Etomidato en el tratamiento del síndrome de Cushing / Etomidate in the treatment of Cushing syndrome

El síndrome de Cushing es una enfermedad metabólica causada por la exposición crónica a niveles elevados de glucocorticoides. Se puede presentar como una emergencia endocrina por un aumento rápido de los niveles de cortisol en sangre, con aumento de la morbimortalidad por enfermedad cardiovascular e infecciones. El etomidato es un fármaco que permite el control rápido de los niveles de cortisol plasmáticos, por inhibición del enzima 11β-hidroxilasa. Presentamos un caso clínico de hipercortisolemia severa, acompañada de alteraciones metabólicas y neuropsiquiátricas, en el que el control de los niveles de cortisol previamente a la cirugía se consiguió con perfusión de etomidato. (AU)

Cushing syndrome is a metabolic disease caused by chronic exposure to high levels of glucocorticoids. It can present as an endocrine emergency due to a rapid increase in circulating cortisol leading to increased risk of cardiovascular disease and infection. Etomidate rapidly reduces plasma cortisol levels by inhibiting the action of 11β-hidroxilase. We report the case of a patient with severe hypercortisolaemia accompanied by metabolic and psychiatric disorders in whom administration of etomidate reduced preoperative levels of cortisol. (AU)

Etomidate in the treatment of Cushing syndrome.

Cushing syndrome is a metabolic disease caused by chronic exposure to high levels of glucocorticoids. It can present as an endocrine emergency due to a rapid increase in circulating cortisol leading to increased risk of cardiovascular disease and infection. Etomidate rapidly reduces plasma cortisol levels by inhibiting the action of 11ß-hidroxilase. We report the case of a patient with severe hypercortisolaemia accompanied by metabolic and psychiatric disorders in whom administration of etomidate reduced preoperative levels of cortisol.

Evaluación del incidentaloma adrenal / Evaluation of the adrenal incidentaloma

An adrenal incidentaloma is a mass detected by chance on an imaging test. It is important that general practitioners know how to manage it, since it is an increasingly frequent finding. It is necessary to assess whether it presents malignant characteristics in imaging tests and the possibility of subclinical hormonal hyperfunction. The basic hormonal study evaluates the overproduction of catecholamines with a study of fractionated metanephrines in plasma or in 24-hour urine, hypercortisolism with a dexamethasone suppression test, and, in patients with hypertension or hypokalemia, the possibility of hyperaldosteronism with determination of the plasma aldosterone/renin ratio. Surgical treatment is indicated in hyperfunctioning nodules, those with suspicion of malignancy or in large ones. (AU)

El incidentaloma adrenal es una masa detectada de forma casual en una prueba de imagen. Es importante que los médicos generalistas conozcan su manejo, ya que es un hallazgo cada vez más frecuente. Hay que valorar si presenta características de malignidad en las pruebas de imagen y la posibilidad de hiperfuncionalidad hormonal subclínica.El estudio hormonal básico evalúa la sobreproducción de catecolaminas con un estudio de metanefrinas fraccionadas en plasma o en orina de 24 horas, el hipercortisolismo con una prueba de frenación con dexametasona y, en pacientes con hipertensión o hipopotasemia, la posibilidad de hiperaldosteronismo con la determinación del cociente aldosterona/renina plasmáticas. El tratamiento quirúrgico está indicado en nódulos hiperfuncionantes, con sospecha de malignidad o en aquellos de gran tamaño. (AU)

Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing's syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing's syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing's syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.

El reto diagnóstico de la enfermedad de Cushing en pediatría: reporte de casos

Introducción: la enfermedad de Cushing (EC) se debe sospechar en el paciente pediátrico con retraso del crecimiento, aumento de peso y fenotipo característico. Se sugiere iniciar el protocolo diagnóstico, que consiste en: comprobación de hipercortisolemia, sitio de producción del cortisol e imágenes, para finalmente realizar el tratamiento quirúrgico curativo. Reporte de casos: se presentan los casos de tres pacientes con alteración de la velocidad de crecimiento, aumento de peso y fenotipo característico. Se realiza la secuencia diagnóstica para demostrar el hipercortisolismo, posteriormente se confirma EC y se realiza imagen por resonancia magnética nuclear (RMN) de hipófisis. Finalmente se lleva a cabo el tratamiento quirúrgico curativo. Conclusiones: la EC en pediatría sigue siendo un desafío diagnóstico. Un abordaje para su detección inicia con la sospecha clínica asociada a una adecuada interpretación de los estudios bioquímicos e imágenes, lo que permite realizar un diagnóstico oportuno y un tratamiento curativo definitivo.

Summary Introduction: Cushing's disease (CD) should always be suspected in a pediatric patient with growth delay, excessive weight gain and characteristic phenotype. It is suggested to start a diagnostic protocol sequence: verification of hypercortisolism, production site and images, to finally perform the definitive curative surgical treatment. Case reports: We report three CD patients with altered growth velocity, weight gain and characteristic phenotype. The diagnostic sequence was performed to demonstrate hypercortisolism. CD was subsequently confirmed, and a pituitary nuclear magnetic resonance (NMR) was performed. All patients underwent curative surgery. Conclusion: CD in pediatrics continues to be a diagnostic challenge for the clinician. An approach with high initial clinical suspicion, associated with paraclinical studies and obtaining the adequate images, are necessary to make an accurate diagnosis and a definitive curative treatment.

Prevalencia y fenotipo de la hiperplasia suprarrenal macronodular bilateral primaria con secreción autónoma de cortisol: un estudio de 98 pacientes / Prevalence and phenotype of primary bilateral macronodular adrenal hyperplasia with autonomous cortisol secretion: a study of 98 patients

Objetivo Se evaluó la prevalencia de hiperplasia suprarrenal macronodular bilateral primaria (PBMAH). También se analizó el fenotipo diferencial de los pacientes con PBMAH en comparación con otras lesiones suprarrenales bilaterales que no cumplían con la definición de PBMAH. Métodos Revisamos las historias clínicas de 732 pacientes diagnosticados de incidentaloma suprarrenal en nuestro centro. Se incluyeron 98 pacientes con hipercortisolismo subclínico para el análisis. Se definió PBMAH como la presencia de cortisol plasmático > 1,8 μg/dL después de una prueba de 1 mg de dexametasona durante la noche, hiperplasia suprarrenal bilateral y nódulos suprarrenales bilaterales > 1 cm. Resultados Un total de 31 pacientes tenían PBMAH. Los pacientes con PBMAH mostraron una mayor prevalencia de secreción autónoma de cortisol (cortisol plasmático > 5,0 μg/dL después de la prueba de 1 mg de dexametasona durante la noche) que los pacientes sin PBMAH (OR 4,1, IC del 95%: 1,38-12,09, p = 0,010). El tamaño del tumor y la masa adenomatosa total fueron significativamente mayores en pacientes con PBMAH en comparación con los pacientes sin PBMAH (30,2 ± 12,16 vs. 24,3 ± 8,47 mm, p = 0,010 y 53,9 ± 20,8 vs. 43,3 ± 14,62 mm, p = 0,023), respectivamente. Una mayor proporción de pacientes con PBMAH tenían diabetes en comparación con los pacientes sin PBMAH (45,2% vs. 25,4%, p = 0,05). Conclusión PBMAH está presente en un tercio de los pacientes con incidentaloma suprarrenal e hipercortisolismo subclínico. Los pacientes con PBMAH mostraron una mayor secreción autónoma de cortisol, mayor tamaño del tumor y diabetes que aquellos sin PBMAH (AU)

Aim This study evaluated prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH). It also analyzed the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions that do not meet the definition of PBMAH. Methods We reviewed the medical records of 732 patients diagnosed with an adrenal incidentaloma at our center. Ninety-eight patients with subclinical hypercortisolism were included in the analysis. We defined PBMAH as the presence of plasma cortisol > 1.8 μg/dL after an over-night 1-mg dexamethasone test, bilateral adrenal hyperplasia, and bilateral adrenal nodules > 1 cm. Results A total of 31 patients had PBMAH. Patients with PBMAH showed greater prevalence of autonomous cortisol secretion (plasma cortisol > 5.0 μg/dL after an overnight 1-mg dexamethasone test) than patients without PBMAH (OR 4.1, 95%CI 1.38-12.09, p = 0.010). Tumor size and total adenomatous mass were significantly greater in patients with PBMAH compared to patients without PBMAH (30.2 ± 12.16 vs. 24.3 ± 8.47 mm, p = 0.010 and 53.9 ± 20.8 vs. 43.3 ± 14.62 mm, p = 0.023), respectively. A greater proportion of patients with PBMAH had diabetes compared to patients without PBMAH (45.2% vs. 25.4%, p = 0.05). Conclusion PBMAH is present in one-third of patients with adrenal incidentaloma and subclinical hypercortisolism. Patients with PBMAH showed greater autonomous cortisol secretion, bigger tumor size, and higher rates of diabetes than those without PBMAH (AU)

Prevalence and phenotype of primary bilateral macronodular adrenal hyperplasia with autonomous cortisol secretion: a study of 98 patients.

AIM: This study evaluated prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH). It also analyzed the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions that do not meet the definition of PBMAH. METHODS: We reviewed the medical records of 732 patients diagnosed with an adrenal incidentaloma at our center. Ninety-eight patients with subclinical hypercortisolism were included in the analysis. We defined PBMAH as the presence of plasma cortisol > 1.8 µg/dL after an over-night 1-mg dexamethasone test, bilateral adrenal hyperplasia, and bilateral adrenal nodules > 1 cm. RESULTS: A total of 31 patients had PBMAH. Patients with PBMAH showed greater prevalence of autonomous cortisol secretion (plasma cortisol > 5.0 µg/dL after an overnight 1-mg dexamethasone test) than patients without PBMAH (OR 4.1, 95%CI 1.38-12.09, p = 0.010). Tumor size and total adenomatous mass were significantly greater in patients with PBMAH compared to patients without PBMAH (30.2 ±â€¯12.16 vs. 24.3 ±â€¯8.47 mm, p = 0.010 and 53.9 ±â€¯20.8 vs. 43.3 ±â€¯14.62 mm, p = 0.023), respectively. A greater proportion of patients with PBMAH had diabetes compared to patients without PBMAH (45.2% vs. 25.4%, p = 0.05). CONCLUSION: PBMAH is present in one-third of patients with adrenal incidentaloma and subclinical hypercortisolism. Patients with PBMAH showed greater autonomous cortisol secretion, bigger tumor size, and higher rates of diabetes than those without PBMAH.

Inferior petrosal sinus sampling and stimulation with CRH: 15 years of experience in a tertiary hospital.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is indicated in the diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), especially when the results of the initial diagnostic tests are discordant. OBJECTIVE: To describe the patients who underwent this invasive functional test in a tertiary hospital. METHODS: This was an observational study of a retrospective cohort of patients with ACTH-dependent CS and IPSS between 2004 and 2019. We determined their epidemiological, hormonal, radiological and functional characteristics, and evaluated their diagnostic capacity and optimal cut-off points to differentiate between Cushing's disease (CD) and ectopic Cushing's syndrome (ECS). RESULTS: 23 patients were evaluated, of which 65.2% were women with the average age of 42 (36-62) years. ACTH secretion of pituitary origin was evident in 82.6% of the patients and of ectopic origin in 17.4%. Plasma cortisol, urinary free cortisol, and ACTH levels were higher in patients with ECS. Regarding IPSS, the baseline central/peripheral ACTH gradient detected 89.5% of patients with CD and after stimulation with CRH, 100%. The optimal cut-off points in the diagnosis of CD were 2.06 at baseline and 2.49 after CRH stimulation. CONCLUSION: IPSS with CRH stimulation is a test with a high diagnostic accuracy for correctly classifying patients with CD and ECS. The cut-off points of the gradients may be different from the classic ones. Therefore, we recommend that each center perform its own evaluation.

Manifestaciones clínicas predictivas del diagnóstico del hipercortisolismo endógeno / Clinical Manifestations Predicting Endogenous Hypercortisolism

Introducción: El diagnóstico clínico del hipercortisolismo endógeno puede ser complejo si las manifestaciones clínicas no son patognomónicas. Es importante conocer cuáles son las distintivas en nuestros pacientes, que permitan diagnosticar la enfermedad de forma precoz. Objetivo: Determinar sensibilidad, especificidad y valor predictivo positivo de las manifestaciones clínicas para diagnosticar el hipercortisolismo endógeno. Métodos: Estudio descriptivo transversal. Grupo I: 65 pacientes con hipercortisolismo endógeno y grupo II (comparación): 75 con sospecha clínica de hipercortisolismo endógeno a los que se les descartó la enfermedad. Se estudiaron pacientes con diagnóstico de hipercortisolismo endógeno (2004-2017), atendidos en el Instituto de Endocrinología. Se determinaron los valores de sensibilidad, especificidad y valor predictivo positivo para el diagnóstico de hipercortisolismo endógeno de cada síntoma y signo por separado, así como para las combinaciones de tres manifestaciones clínicas; además se realizó una regresión logística binaria para identificar las combinaciones de sintomatologías que mejor predicen la presencia de hipercortisolismo endógeno. Se consideró diferencia estadística significativa con p ≤ 0,05. Resultados: La mayoría de los síntomas presentó una sensibilidad inferior al 45 por ciento. La circunferencia de la cintura fue el único signo que mostró alta sensibilidad (76,9 por ciento), baja especificidad (28,6 por ciento) con valor predictivo positivo de 42,0 por ciento. Cuando se presentan dos o tres de estos signos: rubicundez, cara de "luna llena" e hirsutismo la posibilidad de tener hipercortisolismo endógeno es 75,4 por ciento, con valor predictivo positivo de 71 por ciento y, cuando no están presentes la probabilidad de no tenerlo es de 77,5 por ciento. Conclusiones: La combinación de sensibilidad, especificidad y valor predictivo positivo de los síntomas y signos de forma aislada no predice el diagnóstico de la enfermedad; sin embargo, la presencia de dos o tres de los síntomas y/o signos tiene una elevada sensibilidad y valor predictivo positivo para el diagnóstico del hipercortisolismo endógeno. Las combinaciones que mejor predicen la posibilidad de tener un hipercortisolismo endógeno son: piel fina, edema y acné; cara de "luna llena", hirsutismo y rubicundez, así como "giba de búfalo", hematomas y estrías(AU)

ABSTRACT Introduction: The clinical diagnosis of endogenous hypercortisolism can be complex if clinical manifestations are not pathognomonic. It is important to know what are distinctive in our patients, which allows to diagnose the disease early. Objective: To determine the sensitivity, specificity and positive predictive value of clinical manifestations for diagnosis. of endogenous hypercortisolism. Methods: Descriptive and cross-sectional study. Group I was made up of 65 patients with endogenous hypercortisolism; group II (comparison) was made up of 75 patients with clinical suspicion of endogenous hypercortisolism, finally ruled out. We studied patients diagnosed of endogenous hypercortisolism from 2004 to 2017, treated at the Endocrinology Institute. Sensitivity, specificity and positive predictive values were determined for the diagnosis of endogenous hypercortisolism for each symptom and sign separately, as well as for the combinations of three clinical manifestations; in addition, binary logistic regression was performed to identify the combinations of symptoms that best predict the presence of endogenous hypercortisolism. A statistically significant difference was considered with p ≤ 0.05. Results: Most of the symptoms presented a sensitivity lower than 45 percent. Waist circumference was the only sign that showed high sensitivity (76.9 percent), low specificity (28.6 percent), and positive predictive value of 42.0 percent. When two or three of these signs (redness, "full-moon" face, and hirsutism) are present, the possibility of having endogenous hypercortisolism is 75.4 percent, with positive predictive value of 71 percent; and, when they are not present, the probability of not having it is 77,5 percent. Conclusions: The combination of sensitivity, specificity and positive predictive value of the symptoms and signs in isolation does not predict the diagnosis of the disease; however, the presence of two or three of the symptoms and/or signs has a high sensitivity and positive predictive value for the diagnosis of endogenous hypercortisolism. The combinations that best predict the possibility of having an endogenous hypercortisolism are thin skin, edema and acne; "full-moon" face, hirsutism and redness; as well as "buffalo hump," bruises and stretch marks(AU)

Canine endogenous adrenocorticotrophic hormone preanalytical stability after sample shipping in dry ice or recyclable ice bars / Estabilidade pré-analítica do hormônio adrenocorticotrófico endógeno canino após remessa de amostras em gelo seco ou com barras de gelo reciclável

ABSTRACT: Endogenous adrenocorticotrophic hormone (eACTH) measurement is useful in hypercortisolism and hypoadrenocorticism investigation; however, since the hormone is highly unstable, blood samples require proper processing and storage, as well as shipping is often a step limiting since few laboratories offer this assay in Brazil. The aim of this note was to compare overnight dog´s eACTH preanalytical stability when frozen samples were shipped in dry ice (DI), or with recyclable ice bars (RIB). A total of 56 paired samples for eACTH measurement were analyzed. Blood samples were properly handled, plasma aliquots transferred into plastic microtubes, and stored at -80ºC. The fifty-six paired samples were overnight shipped in two thermic isolated boxes with DI or involved by RIB. Despite there was a high correlation between results from both shipping methods (r Spearman = 0.958, P<0.001), the Wilcoxon matched-pairs rank test showed that the shipping method may influence results (P<0.001). However, this difference does not affect results interpretation. By this way, when DI shipping was not possible, RIB shipping may represent a risk to eACTH preanalytical stability.

RESUMO: A mensuração do hormônio adrenocorticotrófico endógeno (ACTHe) é útil na investigação do hipercortisolismo e hipoadrenocorticismo. No entanto, como o hormônio é bastante instável, as amostras de sangue necessitam um manejo adequado no processamento e armazenamento, assim como o envio para laboratórios pode ser um passo limitante, uma vez que poucos laboratórios oferecem este ensaio no Brasil. O objetivo deste trabalho foi comparar a estabilidade pré-analítica do ACTHe durante longo período de envio de amostras congeladas em gelo seco (GS), ou com barras de gelo reciclável (BGR). Um total de 56 amostras pareadas para mensuração de ACTHe foram analisadas. As amostras de sangue foram adequadamente manejadas, sendo o plasma transferido para micro tubos plásticos estocados a -80ºC. Os 56 pares de amostras foram enviados à tarde para chegada ao laboratório na manhã seguinte em dois isopores, um com GS e outro com BGR. Apesar de uma alta correlação entre os resultados dos diferentes métodos de envio (r Spearman = 0,958, P<0,001), o teste de Wilcoxon para amostras pareadas mostrou que o método de envio influencia os resultados P<0,001). Apesar desta diferença, os resultados não afetaram a interpretação dos resultados. Desta forma, quando o envio em gelo seco não for possível, o envio das amostras com barras de gelo reciclável pode representar um risco à estabilidade pré-analítica do ACTHe.

Functional imaging of adrenal cortex. / Estudios de imagen funcional de la corteza adrenal.

The rising number of high-resolution imaging scans has increased the adrenal lesions detection, which require a differential diagnosis. Currently, the most commonly used scans are CT and MRI, but these are sometimes not very specific. In these cases, nuclear medicine scans with 131I-norcolesterol, 11C-metomidate and 18F-fludeoxyglucose help to differentiate benign vs. malignant lesions, to lateralize the involvement in hypersecretion disease, as well as to guide the therapeutic strategy in both unilateral and bilateral lesions.

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014) / Aspectos epidemiológicos, clínicos e laboratoriais em uma série de cães com hiperadrenocorticismo: 115 casos (2010-2014)

Diseases' clinical-epidemiological characterization assists in directing the diagnosis. The objective of this study was to describe epidemiological, clinical and laboratorial aspects of a case series of canine hyperadrenocorticism (HAC). One-hundred fifteen records of dogs diagnosed by the low dose dexamethasone suppression test and/or ACTH stimulation test were evaluated. Of the cases, 81.3% were HAC ACTH-dependent and 18.7% HAC ACTH-independent. Females were more affected, representing 69.3% of the cases. The mean age was 10.3±2.5 years and 64.9% were gonadectomized. Most of the patients were small size dogs, weighting less than 10kg (73.9%). The most frequent breeds were: Poodle (27%), Dachshund (17.4%), and Yorkshire Terrier (10.4%). The most frequent clinical manifestations were polyphagia (86%), polydipsia (82.6%), polyuria (80%), abdominal enlargement (82.6%), thin skin (79.1%), muscular weakness (78.3%) and panting (74.8%). However, eventually unusual HAC-associated signs would be present in some dogs in a more important way compared with the classic disease´s clinical signs. The CBC showed neutrophilia (66%), eosinopenia (58.3%) and lymphopenia (42.6%) as main hematological abnormalities. The most common findings in serum biochemistry were increased alkaline phosphatase activity (81.74%), increased ALT activity (62.6%), hypercholesterolemia (66%) and hypertriglyceridemia (54.7%). Urinalysis revealed hyposthenuria in 14.9% and isostenuria in 13.5%; besides proteinuria in 50% of the cases. Abdominal ultrasound showed bilateral adrenal hyperplasia (92.2%) with adrenal asymmetry in 20.8% of the cases, in addition to hepatomegaly (80.9%), biliary sludge (67.8%) and hepatic hyperechogenicity (47.8%). It was concluded that small size gonadectomized female dogs, mainly Poodles and Dachshunds, presented higher frequency in the population studied, and that the main changes observed in clinical and complementary tests were polyphagia, polyuria, polydipsia, abdominal enlargement, adrenal hyperplasia, increased phosphatase alkaline and hyperlipidemia. These results corroborated to a better disease characterization at Brazil. This work concluded that the population studied resembles the profile describe in European and North American epidemiologic studies, and that the HAC dog´s clinical picture looks similar worldwide.(AU)

A caracterização clínica-epidemiológica de doenças auxilia no direcionamento do diagnóstico. O objetivo deste trabalho foi descrever aspectos epidemiológicos, clínicos e laboratoriais de uma série de casos de hiperadrenocorticismo (HAC) canino. Foram avaliados 115 prontuários de cães diagnosticados pelo teste de supressão por baixa dose de dexametasona e/ou teste de estimulação com ACTH. Os casos de HAC ACTH-dependentes representaram 81,3% da população, e 18,7% foram ACTH-independentes. As fêmeas foram mais acometidas, representando 69,3% dos casos. A média de idade foi 10,3 ± 2,5 anos e 64,9% eram gonadectomizados. A maioria dos cães foi de porte pequeno, de até 10 kg (73,9%). As raças mais frequentes foram Poodle (27%), Dachshund (17,4%) e Yorkshire (10,4%). As manifestações clínicas mais relatadas foram polifagia (86%), polidipsia (82,6%), poliúria (80%), abdome pendular (82,6%), atrofia cutânea (79,1%), fraqueza muscular (78,3%) e dispneia (74,8%). Entretanto, eventualmente sinais clínicos pouco associados ao HAC se manifestaram de forma mais importante que os sinais clássicos da doença. O hemograma revelou neutrofilia (66%), eosinopenia (58,3%) e linfopenia (42,6%) como principais alterações hematológicas. Na bioquímica sérica foi observado aumento de fosfatase alcalina (81,74% dos casos), aumento da atividade da ALT (62,6%), hipercolesterolemia (66%) e hipertrigliceridemia (54,7%). A urinálise revelou hipostenúria em 14,9% e isostenúria em 13,5%; além de proteinúria em 50% dos casos. A ecografia abdominal evidenciou hiperplasia bilateral de adrenal (92,2%) com assimetria de adrenais em 20,8% dos casos, além de hepatomegalia (80,9%), lama biliar (67,8%) e hiperecogenicidade hepática (47,8%). Concluiu-se que fêmeas castradas de pequeno porte, principalmente das raças Poodles e Dachshunds, apresentaram maior frequência na população estudada e que as principais alterações observadas clínicas e nos exames complementares foram polifagia, poliúria, polidipsia, aumento abdominal, hiperplasia da adrenal, aumento de fosfatase alcalina e hiperlipidemia. Estes resultados corroboram para melhor caracterização da doença no Brasil. Este estudo concluiu que a população estudada se assemelha ao perfil populacional de cães com HAC descrito em estudos Europeus e Norte Americanos de forma que o perfil dos casos ao redor do globo parece similar.(AU)

Calidad de vida en pacientes operados de hipercortisolismo endógeno / Quality of life in patients operated for endogenous hypercortisolism

RESUMEN Introducción: El hipercortisolismo endógeno provoca cambios en diferentes áreas de la vida en el sentido percibido de bienestar, lo que afecta la calidad de vida; esta debe tenerse en cuenta en la atención integral al paciente. Objetivos: Describir la calidad de vida percibida en los pacientes con hipercortisolismo endógeno e identificar si existe relación entre calidad de vida y algunas características clínicas y hormonales. Métodos: Estudio transversal, 60 pacientes: grupo I (con hipercortisolismo endógeno operados con menos de cinco años) y grupo II (personas con sospecha clínica de hipercortisolismo endógeno), edad entre 20 y 60 años. Se aplicaron cuestionarios de calidad de vida relacionados con el hipercortisolismo endógeno: CushingQoL y Tuebingen CD-25 y planilla de recolección de datos generales, clínicos y hormonales. Se determinó mediana (variables cuantitativas) y frecuencia en las cualitativas. La asociación del puntaje de los cuestionarios y variables cuantitativas, mediante el coeficiente de correlación de Spearman. Se compararon los valores promedio del puntaje entre categorías de las variables cualitativas (clínicas y hormonales categorizadas), mediante la prueba U-Mann Whitney; se consideró diferencia estadística significativa con p ≤ 0,05. Resultados: La mediana del puntaje de los dominios psicoemocional, sexualidad, área social, área corporal, y la suma de todos los dominios fueron mayores en el grupo I. La sexualidad (4,5), el área corporal (6,0) y la suma de todos los dominios (36,5) del I vs. 1,0, 4,0 y 28,0 respectivamente (grupo II), del Tuebingen CD-25 mostraron diferencias estadísticamente significativas, demostrando peor calidad de vida en el grupo I. Con el CushingQoL la mediana del puntaje del grupo I fue menor que la del II (54,1 vs. 74,0), con diferencias estadísticamente significativas (p = 0,00), lo que evidencia peor calidad de vida para el grupo I. Conclusiones: El hipercortisolismo endógeno incide negativamente en la calidad de vida percibida en el grupo de pacientes operados, especialmente en las áreas social, corporal, cognitiva, sexual, y de la conducta alimentaria(AU)

ABSTRACT Introduction: Endogenous hypercortisolism causes changes in different areas of life and the perceived sense of well-being, which affects the quality of life. This should be taken into account in the patient comprehensive care. Objectives: To describe the quality of life perceived in patients with endogenous hypercortisolism and to identify if there is a relationship between quality of life and some clinical and hormonal characteristics. Methods: Cross-sectional study, 60 patients: group I (with endogenous hypercortisolism operated less than five years) and group II (people with clinical suspicion of endogenous hypercortisolism), age between 20 and 60 years. Quality of life questionnaires related to endogenous hypercortisolism were applied: CushingQoL and Tuebingen CD-25 and general, clinical and hormonal data collection form. Median (quantitative variables) and frequency in the qualitative ones were determined. The association of the score of questionnaires and quantitative variables were obtained by means of the Spearman correlation coefficient. The average score values were compared between categories of qualitative variables (clinical and hormonal categorized), using the U-Mann Whitney test; significant statistical difference was considered with p ≤ 0.05. Results: The median score of the psycho-emotional domains, sexuality, social area, body area, and the sum of all domains were higher in group I. Sexuality (4.5), body area (6.0) and the sum of all domains (36.5) of group I vs. 1.0, 4.0 and 28.0 respectively (group II), of the Tuebingen CD-25 showed statistically significant differences, which is worse quality of life in group I. Using the CushingQoL, the median score of group I showed to be lower than in group II (54.1 vs. 74.0) there are statistically significant differences (p = 0.00), which shows worse quality of life in group I. Conclusions: Endogenous hypercortisolism negatively affects the quality of life perceived in the group of operated patients, especially in the social, bodily, cognitive, sexual areas, and eating behaviour(AU)

Ectopic Cushing syndrome: Report of 9 cases. / Síndrome de Cushing ectópico: descripción de 9 casos.

INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. METHODS: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840µg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended.

Uso de baixa dose de ACTH sintético no teste de estimulação da função adrenal para o diagnóstico e controle do hiperadrenocorticismo canino: avaliação da eficácia diagnóstica / Use of low-dose of synthetic ACTH in the adrenal stimulation test for diagnosis and monitoring of canine hyperadrenocorticism: evaluation of diagnostic efficacy

O teste de estimulação com ACTH é o teste de escolha para realizar o controle dos valores de cortisol endógeno em pacientes sob tratamento para o hiperadrenocorticismo canino, podendo ser utilizado também para diagnosticar a doença. Os protocolos atuais utilizam doses que variam entre 5ug/kg a 250ug/animal por administração intravenosa ou intramuscular. Não se constatam estudos com doses menores que as de 5ug/kg em pacientes portadores de hiperadrenocorticismo. No presente estudo, foi testada a dose de 1ug/kg/IV; comparada à dose consagrada de 5ug/kg/IV, em grupos de animais suspeitos de HAC (HAC Diag), animais portadores de HAC e em tratamento (HAC Control) e animais sadios (Sadios). Na dose de 1ug/kg/IV, os valores basais de cortisol dos Sadios foram iguais à média 2,40ug/dL(+/-1,57ug/dL), dos HAC control foi de média 1,53ug/dL(+/-0,93,ug/dL) e dos HAC diag foi média 3,37ug/dL(+/-1,57ug/dL). Os valores pós-ACTH na dose de 1ug/kg foram de média 11,43ug/dL(+/-2,46ug/dL) para animais sadios, 2,67ug/dL(+/-1,39ug/dL) para o grupo HAC Control e média 16,56ug/dL(+/-7,62ug/dL) para o grupo HAC Diag. Os valores basais de cortisol na dose de 5ug/kg foram 0,89ug/dL(+/-0,23ug/dL) para o grupo HAC Control; média 3,08ug/dL(+/-1,99 ug/dL) para o grupo HAC Diag. Os valores pós-ACTH na dose de 5ug/kg foram de média 3,71ug/dL(+/-1,57ug/dL), para o grupo HAC control e média 22,52ug/dL (+/-8,75ug/dL) para o grupo HAC diag. Analisando-se os resultados obtidos, constatou-se que as doses 1 e 5ug/kg de ACTH sintético não diferem entre si, promovendo o mesmo tipo de variação nos valores de cortisol (ANOVA; p=0,225). Também, que a dose de 1ug/kg de ACTH foi igualmente eficaz na elevação dos níveis de cortisol nos três grupo testados (Sadios, HAC Control e HAC Diag; ANOVA, p<0,05). E, pelo teste de Dunn observamos que o grupo HAC control apresenta Δ-cortisol (delta =diferença entre cortisol após estimulo e o cortisol basal) significativamente menor que o dos grupos diagnóstico (p<0,05) e animais sadios (p<0,05). Concluiu-se que a dose de 1ug/kg de ACTH sintético pode ser utilizada com eficácia para a realização do teste de estimulação com ACTH.(AU)

ACTH stimulation is the gold standard test to monitor levels of endogen control of patients under treatment for canine hyperadrenocorticism and it may also be used to diagnose the disease. Current protocols use doses ranging from 5ug/kg to 250ug per animal by intravenous or intramuscular administration. There are no studies with doses inferior to 5ug/kg in adrenopatic patients. In the present investigation, the dose of 1ug/kg/IV was tested; compared with the recommended dose of d 5ug/kg/IV in groups of dogs under clinical suspicion of HAC (HAC Diag), animals under treatment for HAC (HAC Control) and healthy animals (Healthy). Under the dose of 1ug/kg/IV, average results for baseline cortisol values were equal to 2.40ug/dL(+/- 1.57ug/dL) for healthy, 1.53g/dL(+/-0.93ug/dL) for HAC Control and 3.37ug/dL(+/-1.57ug/dL) for HAC Diag. Post-ACTH values in the dose of 1ug/kg were average 11.43ug/dL(+/-2.46ug/dL) for healthy animals, 2.67ug/dL (+/-1.39ug/dL) for HAC Control and 16.56ug/dL(+/-7.62ug/dL) for HAC Diag group. Basal cortisol values at a dose of 5ug/kg were 0.89ug/dL (+/-0.23ug/dL) Control group for HAC; average 3.08ug/dL (+/-1.99ug/dL) for HAC Diag group. Baseline cortisol under the dose of 5ug/kg were average 3.71ug/dL(+/-1.57ug/dL) for HAC Control and 22.52g/dL(+/-8.75ug/dL) for HAC diag. Based on the present results, it was found that both doses of 1 and 5ug/kg of synthetic ACTH do not differ, providing the same kind of change in cortisol values (ANOVA, p=0.225). Also, the dose of 1ug/kg of ACTH was equally effective in raising levels of cortisol in the three groups tested (Healthy, HAC and HAC Control Diag; ANOVA, p<0.05). Through the Dunn test it was observed that HAC Control presented HAC-Δ cortisol (delta = difference between cortisol after stimulation and basal cortisol) significantly lower than HAC Diag (p<0.05) and healthy animals (p<0.05). Therefore the dose of 1ug/kg of synthetic ACTH can be effectively used to perform the ACTH stimulation test effectively.(AU)

Síndrome de Cushing ACTH Dependiente, secreción ectópica: desarrollo de un caso / ACTH Dependent Cushing Syndrome due to ectopic secretion: report of a case

Se presenta el caso de un paciente varón de 32 años, derivado a nuestro servicio para evaluación de cuadro de 8 meses de evolución caracterizado por edema y rubicundez facial, obesidad central, edema en miembros inferiores e hipertensión arterial, compatible con síndrome de Cushing clínico. Aportaba estudios previos con cortisol séríco 29,8 y 33 µg/dl (determinaciones realizadas con un mes de diferencia), ACTH 72,8 pg/ml, cortisol salival 2,1 µg/dl, cortisol libre urinario (CLU) 993,4 µg/24 hs. Los estudios imagenológicos (ecografía doppler renal, TAC de abdomen y pelvis c/contraste oral y e.v., TAC de cráneo s/contraste y RMI de cráneo c/contraste e.v.) no aportaron datos relevantes. Se confirmó bioquímicamente el síndrome de Cushing dependiente de ACTH: cortisol sérico (8 hs) 34,8 µg/dl, ACTH (8 hs) 72 pg/ml, cortisol libre urinario 828 µg/24 hs. El test de Nugent no mostró freno. El test de Liddle (8 mg oral dexametasona 23 hs) produjo un descenso del cortisol plasmático de solo 21%. La función tiroidea, las gonadotrofinas y la prolactina séricas eran normales. La radiografía de tórax mostró mediastino ensanchado e imagen nodular parahiliar basal derecha; esto se confirmó por TAC. La formación nodular medía 20 x 13mm, era de bordes lisos y aspecto inespecífico. Se exploró quirúrgicamente esta lesión, con diagnóstico intraoperatorio de población linfoide de pequeño tamaño. Se realizó nodulectomía por toracotomía con la sospecha de lesión linfoproliferativa. El diagnóstico anatomopatológico definitivo: tumor neuroendócrino bien diferenciado ...

The case of a male patient aged 32, referred to our service for evaluation of 8-month history of facial redness and edema,central obesity, lower limb edema and arterial hypertension consistent with clinical Cushing syndrome is presented. He hadprevious studies showing serum cortisol 29.8 and 33 mg/dl (determinations performed one month apart), ACTH 72.8 pg/ml, salivary cortisol 2.1 µg/dl, urinary free cortisol (UFC) 993.4 µg/24 h. Imaging studies (renal ultrasound doppler, CTof the abdomen and pelvis with oral and iv contrast, skull CT without contrast and skull RMI with iv contrast) did notprovide relevant data. Serum cortisol (8 hours) 34.8 µg/dl, ACTH (8 h) 72 pg/ml, urinary free cortisol 828 µg/24 h: anACTH-dependent Cushing’s syndrome was biochemically confirmed. Nugent’s test was negative. Overnight Liddle’s test (8mg oral dexamethasone 23 h) resulted in a modest decrease (21%) in plasma cortisol. Thyroid function, serum gonadotropinsand prolactin were normal. The chest radiograph showed widened mediastinum and a right basal parahilar nodularimage; this was confirmed by CT. The nodule measured 20 x 13 mm, it had smooth edges and nonspecific appearance. Thislesion was explored surgically, with intraoperative diagnosis of small lymphoid population. Lumpectomy was performed bythoracotomy The final pathological diagnosis was well-differentiated neuroendocrine tumo...

Riesgo cardiovascular en el síndrome de Cushing / Cardiovascular risk found in Cushing syndrome

El síndrome de Cushing se caracteriza por un estado de hipercortisolismo endógeno, que produce múltiples y variadas alteraciones metabólicas que aumentan el riesgo cardiovascular en la fase activa de la enfermedad y aún después de la curación. La presencia de la obesidad central, la dislipidemia, la hipertensión arterial, la resistencia a la insulina y los trastornos en la tolerancia a la glucosa (componentes del síndrome metabólico), aceleran el proceso de la aterosclerosis sistémica. El exceso de glucocorticoides genera además, un estado protrombótico que se acompaña de disfunción endotelial. Esto se traduce en un mayor riesgo de infarto del miocardio, insuficiencia cardiaca, ictus y eventos tromboembólicos venosos. Se ha estimado un incremento de la mortalidad hasta 4 veces mayor cuando se compara a estos pacientes con la población general, de ahí que pueda considerarse una enfermedad potencialmente letal. Asociado a la necesidad de eliminar la causa del exceso de glucocorticoides, se recomienda la evaluación del riesgo cardiovascular global y el tratamiento intensivo de cada uno de los factores de riesgo durante la fase activa, en el periodo de remisión y luego de la curación. Teniendo en cuenta lo mencionado anteriormente y la importancia del tema, se realiza una actualización de la repercusión cardiovascular del hipercortislismo en los pacientes que lo padecen(AU)

Cushing's syndrome is characterized by endogenous hypercortisolism that causes many different metabolic alterations increasing the cardiovascular risk at the active phase of disease and even after recovery. Central obesity, dyslipidemia, blood hypertension, insulin resistance, and glucose tolerance disorders (components of the metabolic syndrome) accelerate the process of systemic atherosclerosis. Excessive glucocorticoids also generate a prothrombotic condition with endothelial dysfunction. This leads to higher risk of myocardial infarction, heart failure, ictus and vein thromboembolic events. A fourfold increase of mortality has been estimated in these patients when compared to the general population; hence this disease may be considered a lethal one. In addition to the need of eliminating the cause of excessive glucocorticoids, it is recommended to evaluate the global cardiovascular risk and the intensive treatment for each of the risk factors during the active phase, in the remission period and after recovery. Taking into account the above-mentioned and the importance of this topic, an update on the cardiovascular impact of hypercortisolism was presented(AU)

Tratamiento farmacológico del síndrome de Cushing / Drug treatment of Cushing's syndrome

El tratamiento farmacológico, aunque no constituye la primera línea de tratamiento en el hipercortisolimo endógeno, desempeña un importante rol en determinados pacientes con síndrome de Cushing. Diversos fármacos pueden ser utilizados, de forma aislada o combinada. El ketoconazol es una opción útil, económica, con determinada seguridad y eficacia a largo plazo. Se realiza una revisión de los medicamentos con mejores resultados, dosis, eficacia, efectos adversos y perspectivas, teniendo en cuenta ensayos clínicos en los que han sido empleados(AU)

Although the drug treatment is not a first line therapy for endogenous hypercortisolism, it plays a key role in certain patients suffering Cushing's syndrome. Several drugs may be used in isolation or in combination. Ketoconazol is a useful, economic, safe and efficacious option at long term. A review was made of drugs with best results, doses, efficacy, adverse effects and perspectives, taking into account clinical assays in which they have been used(AU)

Tratamiento farmacológico del síndrome de Cushing / Drug treatment of Cushing's syndrome

El tratamiento farmacológico, aunque no constituye la primera línea de tratamiento en el hipercortisolimo endógeno, desempeña un importante rol en determinados pacientes con síndrome de Cushing. Diversos fármacos pueden ser utilizados, de forma aislada o combinada. El ketoconazol es una opción útil, económica, con determinada seguridad y eficacia a largo plazo. Se realiza una revisión de los medicamentos con mejores resultados, dosis, eficacia, efectos adversos y perspectivas, teniendo en cuenta ensayos clínicos en los que han sido empleados(AU)

Although the drug treatment is not a first line therapy for endogenous hypercortisolism, it plays a key role in certain patients suffering Cushing's syndrome. Several drugs may be used in isolation or in combination. Ketoconazol is a useful, economic, safe and efficacious option at long term. A review was made of drugs with best results, doses, efficacy, adverse effects and perspectives, taking into account clinical assays in which they have been used(AU)

Riesgo cardiovascular en el síndrome de Cushing / Cardiovascular risk found in Cushing syndrome

El síndrome de Cushing se caracteriza por un estado de hipercortisolismo endógeno, que produce múltiples y variadas alteraciones metabólicas que aumentan el riesgo cardiovascular en la fase activa de la enfermedad y aún después de la curación. La presencia de la obesidad central, la dislipidemia, la hipertensión arterial, la resistencia a la insulina y los trastornos en la tolerancia a la glucosa (componentes del síndrome metabólico), aceleran el proceso de la aterosclerosis sistémica. El exceso de glucocorticoides genera además, un estado protrombótico que se acompaña de disfunción endotelial. Esto se traduce en un mayor riesgo de infarto del miocardio, insuficiencia cardiaca, ictus y eventos tromboembólicos venosos. Se ha estimado un incremento de la mortalidad hasta 4 veces mayor cuando se compara a estos pacientes con la población general, de ahí que pueda considerarse una enfermedad potencialmente letal. Asociado a la necesidad de eliminar la causa del exceso de glucocorticoides, se recomienda la evaluación del riesgo cardiovascular global y el tratamiento intensivo de cada uno de los factores de riesgo durante la fase activa, en el periodo de remisión y luego de la curación. Teniendo en cuenta lo mencionado anteriormente y la importancia del tema, se realiza una actualización de la repercusión cardiovascular del hipercortislismo en los pacientes que lo padecen(AU)

Cushing's syndrome is characterized by endogenous hypercortisolism that causes many different metabolic alterations increasing the cardiovascular risk at the active phase of disease and even after recovery. Central obesity, dyslipidemia, blood hypertension, insulin resistance, and glucose tolerance disorders (components of the metabolic syndrome) accelerate the process of systemic atherosclerosis. Excessive glucocorticoids also generate a prothrombotic condition with endothelial dysfunction. This leads to higher risk of myocardial infarction, heart failure, ictus and vein thromboembolic events. A fourfold increase of mortality has been estimated in these patients when compared to the general population; hence this disease may be considered a lethal one. In addition to the need of eliminating the cause of excessive glucocorticoids, it is recommended to evaluate the global cardiovascular risk and the intensive treatment for each of the risk factors during the active phase, in the remission period and after recovery. Taking into account the above-mentioned and the importance of this topic, an update on the cardiovascular impact of hypercortisolism was presented(AU)