmol/L. Se realizó cirugía y se diagnosticó síndrome de Cushing por carcinoma adrenal productor de cortisol. Conclusiones: En la práctica clínica diaria podemos encontrar pacientes con síntomas y signos tan comunes como el decaimiento, vómitos o el aumento brusco de peso y ellos ser secundario a enfermedades de la glándula suprarrenal.

ABSTRACT Introduction: The adrenal glands are divided into cortex and marrow. The cortex secretes three different classes of hormones: glucocorticoids, mineralocorticoids and androgens; the marrow produces catecholamines. All of them are involved in multiple corporal functions. Objective: Show different forms of presentation of some of the diseases of the adrenal cortex. Presentation of cases: Patient 1: 7-year-old school boy, history of controlled hypothyroidism, and presenting decay and poor pondostatural growth. Cortisol level in fasting 86 nmol/L and ACTH 154 pg/ml. Primary adrenal insufficiency is diagnosed. Re-admitted at age 9 for maintaining little growth. Bone age: 2 years and 8 months. Clonidine test: altered, it confirms growth hormone deficiency. Patient 2: 8-year-old schoolboy, history of congenital adrenal hyperplasia due to 21 hydroxylase deficiency, simple virilizing form. He presents acceleration of genital development. Hydrocortisone treatment was missed for 5 years. 17 hydroxyprogesterone was found to be elevated to 189 ng/dl. Peripheral precocious puberty and virilization of the genitals were diagnosed. Patient 3: 5-month-old infant with obesity of 3 months of evolution. Contrasted computed axial tomography of the abdomen confirms tumor lesion of 5 cm in projection of the right adrenal. Cortisol level in fasting 892 nmol/L, cortisol 11 pm 920 nmol/L. Surgery was performed and Cushing's syndrome was diagnosed due to cortisol-producing adrenal carcinoma. Conclusions: In daily clinical practice we can find patients with symptoms and signs as common as decay, vomiting or sudden weight gain and they are secondary to diseases of the adrenal gland.

Síndrome de Cushing secundario a administración tópica decorticoesteroides / Cushing Syndrome due to topical corticosteroid misuse

Los corticoesteroides tópicos son drogas muy comunes, frecuentemente utilizadas en patologías dermatológicas. Su mal uso puede causar efectos sistémicos, como el síndrome de Cushing y la supresión del eje hipotalámico ­ hipofisiario ­ adrenal. Presentamos un caso de un lactante menor de siete meses quien desarrolla un síndrome de Cushing secundario al uso de Clobetasol por una dermatitis en el área del pañal, por tiempo prolongado, sin prescripción médica. Al examen físico se evidencia obesidad a predominio central, con fascie de luna llena, hipertricosis en región frontal, telangiectasias aisladas en mejillas y cuello de búfalo. Los paraclínicos demuestran una hipercolesterolemia, hipertrigliceridemia, elevación de las transaminasas y cortisol sérico en la mañana disminuido. Se concluye que se debe informar a los padres de los efectos adversos sistémicos de los esteroides tópicos y se sugiere evitar en pacientes pediátrico(AU)

Topical corticosteroids are very common drugs used in the treatment of inflammatory skin diseases. Prolonged ormisuse of them may cause systemic adverse effects, including Cushing syndrome and hypothalamic-pituitary-adrenal axissuppression. We present a case of a seven months old maleinfant who developed iatrogenic Cushing syndrome after diaperdermatitis treatment through misuse of Clobetasol, withoutdoctor's prescription. We observe redness and a moon face, abuffalo hump, central obesity and hirsutism. Laboratory values revealed hypercholesterolemia, hypertriglyceridemia, elevationin liver enzymes and low early morning cortisol. To conclude,parents must be informed by physicians about the adverse effect of steroids and the should be avoided in very young infant(AU)

Crisis adrenal asociada al uso de modafinilo / Adrenal crisis associated with modafinil use

Resumen La crisis adrenal es la forma más extrema de presentación de la insuficiencia adrenal y representa una urgencia endocrinológica que llega a poner en riesgo la vida. Esta situación puede ser des encadenada por diferentes causas, entre las cuales se incluye el uso de fármacos inductores del CYP3A4, que aceleran la depuración de la hidrocortisona. Describimos el caso de una mujer de 85 años, con antecedentes de insuficiencia adrenal secundaria y enfermedad renal crónica, que presentó síntomas compatibles con crisis adrenal (astenia, adinamia, hiponatremia grave con síntomas neurológicos e hipotensión arterial) luego de nueve días del inicio de tratamiento con modafinilo. El cuadro clínico mejoró rápidamente con la suspensión del modafinilo y la administración de hidrocortisona endovenosa. Luego de descartar las posibles causas desencadenantes (infecciosas, isquémicas, tromboembolismo pulmonar y omisión en la toma de hidrocortisona), se interpretó que el modafinilo precipitó los síntomas de insuficiencia adrenal al aumentar la depuración del corticoide. El modafinilo tiene la capacidad de inducir la actividad del CYP3A4 y, en consecuencia, disminuir la biodisponibilidad de la hidrocortisona. Recalcamos la necesidad de ajustar la dosis de reemplazo de corticoides en sujetos que reciben fármacos inductores del metabolismo.

Abstract Adrenal crisis is the most extreme presentation form of adrenal insufficiency and represents a life-threatening endocrinological emergency. This situation can be triggered by different causes including the use of CYP3A4-inducing drugs, which accelerate hydrocortisone clearance. We describe the case of an 85-year-old woman with secondary adrenal insufficiency and chronic renal disease, who presented symptoms compatible with adrenal crisis (asthenia, adynamia, severe hyponatremia associated with neurological symptoms and hypotension) nine days after the start of modafinil treat ment. The clinical picture improved rapidly with the suspension of modafinil and the administration of intravenous hydrocortisone. After ruling out the possible triggering causes (infectious, ischemic, pulmonary thromboembo lism and failure to take hydrocortisone), it was interpreted that modafinil precipitated the symptoms of adrenal insufficiency by increasing the steroid clearance. Modafinil has the ability to induce the activity of CYP3A4 and consequently decrease the bioavailability of hydrocortisone. We emphasize the need to adjust steroid dose re placement in subjects receiving metabolism-inducing drugs.

Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia

ABSTRACT Primary adrenal insufficiency (PAI) is characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. Addison's disease (AD) and congenital adrenal hyperplasia (CAH) are the most frequent disorders in adults and children, respectively. Despite the diagnostic advances and the availability of glucocorticoid and mineralocorticoid replacements, adrenal crisis (AC) is still a potentially lethal condition contributing to the increased mortality, not only during the first year of life, but also throughout life. Failure in increasing glucocorticoid doses during acute stress, when greater amounts of glucocorticoids are required, can lead to AC and an increase morbimortality rate of PAI. Considering a mortality rate of 0.5 per 100 patient years, up to 1,500 deaths from AC are expected in Brazil in the coming decade, which represents an alarming situation. The major clinical features are hypotension and volume depletion. Nonspecific symptoms such as fatigue, lack of energy, anorexia, nausea, vomiting, and abdominal pain are common. The main precipitating factors are gastrointestinal diseases, other infectious disease, stressful events (e.g., major pain, surgery, strenuous physical activity, heat, and pregnancy), and withdrawal of glucocorticoid therapy. Suspected AC requires immediate therapeutic action with intravenous (iv) hydrocortisone, fluid infusion, monitoring support, and antibiotics if necessary. AC is best prevented through patient education, precocious identification and by adjusting the glucocorticoid dosage in stressor situations. The emergency card, warning about acute glucocorticoid replacement, has high value in reducing the morbidity and mortality of AC.

Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia / Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

Enfermedad de addison e insuficiencia adrenal aguda: presentación de un caso y revisión de la literatura / Addison disease and acute adrenal insufficiency: case report and literature review

La enfermedad de Addison es una patología endocrinológica ocasionada por la disminución en la secreción de hormonas esteroideas por parte de la corteza adrenal; debida a múltiples etiologías (más comúnmente la tuberculosis en países en vías de desarrollo); con una evolución lenta, insidiosa y progresiva. Pudiendo llegar a una insuficiencia adrenal aguda, misma que puede llegar a ser de extrema gravedad; y en caso de no ser diagnosticada y tratada adecuadamente puede llevar a la muerte. El tratamiento primordial lo constituye la terapia hormonal sustitutiva con fármacos corticoesteroideos.

Addison's disease is an endocrinological pathology caused by the decrease in the secretion of steroid hormones by the adrenal cortex, due to multiple etiologies (most commonly tuberculosis in developing countries); with a slow, insidious and progressive evolution. Being able to reach an acute adrenal insufficiency, which can become extremely serious, and if it is not diagnosed and treated properly, it can lead to death. The primary treatment is hormone replacement therapy with corticosteroid drugs

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Adrenal axis in critical illness / Eje adrenal en la enfermedad crítica

Abstract After a stressful event, adaptative mechanisms are carried out to support vital functions. Hypothalamic-pituitary-adrenal axis plays a key role in stress response regulating metabolism, cardiovascular function and immune system. This review addresses pathophysiological changes of the adrenal axis during critical illness, recognizing limitations of methods applied for its evaluation in this special context and defining indications for corticosteroid replacement in critically ill patients. The concept of relative adrenal insufficiency should be abandoned; cosyntropin stimulation test should not be performed for diagnosis of adrenal insufficiency in critical illness nor for establishing the need of treatment.

Resumen Diversos mecanismos adaptativos se ponen en marcha para sostener las funciones orgánicas vitales en el paciente crítico. El eje hipotálamo-hipófiso-adrenal tiene un papel clave en la respuesta al estrés al regular el metabolismo, la función cardiovascular y la respuesta inmune. Esta revisión tiene por objetivos analizar los cambios fisiopatológicos que se producen en el eje adrenal durante la enfermedad crítica, reconocer las limitaciones de los métodos diagnósticos y definir indicaciones de tratamiento de reemplazo corticoideo en este contexto. El concepto de insuficiencia adrenal relativa debe ser descartado y no se recomienda el test de estímulo con cosintropina para diagnóstico de insuficiencia adrenal durante enfermedad crítica ni para definir la necesidad de tratamiento.

Consideraciones en el manejo del adulto con Hiperplasia Suprarrenal congénita clásica por déficit de 21-Hidroxilasa / Management considerations for the adult with congenital adrenal hyperplasia due 21-hydroxylase deficiency

La Hiperplasia Suprarrenal Congénita (HSRC) corresponde a un grupo de defectos genéticos en la síntesis de cortisol. El 95% de ellas son debidas al déficit de 21-hidroxilasa por lo que nos referiremos solo a esta deficiencia. La hiperplasia suprarrenal congénita clásica (HSRC-C) debuta en recién nacidos o lactantes con insuficiencia suprarrenal primaria, diferentes grados de hiperandrogenismo clínico en mujeres y puede coexistir con hipotensión, hiperkalemia e hiponatremia si hay un déficit clínico de aldosterona. El objetivo de este artículo es actualizar el conocimiento y enfoques sugeridos para el manejo de la HSRC-C desde el inicio de sus controles en la etapa adulta. El diagnóstico diferencial en retrospectiva de la HSRC-C y la no clásica (HSRC-NC) a veces resulta difícil ya que esta enfermedad es un espectro fenotípico continuo. La insuficiencia suprarrenal y la dependencia a terapia corticoidal son los eventos principales para diferenciar estas dos patologías que tienen enfoques terapéuticos diferentes. El tratamiento de la HSRC-C en adultos abarca 2 objetivos primarios: la adecuada sustitución de la falla suprarrenal y el control de hiperandrogenismo mediante el uso de corticoides en sus dosis mínimas efectivas. En la mujer existen terapias complementarias para el control del hiperandrogenismo como anticonceptivos y otras que se encuentran en diferentes fases de investigación. Esto permite disminuir las dosis de corticoides en algunos casos. Es importante a la vez abordar tres objetivos secundarios: controlar el riesgo cardiometabólico propio de la enfermedad, evitar el sobre tratamiento corticoidal y manejar la infertilidad. La correcta monitorización del tratamiento en adultos tomando en cuenta los objetivos descritos permite una mejor calidad de vida en estos pacientes. Finalmente el consejo genético debe realizarse en todos los pacientes con HSRC que deseen fertilidad y en sus parejas. El estudio requiere de secuenciación del gen CYP21A2 y debe realizarse en un laboratorio de experiencia.

Congenital Adrenal Hyperplasia (CAH) are a group of genetic defects characterized by impaired cortisol synthesis. 95% of them are due to 21-hydroxylase deficiency. We will discuss only this enzyme's deficiency. Classic congenital adrenal hyperplasia (CAH-C) debuts in newborns or infants with primary adrenal insufficiency, some degree of clinical hyperandrogenism in newborn females, and can coexist with hypotension, hyperkalemia, and hyponatremia if there is a clinical aldosterone deficiency. The objective of this article is to update the knowledge and suggested approaches for the management of CAH-C from the beginning of its controls in the adult stage. The retrospective differential diagnosis of CAH-C and non-classical (CAH-NC) is sometimes difficult because this disease is a continuous phenotypic spectrum. Adrenal insufficiency and dependence on corticosteroid therapy are the main events to differentiate these two pathologies that have different therapeutic approaches. In adults, the treatment of CAH-C must include 2 primary objectives: adequate the replacement of adrenal failure and control of hyperandrogenism, through the use of corticosteroids in their minimum effective doses. In women there are complementary therapies for the control of hyperandrogenism, such as contraceptives and others that are in different phases of research. This makes it possible to reduce the doses of corticosteroids in some cases. It is important at the same time to address three secondary objectives: control the cardiometabolic risk of the disease secondary to corticosteroid treatment, avoid corticosteroid overtreatment and manage infertility. The correct monitoring of treatment in adults and taking in to account the objectives described, allows a better quality of life in these patients. Finally, genetic counseling must be carried out in all patients planning for children, with any type of CAH and in their partners. The study requires sequencing of the CYP21A2 gene and must be performed in a certified laboratory.

Efectos de los opioides en endocrinología / Opioids effects in endocrinology

El uso de opioides ha aumentado en forma significativa en las últimas décadas, lo que nos ha permitido conocer sus diversos efectos en el sistema endocrino. Estos efectos están sub diagnosticados, en parte porque los síntomas se confunden con los de la misma enfermedad que lleva al uso de opioides y porque no los buscamos de forma dirigida. El hipogonadismo y la insuficiencia suprarrenal son sus efectos más establecidos, sin embargo, otros efectos como los provocados en el tejido óseo requieren de especial atención. La evaluación de los ejes gonadotropo, adrenal y de la salud ósea debe tenerse en consideración en los usuarios crónicos de opioides, particularmente frente a la presencia de síntomas. La suspensión o reducción del uso de opioides es el primer tratamiento del compromiso endocrinológico.

The use of opioids has increased significantly in recent decades, which has allowed us to understand its effects on the endocrine system. These effects are underdiagnosed, the symptoms are confused with those of the same disease that leads to the use of opioids and we do not look for them in a targeted way. Hypogonadism and adrenal insufficiency are its most established effects, however, other effects such as the ones caused on bone tissue require special attention. Evaluation of gonadotropic and adrenal axes as well as bone health should be taken into consideration in chronic opioid users, particularly in the presence of symptoms. Stopping or reducing opioid use is the first treatment for endocrine compromise.