Manejo de pacientes con Síndrome de Cushing

El exceso crónico de glucocorticoides se acompaña de una amplia variedad de signos y síntomas conocidos como síndrome de Cushing. Esta condición, ocurre con mayor frecuencia por causas iatrogénicas cuando los glucocorticoides son usados como terapia antiinflamatoria por tiempo prolongado. El mecanismo patogénico del Cushing endógeno puede dividirse en dependiente o independiente de ACTH. A pesar de los avances en el diagnóstico y tratamiento de esta patología, el síndrome de Cushing continúa siendo un reto para el clínico. En este artículo, basado en niveles de evidencia científica y en la experiencia clínica de la Unidad de Endocrinología del IAHULA, se presenta el protocolo de manejo del Síndrome de Cushing, el cual incluye criterios diagnósticos, manejo clínico y tratamiento de esta condición.

Chronic glucocorticoid excess is accompanied by a wide range of signs and symptoms known as Cushing’s syndrome. This condition most commonly arises from iatrogenic causes when glucocorticoids have been used as anti-inflammatory treatment for a long time. The pathogenetic mechanism of endogenous Cushing’s syndrome can be divided into ACTH dependent and ACTH independent. Despite major advances in diagnosis and therapy, Cushing’s syndrome is frequently a challenge for the clinician. In this paper, based on levels of scientific evidence and clinical experience in the Unit of Endocrinology, IAHULA, we present the protocol for the management of Cushing’s syndrome, which includes: diagnostic criteria, clinical management and treatment of this condition.

Características clínicas y epidemiológicas del síndrome de cushing. Medellín, 1986-2010 / Clinical and epidemiological features of cushing’s syndrome. Medellín, 1986-2010

Introducción: El síndrome de Cushing, aunque poco frecuente, se asocia a una morbimortalidad significativa.En nuestro medio, no se cuenta aún con estudios que reporten las características clínicas y epidemiológicas de esta entidad. Por esta razón, en este estudio se describen los datos recopilados durante 24 años en 30 pacientes con síndrome de Cushing en la ciudad de Medellín, Colombia. Métodos:Estudio descriptivo retrospectivo, donde se evaluó el diagnóstico, tratamiento y desenlaces de pacientes con síndrome de Cushing, atendidos entre mayo de 1986 y enero de 2010 en los servicios de Endocrinología de la Universidad de Antioquia, Hospital Universitario de San Vicente Fundación. Resultados:Se encontraron seis casos de síndrome de Cushing independiente de la hormona adrenocorticotropa (ACTH), cuatro de origen ectópico y 20 de origen hipofisario. En las pruebas bioquímicas, solo hubo diferencias significativas en la prueba de supresión con dosis altas de dexametasona en la enfermedadde Cushing.

Introduction: Although Cushing’s syndrome is an uncommon disease, it is associated with significant morbidity and mortality. Thus far, there are no reports of the clinical and epidemiological characteristicsof this entity in our country. Consequently, this study was conducted to analyze data collected over 24 years in 30 patients with Cushing’s syndrome in the city of Medellin, Colombia. Methods: A retrospective descriptive study was conducted to evaluate the diagnostic approach, treatment and outcomes of patients with Cushing’s syndrome between May, 1986 and January, 2010 in the Endocrinology Service at the University of Antioquia and in the Hospital Universitario San Vicente Fundación. Results: We found six cases of ACTH-independent Cushing’s syndrome, four ectopic tumors and 20 tumors of pituitaryorigin. Regarding biochemical tests, there was statistically significant difference in suppression test with high-dose dexamethasone in Cushing’s disease.

Síndrome de Cushing por adenomielolipoma. Presentación de caso / Cushing's syndrome caused by adenomyelolipoma. A case report

Se presenta el caso de una paciente de 61 años con antecedentes de dolor lumbar derecho con una irradiación al miembro inferior derecho que no se alivia con el reposo, ni analgésicos, de moderada intensidad, y 3 meses de evolución, debuta de hipertensión arterial, diabetes mellitus e incremento del peso corporal en la cara, tórax y abdomen, que contrasta con delgadez de las extremidades. Se decide el ingreso, siendo realizadas investigaciones indispensables, donde se demuestran las cifras de glucemia compatibles con diabetes mellitus, estudios imagenológicos, como la ultrasonografía de hemiabdomen superior donde se observa masa suprarrenal derecha en contacto con el hígado, tomografía axial computarizada simple y contrastada de suprarrenales que confirma resultado ultrasonográfico, ante esto se le realiza ritmo circadiano para el cortisol, que no se encontraba conservado, inhibiciones con 2 mgs y 8mgs de dexametasona, no existiendo inhibición, confirmándose síndrome de Cushing. Se decide adrenalectomía derecha y biopsia por congelación, que informa adenomielolipoma de 7 cms x 6 cms de suprarrenal derecha.

A 61-year old female patient with a history of right back pain with radiation to the right-lower limb, that did not relieve at rest or with the use analgesics of moderate intensity, having a 3-month evolution, presenting hypertension and diabetes mellitus onset, together with an increase in body weight mainly in her face, thorax and abdomen, which contrasted to the thinness of her extremities was admitted. The necessary clinical complementaries indicated high levels of blood glucose compatible with diabetes mellitus and the sonographic studies showed an adrenal mass in contact with the liver in the upper right hemi-abdomen, simple and contrasted CT of the adrenal glands confirmed the sonographic results, the circadian rhythm was driven to the cortisol control, resulting in not preserved. No inhibitions were observed with 2 mgs and 8mgs of dexamethasone. Cushing's syndrome was confirmed. Right adrenalectomy and freeze-biopsy were performed reporting an adenomyelolipoma of 7 cms x 6 cms of the right adrenal gland.

Hipocalemia persistente: relato de caso / Persistent hypokalemia: case report

JUSTIFICATIVA E OBJETIVOS: Os distúrbios do metabolismo do potássio são comuns e tanto a reposição como o diagnóstico etiológico da hipocalemia grave e refratária em pacientes internados são um grande desafio na prática clínica. A diminuição do potássio plasmático leva a um grande prejuízo na função de nervos e músculos, podendo resultar em arritmias graves, em que o paciente na maioria das vezes apresenta-se assintomático, ou com queixas inespecíficas, como fraqueza muscular. O objetivo deste estudo foi mostrar a dificuldade no diagnóstico etiológico da hipocalemia e trazer alternativas para simplificá-lo. RELATO DO CASO: Paciente do sexo masculino, 34 anos, técnico em enfermagem, que evoluiu com hipocalemia persistentee grave. No período de dois meses evoluiu com quadro de hipertensão arterial, e, posteriormente, acne, confusão mental e diabetes com baixos valores plasmáticos de potássio apesar da reposição vigorosa, por via oral e venosa, de cloreto de potássio. Após descartar o hiperaldosteronismo, investigou-se hipercortisolismo,apesar de discretos achados fenotípicos de síndrome de Cushing. Com a confirmação do diagnóstico de doença de Cushing, o mesmo foi submetido à adrenalectomia bilateral com rápida correção dos valores pressóricos, glicêmicos e de potássio sérico. CONCLUSÃO: Diante de um caso de hipocalemia grave e refratária à reposição, torna-se indispensável o estabelecimento do diagnóstico etiológico para a correção deste grave distúrbio metabólico.

BACKGROUND AND OBJECTIVES: Metabolic disorders of potassium are common and both the replacement and the etiology of severe and refractory hypokalemia in hospitalized patients are a major challenge in clinical practice. The decrease in plasma potassium leads to a large impairment of nerves and muscles function and can result in life-threatening arrhythmias, in which the patient is most often asymptomatic or presents with nonspecific complaints, such as muscle weakness. This study aims to show the difficulty in diagnosing the etiology of hypokalemia and bring alternatives to simplify it. CASE REPORT: Male patient, 34 years-old, technical nursing has developed severe and persistent hypokalemia. In a two-month period he progressed with hypertension, and later, acne, diabetes, mental confusion and low plasma levels of potassium despite vigorous oral and intravenous potassium chloride replacement. After discarding hyperaldosteronism, hypercortisolism was investigated, although discrete phenotypic findings of Cushing's syndrome were present. Just after confirmation of Cushing's disease, the patient has undergone bilateral adrenalectomy with rapid correction of blood pressure values serum glucose and potassium. CONCLUSION: Facing a case of severe hypokalemia refractory to potassium replacement, it is essential to establish an etiological diagnosis for the correction of this serious metabolic disorder.

Hipertensão arterial, osteoporose, amenorreia e depressão como manifestações da síndrome de cushing acth-independente: evolução após adrenalectomia laparoscópica / Arterial hypertension, osteoporosis, amenorrhea, and depression as presentation of ACTH-independent Cushing's syndrome: follow-up after laparoscopic adrenalectomy

A síndrome de Cushing é caracterizada por excesso de glicocorticóides circulantes. Os tumores suprarrenais secretores de cortisol representam a principal causa desse distúrbio, dentre os quais adenomas, que correspondem a 65% dos casos. A apresentação clínica típica inclui obesidade centrípeta, fadiga, hipertensão arterial de difícil controle, osteoporose, distúrbios menstruais, hirsutismo, equimoses e estrias violáceas. Entretanto, casos de síndrome de Cushing subclínica vem sendo descritos com frequência crescente, o que faz com que essa doença ainda representardesafio diagnóstico na atualidade, pela capacidade de mimetizar outras entidades nosológicas, tais como síndrome metabólica, depressão e alcoolismo. Relata-se o caso de uma mulher de 27 anos, que vinha em tratamento de hipertensão arterial, osteoporose e depressão intensa antes do diagnóstico de síndrome de Cushing ACTH-independente,na qual o tratamento cirúrgico da doença de base resultou abrandamento significativo das comorbidades.

Cushing’s syndrome is characterized by an excess of circulating glucocorticoids. Cortisol-secreting adrenal tumors are the most common cause of endogenous ACTH-independent disease, with adrenal adenomas accounting for 65% of these cases. The typical clinical presentation includes centripetal obesity, fatigue, arterial hypertension, osteoporosis, menstrual disorders, hirsutism, easy bruising, and diffuse violaceous striae. However, subclinical Cushing´s syndrome is being described with growing frequency, still making this disease a diagnostic challenge, due to the ability to mimicother nosologic entities, such as the metabolic syndrome, depression and alcoholism. The authors report the case of a 27-year-old woman, who has been treated for hypertension, osteoporosis and depression before the diagnosis of ACTH-independent Cushing’s syndrome was established, and in whom the surgical treatment of the disease resulted in significant improvement of co-morbidities.

Retirada da corticoterapia: recomendações para a prática clínica: [revisão] / Withdrawal from glucocorticosteroid therapy: clinical practice recommendations: [review]

OBJETIVO: Apresentar uma revisão atualizada e prática sobre como efetuar de forma segura a retirada da corticoterapia. FONTES DOS DADOS: Revisão da literatura utilizando os bancos de dados MEDLINE e LILACS (1997-2007), selecionando os artigos mais atuais e representativos do tema. SÍNTESE DOS DADOS: Três situações clínicas podem ocorrer durante a retirada da corticoterapia prolongada: insuficiência adrenal secundária à supressão do eixo hipotálamo-hipófise-adrenal, síndrome de retirada ou deprivação dos corticóides e reativação da doença de base. Embora não exista consenso sobre o melhor esquema para descontinuar a terapia prolongada com corticóides, existe concordância quanto ao fato desta retirada ser gradual. Este artigo atualiza o pediatra quanto ao reconhecimento desses problemas e fornece orientações para a suspensão do tratamento prolongado com corticóide. Uma breve revisão da farmacologia dos corticóides também é descrita. CONCLUSÃO: Não existe teste com bom valor preditivo para antecipar o risco de insuficiência adrenal nos pacientes que receberam terapia crônica com corticóide. São necessários estudos prospectivos para avaliar a real incidência desse problema e assim propor estratégias racionais para sua prevenção. No momento, a menos que a integridade do eixo hipotálamo-hipófise-adrenal esteja estabelecida por testes dinâmicos, recomenda-se a administração de corticóide em situações de estresse nos pacientes que fizeram uso de corticoterapia crônica e/ou em doses elevadas.

OBJECTIVE: To present an up-to-date and practical review of how to safely withdraw glucocorticosteroid therapy. SOURCES: A review of the published literature identified by searching the MEDLINE and LILACS databases (1997-2007), selecting the most representative articles on the subject. SUMMARY OF THE FINDINGS: Three clinical situations may occur during glucocorticoid withdrawal: adrenal insufficiency secondary to negative feedback on the hypothalamic-pituitary adrenal (HPA) axis, steroid withdrawal syndrome and relapse of the disease for which the glucocorticoids were prescribed. Although there is no consensus on how to best discontinue prolonged glucocorticosteroid therapy, there is agreement that this withdrawal should be gradual. This article updates pediatricians on how to recognize these problems and provides recommendations on how to safely suspend glucocorticosteroid therapy. A brief review of the pharmacology of glucocorticoids is also presented. CONCLUSION: There is no good predictive test for predicting the risk of adrenal insufficiency in patients who have been on corticosteroid therapy chronically. There is a need for prospective studies to assess the true incidence of this problem and to propose rational strategies for preventing it. The current recommendation is that patients who have been on chronic and/or high dose glucocorticoids should be administered glucocorticoids during stress situations unless the integrity of the HPA axis has been established by dynamic tests.

Increased diagnostic probability of subclinical cushing’s syndrome in a population sample of overweight adult patients with type 2 diabetes mellitus

Endogenous Cushing’s Syndrome (CS) is unusual. Patients with subclinical CS (SCS) present altered cortisol dynamics without obvious manifestations. CS occurs in 2-3 percent of obese poorly controlled diabetics. We studied 103 overweight adult outpatients with type 2 diabetes to examine for cortisol abnormalities and SCS. All collected salivary cortisol at 23:00 h and salivary and serum cortisol after a 1 mg dexamethasone suppression test (DST). Patients whose results were in the upper quintile for each test (253 ng/dL, 47 ng/dL, and 1.8 mg/dL, respectively for the 23:00 h and post-DST saliva and serum cortisol) were re-investigated. Average values from the upper quintile group were 2.5-fold higher than in the remaining patients. After a confirmatory 2 mg x 2 day DST the investigation for CS was ended for 61 patients with all normal tests and 33 with only one (false) positive test. All 8 patients who had two abnormal tests had subsequent normal 24h-urinary cortisol, and 3 of them were likely to have SCS (abnormal cortisol tests and positive imaging). However, a final diagnosis could not to be confirmed by surgery or pathology. Although not confirmatory, the results of this study suggest that the prevalence of SCS is considerably higher in populations at risk than in the general population.

A síndrome de Cushing (SC) endógena é rara. Pacientes com SC subclínica (SCS) apresentam hipercortisolismo sem manifestações clínicas. SC ocorre em 2-3 por cento de diabéticos mal controlados. Estudamos 103 pacientes adultos obesos ambulatoriais com diabetes mellitus tipo 2 para avaliar alterações do cortisol e SCS. Todos coletaram cortisol salivar às 23:00 h e cortisol salivar e sérico após teste de supressão com 1 mg de dexametasona (DST). Pacientes cujos resultados de qualquer teste estavam no quintil superior (253 ng/dL, 47 ng/dL e 1,8 mg/dL, respectivamente para cortisol salivar 23:00 h e salivar e sérico pós-DST) foram reavaliados. Os valores médios desse grupo encontravam-se 2,5 vezes acima dos valores dos demais pacientes. Após um teste confirmatório com 2 mg x 2 dias DST, a investigação da SC foi encerrada para 61 pacientes com todos os testes normais e 33 com apenas um teste (falso) positivo. Todos os 8 pacientes com dois testes alterados apresentaram cortisol urinário normal, mas 3 deles mostraram maior probabilidade diagnóstica de SCS (hipercortisolismo e alterações em exames de imagem). Contudo, o diagnóstico final não pode ser confirmado por cirurgia ou patologia em nenhum deles. Embora não confirmatórios, os resultados deste estudo sugerem que a prevalência de SCS seja maior em populações de risco do que na população geral.

Estudio de 34 pacientes con incidentaloma suprarrenal / A study of 34 cases of adrenal incidentaloma

El incidentaloma suprarrenal, un tumor de dicha glándula descubierto por razones independientes de la sospecha de enfermedad adrenal, constituye un problema clínico frecuente. Aunque en la mayoría de los casos son benignos y no hiperfuncionantes, es importante identificar oportunamente la minoría de lesiones malignas o hiperfuncionantes de resolución quirúrgica. Si bien han sido diseñadas distintas estrategias de diagnóstico hay controversia alrededor de una serie de cuestiones. En el presente trabajo retrospectivo once (32%) de nuestros 34 pacientes presentaban masas adrenales hiperfuncionantes manifestadas por síndrome de Cushing subclínico en cuatro, feocromocitoma en tres, probable hiperaldosteronismo primario en dos y por hiperplasia adrenal congénita de origen tardío y carcinoma funcionante en los dos restantes. Las características de las imágenes por TAC y/o RM permitieron identificar los adenomas a la vez que decidir la cirugía tanto en dos pacientes con feocromocitomas bioquímicamente no funcionantes como en una paciente con un carcinoma adrenocortical primitivo, este diagnóstico también sugerido por un patrón mixto de hipersecreción de andrógenos y cortisol. En una paciente con síndrome de Cushing subclínico, hipertensa y diabética, ambas comorbilidades fueron resueltas por la cirugía. Los tumores no funcionantes fueron en su mayoría adenomas (87%), hallándose además histoplasmosis, pseudoquiste, hiperplasia suprarrenal idiopática y mielolipoma. Seis de los ocho pacientes operados tenían enfermedad maligna y/o hiperfuncionante. La condición asociada a los incidentalomas suprarrenales significó un amplio espectro de riesgo para los pacientes y reafirma la necesidad de una minuciosa evaluación clínica, bioquímica y de las imágenes a fin de adoptar conductas adecuadas.

Adrenal incidentaloma, a tumor discovered unexpectedly during imaging performed for non-adrenal related causes, has become a frequent clinical concern. Although in most cases they are benign and hormonally nonfunctioning, it is important to appropriately identify those few cases of malignant or hyperfunctioning lesions of surgical resolution. Although several proposals for an optimal diagnostic strategy have been designed, controversy over a series of questions still persists. In the present retrospective study we analyzed 34 patients with adrenal incidentaloma. Of these, 32% of the patients displayed hyperfunctioning pathologies that included subclinical Cushing's syndrome in four patients, probable primary hyperaldosteronism in two, late onset congenital adrenal hyperplasia in one, adrenocortical carcinoma in one and pheochromocytoma in three. CT and/or MRI permitted the identification of adenomas and were crucial to decide on surgery in two patients with nonfunctioning pheochromocytomas and in a patient carrying a primitive adrenocortical carcinoma, a diagnosis also suggested by a mixed pattern of hypersecretion of androgens and cortisol. In a diabetic and hypertensive patient with subclinical Cushing's syndrome both comorbidities were solved by surgery. Nonfunctioning tumors were mainly adenomas (87%) with individual cases of histoplasmosis, pseudocyst, idiopathic adrenal hyperplasia and mielolipoma. Six of the eight operated patients presented malignant and/or hyperfunctioning tumors. The pathology associated with incidentalomas represents a broad spectrum of risk for patients and reaffirms the necessity for a meticulous clinical, biochemical, and imaging evaluation in order to make appropriate decisions.