El reto diagnóstico de la enfermedad de Cushing en pediatría: reporte de casos / The diagnostic challenge of Cushing's disease in pediatrics: cases report

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.

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.

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)

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)

Carcinoma adrenocortical incidental em cão: aspectos clínicos, tomográficos e histopatológicos / Incidental adrenocortical carcinoma in dog: clinical, tomographic and histopathological aspects

Background: Adrenal incidentalomas are masses accidentally discovered during imaging examinations performed whenthere is no suspicion of adrenal disease. Even with a low prevalence, it is important to perform a reliable evaluation observing biological behavior and determining whether the hormonal activity is stimulated. Frequently, these masses are notfunctional, but in some cases, there is increased cortisol activity, and patients with adrenal incidentalomas may presenthyperadrenocorticism. This report aims to describe the clinical, tomographic, and histopathological aspects of a case ofadrenal incidentaloma detected in a routine abdominal ultrasound.Case: An 8-year-old, male, maltese dog with occasional emesis, halitosis, claudication of the left pelvic limb, and previous compensated and untreated cardiomyopathy was treated at the Veterinary Hospital of the Federal University of MatoGrosso (HOVET-UFMT). Physical examination revealed arterial hypertension and claudication, with the positive posteriordrawer test suggesting rupture of the cruciate ligament. The blood count showed no alteration, and the serum biochemistryrevealed a slight increase in the activity of alanine aminotransferase. In order to investigate this increase, an abdominalultrasound was performed. Slight hepatomegaly and a heterogeneous mass of irregular edges were observed with a moderate and difficult-to-delimit vascularization of the adrenal gland. Left knee radiography raised the suspicion of rupture ofthe cranial cruciate ligament due to the cranial displacement of the tibia in relation to the femur. Computed tomographywas performed to define the extent and delimitation of the mass, which was compatible with a tumor of the right adrenalgland characterized by the visualization of an abdominal mass...(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)

Carcinoma adrenocortical incidental em cão: aspectos clínicos, tomográficos e histopatológicos / Incidental adrenocortical carcinoma in dog: clinical, tomographic and histopathological aspects

Background: Adrenal incidentalomas are masses accidentally discovered during imaging examinations performed whenthere is no suspicion of adrenal disease. Even with a low prevalence, it is important to perform a reliable evaluation observing biological behavior and determining whether the hormonal activity is stimulated. Frequently, these masses are notfunctional, but in some cases, there is increased cortisol activity, and patients with adrenal incidentalomas may presenthyperadrenocorticism. This report aims to describe the clinical, tomographic, and histopathological aspects of a case ofadrenal incidentaloma detected in a routine abdominal ultrasound.Case: An 8-year-old, male, maltese dog with occasional emesis, halitosis, claudication of the left pelvic limb, and previous compensated and untreated cardiomyopathy was treated at the Veterinary Hospital of the Federal University of MatoGrosso (HOVET-UFMT). Physical examination revealed arterial hypertension and claudication, with the positive posteriordrawer test suggesting rupture of the cruciate ligament. The blood count showed no alteration, and the serum biochemistryrevealed a slight increase in the activity of alanine aminotransferase. In order to investigate this increase, an abdominalultrasound was performed. Slight hepatomegaly and a heterogeneous mass of irregular edges were observed with a moderate and difficult-to-delimit vascularization of the adrenal gland. Left knee radiography raised the suspicion of rupture ofthe cranial cruciate ligament due to the cranial displacement of the tibia in relation to the femur. Computed tomographywas performed to define the extent and delimitation of the mass, which was compatible with a tumor of the right adrenalgland characterized by the visualization of an abdominal mass...

Epidemiological, clinical, and laboratory aspects in a case series of canine hyperadrenocorticism: 115 cases (2010-2014)

ABSTRACT: 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.

RESUMO: 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.

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 [...](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 [...](AU)

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 Ag/dl (determinaciones realizadas con un mes de diferencia), ACTH 72,8 pg/ml, cortisol salival 2,1 Ag/dl, cortisol libre urinario (CLU) 993,4 Ag/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 Ag/dl, ACTH (8 hs) 72 pg/ml, cortisol libre urinario 828 Ag/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 ... (AU)

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 Ag/dl, urinary free cortisol (UFC) 993.4 Ag/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 Ag/dl, ACTH (8 h) 72 pg/ml, urinary free cortisol 828 Ag/24 h: anACTH-dependent CushingÆs syndrome was biochemically confirmed. NugentÆs test was negative. Overnight LiddleÆs 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...(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...

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)

Determination of cortisol and cortisone in human saliva by a liquid chromatography-tandem mass spectrometry method / Determinação de cortisol e cortisona na saliva por método baseado em cromatografia líquida e espectrometria de massas em tandem

Objective Salivary cortisol measurement plays an important role in the evaluation of adrenal function. Its high correlation with free serum cortisol, the easy of sampling and the limited presence of interfering steroids, generated multiple recent studies of its application, in special in the screening of adrenal hyperfunction. In this paper we present our experience in the development of a high pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for salivary cortisol and cortisone measurement. Materials and methods For this study we used 181 saliva samples from our routine diagnostic laboratory. The HPLC-MS/MS method was based on a Waters Quattro Premier tandem mass spectrometer with an electrospray probe. After derivatization with hydroxylamine transitions monitored included cortisol and cortisone. An in-house radioimmunoassay (RIA) was used for salivary cortisol results comparison. Results Functional sensitivity was 24 ng/dL for cortisol and linearity from 24 to 1929 ng/dL. Saliva cortisol values obtained in the 181 samples presented a median of 52 ng/dL with 5‐95% percentile of 24 and 374 ng/dL. With the RIA the results were 86, 25 and 436 ng/dL, respectively, with values for RIA being significantly higher (P<0.0001) and high correlation (r=0.8312, P<0.0001). Cortisone measured in 159 samples showed a median of 278 ng/dL, with 5‐95% percentile of 100 and 1,133 ng/dL. Correlation with cortisol values was significant (r=0.820, P<0.0001). Conclusion We conclude that the HPLC-MS/MS method compares favorably with the RIA for salivary cortisol measurement, with the additional possibility of concomitant cortisone measurement and the evaluation of 11βHSD2 activity. .

Objetivo A dosagem de cortisol salivar é uma metodologia que vem tendo crescente aceitação no estudo da função adrenocortical. Sua alta correlação com a fração livre sérica, facilidade de coleta e presença limitada de interferentes têm originado múltiplas publicações, em especial no screening de pacientes suspeitos de hiperfunção. Neste trabalho apresentamos nossa experiência no desenvolvimento de metodologia baseada em cromatografia líquida e espectrometria de massas (HPLC-MS/MS) para a medida de cortisol e cortisona salivares. Materiais e métodos Para este estudo utilizamos 181 amostras de saliva de nossa rotina diagnóstica. A metodologia de HPLC-MS/MS baseou-se num espectrômetro de massas Waters Quattro Premier. Após derivatização com hidroxilamina, as transições monitoradas incluíram cortisol e cortisona. Um radioimunoensaio (RIE) in house foi empregado para comparação. Resultados A sensibilidade funcional para cortisol foi de 24 ng/dL, com linearidade entre 24 e 1,929 ng/dL. Os valores de cortisol obtidos nas 181 amostras apresentaram mediana de 52 ng/dL, com percentis 5‐95% de 24 e 374 ng/dL. Com o RIE, os resultados foram 86, 25 e 436 ng/L, respectivamente, com os valores obtidos no RIE significativamente mais elevados (P<0,0001), e alta correlação (r=0,8312, P<0,0001). Cortisona, medida em 159 amostras, mostrou mediana de 278 ng/dL, com percentis 5‐95% entre 100 e 1.133 ng/dL. A correlação com os valores de cortisol foi significativa (r=0,820, P<0,0001). Conclusão Concluímos que o método baseado em HPLC-MS/MS compara-se favoravelmente com o RIE para a medida de cortisol salivar, com a possibilidade adicional da medida concomitante de cortisona e avaliação da atividade da enzima 11βHSD2. .

Adenoma hipofisário em pônei: relato de caso / Pituitary Adenoma on pony: report case / Adenoma Hipofisario en poni: reporte de un caso

A disfunção adeno hipofisária (DAH) é a mais comum endocrinopatia dos equídeos idosos. A presença de adenomas em região correspondente a hipófise pode ser associada a esta disfunção. Apesar de várias descrições desta afecção como doença clínica bem definida, suas características fisiopatológicas impõem a ela inúmeras possíveis interferências ao diagnóstico presuntivo. Relata-se neste artigo um caso de DAH por adenoma hipofisário em pônei idoso que apresentava diversos sinais associados a infecções secundárias, comumente predispostas pela endocrinopatia, definindo condição clínica diferenciada. Em função de sua senilidade e de seu estado geral debilitado não houve tempo hábil para diagnóstico in vivo sendo sua condição esclarecida somente em exame post-mortem.(AU)

The Adenohypophyseal dysfunction (AHD) is the most common endocrine disease of older horses.The presence of adenomas in pituitary corresponding region can be commonly associated with this disorder. Despite several descriptions of this condition as well-defined clinical disease, its pathophysiological characteristics impose numerous possible interference to the presumptive diagnosis. It's reported in this paper a case of AHD for pituitary adenomas in older pony that showed several signs associated with secondary infections, commonly . predisposed by endocrinopathy, defining distinct clinical condition. Because of their senility and its weakenedgeneral condition there wasn't enough time for in vivo diagnosis and their condition was only clarified in post mortem exam.(AU)

La disfunción adenohipofisarias (DAH) es Ia enfermedad endocrina más común de los caballos másviejos. La presencia de adenomas en Ia región correspondiente de hipófisis pueden ser comúnmente asociadoscon este trastorno. A pesar de varias descripciones de esta condición como uma enfermedad clínica bien definida,su características fisiopatológicas imponen numerosas posibles interferencias en diagnóstico presuntivo. Se informaen este trabajo un caso de DAH debido a adenomas hipofisarios en poni ancianos que mostraban varios signos asociados a infecciones secundarias, comúnmente predispuestos por endo crinopatía, que definen una condición clínica distinta. Debido a su senilidad y su estado general de debilidad no hubo tiempo suficiente para el diagnóstico in vivo y su condición aclaró sólo en examen post- mortem. (AU)

Adenoma hipofisário em pônei: relato de caso / Pituitary Adenoma on pony: report case / Adenoma Hipofisario en poni: reporte de un caso

A disfunção adeno hipofisária (DAH) é a mais comum endocrinopatia dos equídeos idosos. A presença de adenomas em região correspondente a hipófise pode ser associada a esta disfunção. Apesar de várias descrições desta afecção como doença clínica bem definida, suas características fisiopatológicas impõem a ela inúmeras possíveis interferências ao diagnóstico presuntivo. Relata-se neste artigo um caso de DAH por adenoma hipofisário em pônei idoso que apresentava diversos sinais associados a infecções secundárias, comumente predispostas pela endocrinopatia, definindo condição clínica diferenciada. Em função de sua senilidade e de seu estado geral debilitado não houve tempo hábil para diagnóstico in vivo sendo sua condição esclarecida somente em exame post-mortem.

The Adenohypophyseal dysfunction (AHD) is the most common endocrine disease of older horses.The presence of adenomas in pituitary corresponding region can be commonly associated with this disorder. Despite several descriptions of this condition as well-defined clinical disease, its pathophysiological characteristics impose numerous possible interference to the presumptive diagnosis. It's reported in this paper a case of AHD for pituitary adenomas in older pony that showed several signs associated with secondary infections, commonly . predisposed by endocrinopathy, defining distinct clinical condition. Because of their senility and its weakenedgeneral condition there wasn't enough time for in vivo diagnosis and their condition was only clarified in post mortem exam.

La disfunción adenohipofisarias (DAH) es Ia enfermedad endocrina más común de los caballos másviejos. La presencia de adenomas en Ia región correspondiente de hipófisis pueden ser comúnmente asociadoscon este trastorno. A pesar de varias descripciones de esta condición como uma enfermedad clínica bien definida,su características fisiopatológicas imponen numerosas posibles interferencias en diagnóstico presuntivo. Se informaen este trabajo un caso de DAH debido a adenomas hipofisarios en poni ancianos que mostraban varios signos asociados a infecciones secundarias, comúnmente predispuestos por endo crinopatía, que definen una condición clínica distinta. Debido a su senilidad y su estado general de debilidad no hubo tiempo suficiente para el diagnóstico in vivo y su condición aclaró sólo en examen post- mortem.

Carcinoma adrenal de rápida evolución / Rapidly evolving adrenal carcinoma

Introducción: el carcinoma suprarrenal primario es un tumor poco frecuente, altamente agresivo, de crecimiento rápido, con mayor incidencia entre los 40 y 60 años de edad. Los carcinomas funcionantes representan hasta un 79 por ciento de los tumores corticales, más frecuentes en el sexo femenino, y de estos el 50 por ciento se manifiestan clínicamente como un síndrome de Cushing. La extensión del tumor a estructuras vecinas es común y empeora el pronóstico. La supervivencia media es de 2 años desde el diagnóstico, en particular, cuando existen metástasis en hígado y pulmón. Objetivo: describir las características clínicas, los procederes diagnósticos y terapéuticos de una paciente con carcinoma adrenal de rápida evolución. Presentación del caso: paciente LRS, femenina, blanca, de 49 años de edad, con antecedentes de hipertensión arterial y diabetes mellitus tipo 2, que asiste a consulta por descontrol metabólico y de la hipertensión arterial. Al examen físico, se constatan signos sugestivos de hipercortisolismo, sintomatología que a los 2 meses se acentuó notablemente. Se realizaron estudios basales, dinámicos, imagenológicos y anatomopatológicos, que corroboraron el diagnóstico presuntivo. Se realiza adrenalectomía izquierda con adenectomía regional, y se confirma por anatomía patológica el diagnóstico de carcinoma suprarrenal izquierdo. A los pocos meses de la intervención la paciente fallece con metástasis óseas en columna vertebral. Conclusiones: el reconocimiento temprano de los síntomas y signos de hiperfunción adrenal es muy importante para el diagnóstico y tratamiento oportuno del carcinoma adrenal(AU)

Introduction: primary suprarrenal carcinoma is a highly aggressive rare carcinoma of rapid growth, with greater incidence in 40-60 years age group. The functioning carcinomas represent up to 79 percent of cortical tumors that are more frequent in females, and 50 percent of them clinically manifests as Cushing syndrome. The extension of the tumor to neighboring structures is common and worsens the prognosis. Mean survival rate is 2 years from the time of diagnosis, particularly when there are liver and lung metastases. Objective: to describe the clinical characteristics, the diagnostic and therapeutic procedures in a female patient with rapidly evolving adrenal carcinoma. Case presentation: a patient LRS, female, Caucasian, 49 years-old, with a history of blood hypertension and type 2 diabetes mellitus, who went to the hospital because of lack of metabolic control and blood hypertension. On physical examination, there were observed some signs suggestive of hypercortisolism, symptomatology that became notably acute two months later. Basal, dynamic, imaging and anatomopathological studies were made to corroborate the presumptive diagnosis. Left adrenalectomy with regional adenectomy was performed, and the diagnosis of left suprarenal carcinoma was confirmed through pathological anatomy. Few months later, the patient died from osseous metastasis in her spinal cord. Conclusions: early recognition of symptoms and signs of adrenal hyperfunction is very important for diagnosis and timely treatment of adrenal carcinoma(AU)

Enfermedad de Cushing en un adulto mayor / Cushing's disease in the elderly patient

Introducción: la enfermedad de Cushing se presenta por secreción aumentada de ACTH, debido a tumor hipofisario que estimula la zona fascicular de la corteza suprarrenal y produce hipersecreción de glucocorticoides. Objetivos: explicar manifestaciones clínico-humorales y causales de la enfermedad de Cushing en un adulto mayor. Material y método:estudio descriptivo, retrospectivo. Presentamos paciente de 62 años que ingresa en nuestro centro por manifestaciones de plétora facial, obesidad centrípeta, debuta con hipertensión arterial y diabetes mellitus. Examen físico: datos referidos anteriormente. Programa de estudio: cortisol basal 690 nmol/L. Ritmo circadiano para el cortisol: basal 8:00 am 900 nmol/L y 11.00 pm 754 nmol/L. Inhibiciones con 2mg y 8mg de dexametasona 468 nmo/L y 429 nmol/L respectivamente. Tomografía contrastada de silla turca: aumento del diámetro de la silla turca que no confirma aumento de la glándula, realizar siguiente estudio. Resonancia magnética nuclear de silla turca: tumor intraselar en relación con macroadenoma. Resultado: macroadenoma con secreción aumentada de ACTH. Conclusiones: Enfermedad de Cushing.

Introduction: Cushing's disease arises from increased ACTH secretion from a pituitary tumor that stimulates the area fasciculata of the adrenal cortex and produces hypersecretion of glucocorticoids. Objectives: To explain the clinical and humoral manifestations of Cushing's disease in elderly adults. Methods: The article is a descriptive and retrospective study of a case report on a 62 year old patient that is admitted to our Center with manifestations of facial plethora and centripetal obesity. Onset was characterized by hypertension and diabetes mellitus. Definitive diagnosis was Cushing's disease from a macroadenoma with increased ACTH secretion.