RESUMO
Objective: To evaluate the cumulative incidence, risk factors, and outcomes of COVID-19 in patients with Cushing's disease (CD). Subjects and methods: In all, 60 patients with CD following up in our outpatient clinic answered via phone interview a questionnaire about the occurrence of COVID-19 infection documented by RT-PCR (including the diagnosis date and clinical outcome) and vaccination status. Clinical and biochemical data on disease activity (hypercortisolism) and comorbidities (obesity, diabetes mellitus, and hypertension) were obtained from the patients' electronic medical records. Risk ratios (RRs) of risk factors were obtained using univariate and multivariate analyses. Results: The cumulative incidence of COVID-19 in patients with CD during the observation period was 31.7%, which was higher than that in the general reference population (9.5%). The cumulative incidence of COVID-19 was significantly higher in patients with hypercortisolism (57% versus 17% in those without hypercortisolism, p = 0.012) and obesity (54% versus 9% in those without obesity, p < 0.001) but not in patients with hypertension or diabetes mellitus. On multivariate analysis, hypercortisolism and obesity were each independent risk factors for COVID-19 (RR 2.18, 95% CI 1.06-4.46, p = 0.033 and RR 5.19, 95% CI 1.61-16.74, p = 0.006, respectively). Conclusion: The incidence of COVID-19 in patients with CD was associated with hypercortisolism, as expected, and obesity, a novel and unexpected finding. Thus, correction of hypercortisolism and obesity should be implemented in patients with CD during the current and future COVID-19 outbreaks.
Assuntos
COVID-19 , Síndrome de Cushing , Diabetes Mellitus , Hipertensão , Hipersecreção Hipofisária de ACTH , Humanos , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/epidemiologia , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , COVID-19/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologiaRESUMO
Objective: Germline ARMC5 mutations are considered to be the main genetic cause of primary macronodular adrenal hyperplasia (PMAH). PMAH is associated with high variability of cortisol secretion caused from subclinical hypercortisolism to overt Cushing's syndrome (CS), in general due to bilateral adrenal nodules and rarely could also be due to non-synchronic unilateral adrenal nodules. The frequency of adrenal incidentalomas (AI) associated with PMAH is unknown. This study evaluated germline allelic variants of ARMC5 in patients with bilateral and unilateral AI and in patients with overt CS associated with bilateral adrenal nodules. Methods: We performed a retrospective multicenter study involving 123 patients with AI (64 bilateral; 59 unilateral). We also analyzed 20 patients with ACTH pituitary independent overt CS associated with bilateral adrenal nodules. All patients underwent germline genotyping analysis of ARMC5; abdominal CT and were classified as normal, possible or autonomous cortisol secretion, according to the low doses of dexamethasone suppression test. Results: We identified only one pathogenic allelic variant among the patients with bilateral AI. We did not identify any pathogenic allelic variants of ARMC5 in patients with unilateral AI. Thirteen out of 20 patients (65%) with overt CS and bilateral adrenal nodules were carriers of pathogenic germline ARMC5 allelic variants, all previously described. The germline ARMC5 mutation was observed in only one patient with bilateral AI; it was associated with autonomous cortisol secretion and showed to be a familial form. Conclusion: The rarity of germline ARMC5 mutations in AI points to other molecular mechanisms involved in this common adrenal disorder and should be investigated. In contrast, patients with overt Cushing's syndrome and bilateral adrenal nodules had the presence of ARMC5 mutations that were with high prevalence and similar to the literature. Therefore, we recommend the genetic analysis of ARMC5 for patients with established Cushing's syndrome and bilateral adrenal nodules rather than patients with unilateral AI.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Proteínas do Domínio Armadillo/genética , Síndrome de Cushing/genética , Polimorfismo de Nucleotídeo Único , Doenças das Glândulas Suprarrenais/epidemiologia , Doenças das Glândulas Suprarrenais/etiologia , Doenças das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Alelos , Estudos de Casos e Controles , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Mycobacterium abscessus is a fast-growing non-tuberculous mycobacterium that causes lung, skin, disseminated and other infections, mainly in patients with comorbidities. The diagnosis is based on the identification of the mycobacterium by culture media or molecular tests. Treatment with macrolides and amikacin remains the optimal choice, although it depends on the location and severity of the infection; however, resistance genes have been identified in some subspecies that limit antibiotic efficacy. We present the case of a patient with cutaneous coinfection by Mycobacterium abscessus and Mycobacterium tuberculosis, who presented exogenous Cushing syndrome, a predisposing factor for these infections. In addition, hydatidosis and pulmonary aspergillosis were identified. The patient's anti-tuberculosis treatment was adjusted to manage both mycobacteria, resulting in a favorable evolution.
Mycobacterium abscessus es una micobacteria no tuberculosa de crecimiento rápido, que produce infección pulmonar, cutánea, diseminada y otras, sobre todo en pacientes con comorbilidades. El diagnóstico se basa en la identificación de la micobacteria por medios de cultivo o por pruebas moleculares. El tratamiento con macrólidos y amikacina continúa siendo el ideal, aunque depende de la localización y de la gravedad de la infección, sin embargo, se han identificado genes de resistencia en algunas subespecies que limitan la eficacia antibiótica. Presentamos el caso de un paciente con coinfección cutánea por Mycobacterium abscessus y Mycobacterium tuberculosis, quien presenta un síndrome de Cushing exógeno, factor predisponente para estas infecciones. Además, se identificaron hidatidosis y aspergilosis pulmonares. El tratamiento antituberculoso del paciente se ajustó para manejar ambas micobacterias, y su evolución fue favorable.
Assuntos
Síndrome de Cushing , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium tuberculosis , Tuberculose , Antituberculosos/uso terapêutico , Coinfecção , Comorbidade , Síndrome de Cushing/epidemiologia , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium abscessus/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologiaRESUMO
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)
Assuntos
Animais , Cães , Hiperfunção Adrenocortical/veterinária , Hiperfunção Adrenocortical/epidemiologia , Síndrome de Cushing/veterinária , Síndrome de Cushing/epidemiologiaRESUMO
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)
Assuntos
Animais , Cães , Hiperfunção Adrenocortical/veterinária , Hiperfunção Adrenocortical/epidemiologia , Síndrome de Cushing/veterinária , Síndrome de Cushing/epidemiologiaRESUMO
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)
Assuntos
Humanos , Qualidade de Vida , Coleta de Dados/métodos , Inquéritos e Questionários , Síndrome de Cushing/epidemiologia , Epidemiologia Descritiva , Estudos TransversaisRESUMO
CONTEXT: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning adrenal macronodules and increased cortisol production. Familial clustering of PMAH has been described, suggesting an inherited genetic cause for this condition. OBJECTIVE: The aim of the present study was to identify the gene responsible for familial PMAH. PATIENTS AND METHODS: Forty-seven individuals of a Brazilian family with PMAH were evaluated. A single-nucleotide polymorphism-based genome-wide linkage analysis followed by whole-exome sequencing were then performed in selected family members. Additionally, 29 other patients with PMAH and 125 randomly selected healthy individuals were studied to validate the genetic findings. Moreover, PMAH tissue was also analyzed through whole-exome sequencing, conventional sequencing, and microsatellite analysis. RESULTS: A heterozygous germline variant in the ARMC5 gene (p.Leu365Pro) was identified by whole-exome sequencing in a candidate genomic region (16p11.2). Subsequently, the same variant was confirmed by conventional sequencing in all 16 affected family members. The variant was predicted to be damaging by in silico methods and was not found in available online databases or in the 125 selected healthy individuals. Seven additional ARMC5 variants were subsequently identified in 5 of 21 patients with apparently sporadic PMAH and in 2 of 3 families with the disease. Further molecular analysis identified a somatic mutational event in 4 patients whose adrenal tissue was available. CONCLUSIONS: Inherited autosomal dominant mutations in the ARMC5 gene are a frequent cause of PMAH. Biallelic inactivation of ARMC5 is consistent with its role as a potential tumor suppressor gene.
Assuntos
Síndrome de Cushing/genética , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas do Domínio Armadillo , Brasil , Síndrome de Cushing/epidemiologia , Feminino , Frequência do Gene , Ligação Genética , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
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)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias do Córtex Suprarrenal/diagnóstico , Carcinoma Adrenocortical/epidemiologia , Adrenalectomia/métodos , Síndrome de Cushing/epidemiologia , Metástase Neoplásica/patologiaRESUMO
OBJECTIVES: Successful surgery does not always resolve all the clinical consequences of hypercortisolism in patients with Cushing's disease (CD). Our purpose was to integrally evaluate a group of CD patients cured by pituitary surgery and look for the persistence of CD symptoms, signs, and comorbidities. METHODS: We performed clinical and biochemical evaluations of 29 CD patients (2 males) cured by pituitary surgery. All patients underwent early (median 12 months) and late (median 58 months) postoperative evaluations. We sought information regarding hypercortisolism-related symptoms and signs, as well as metabolic, cardiovascular, reproductive, and psychologic comorbidities. RESULTS: The prevalence of obesity dropped from 72.4% at diagnosis to 31% at early evaluation but increased again to 44.8% at the late evaluation. Diabetes was present in 14 patients (48.3%) at diagnosis and persisted in 9 at the late evaluation. Hypertriglyceridemia was present in 58.6% and 55.1% of patients at diagnosis and at the late follow-up, respectively. The prevalence of hypercholesterolemia was 79.3% at diagnosis, decreased to 55.1% at the early evaluation, and increased to 65.5% at the late evaluation. Menstrual abnormalities were originally present in 15 of 20 women, and 8 of the 15 had recovered normal periods when seen at the last evaluation. Among the 24 patients with depression at diagnosis, 11 and 6 still exhibited mood abnormalities at the early and late evaluations, respectively. CONCLUSIONS: In a variable proportion of patients, the cardiovascular, metabolic, and emotional comorbidities of CD persist after long-term remission, irrespective of the initial degree of hypercortisolism.
Assuntos
Síndrome de Cushing/cirurgia , Depressão/epidemiologia , Fadiga/epidemiologia , Hirsutismo/prevenção & controle , Hipertensão/prevenção & controle , Hipófise/cirurgia , Acne Vulgar/epidemiologia , Acne Vulgar/prevenção & controle , Adolescente , Adulto , Estudos de Coortes , Comorbidade , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/metabolismo , Síndrome de Cushing/fisiopatologia , Depressão/prevenção & controle , Fadiga/prevenção & controle , Feminino , Seguimentos , Hirsutismo/epidemiologia , Hirsutismo/etiologia , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Hidrocortisona/urina , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipopotassemia/epidemiologia , Hipopotassemia/prevenção & controle , Masculino , Distúrbios Menstruais/epidemiologia , Distúrbios Menstruais/etiologia , Distúrbios Menstruais/prevenção & controle , México/epidemiologia , Pessoa de Meia-Idade , Hipófise/metabolismo , Prevalência , Adulto JovemRESUMO
Se presenta el caso de una mujer de 47 años con cuadro clínico de siete meses de evolución caracterizado por aumento progresivo de peso, hipertensión arterial y diabetes mellitus de reciente aparición, hirsutismo facial y en tórax, alopecia frontal, alteraciones en la menstruación e hipopotasiemia. Se consideró el diagnóstico de síndrome de Cushing, por lo cual se iniciaron estudios e extensión para establecer su etiología. Durante su hospitalización presentó una evolución tórpida y falleció. En la autopsia clínica se encontró un carcinoma de la glándula suprarrenal izquierda, de 400 g, aproximadamente, con metástasis a hígado y trombosis masiva de la vena cava, lo que finalmente produjo su muerte.
A 47-year-old woman with a seven-month history of increasing weight, hypertension and recently diagnosed diabetes presented features of hirsutism, frontal baldness, amenorrhea and hypokalemia. These characteristics were considered diagnostic of Cushing´s syndrome, and studies were initialized to identify its etiology. During hospitalization, the patient presented a torpid evolution resulting in death. Clinical autopsy revealed a 400 g carcinoma in the left adrenal gland, liver metastasis and a massive vena cava tumor thrombus which was the final cause of death.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Córtex Suprarrenal/complicações , Carcinoma/secundário , Síndrome de Cushing/etiologia , Neoplasias Hepáticas/secundário , Veia Cava Inferior , Trombose Venosa/etiologia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Baixo Débito Cardíaco/etiologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Diagnóstico Tardio , Progressão da Doença , Evolução Fatal , Neoplasias Hepáticas/complicações , Avaliação de SintomasRESUMO
BACKGROUND: Subclinical hypercortisolism is a secondary cause of hypertension that had never been evaluated in resistant hypertensive patients, a subgroup of general hypertensive individuals with an expected high prevalence of secondary hypertension. METHODS: Four hundred and twenty-three patients with resistant hypertension and ages up to 80 years were screened for the presence of subclinical hypercortisolism by morning serum cortisol after a midnight 1 mg dexamethasone suppression test (DST). Those with morning cortisol of at least 50â nmol/l had hypercortisolism confirmed by two salivary cortisol of at least 3.6 ânmol/l collected at 2300â h. Statistical analysis included bivariate tests between those with positive and negative screening test and with and without confirmed hypercortisolism, and logistic regressions to assess their independent correlates. RESULTS: One hundred and twelve patients (prevalence 26.5%, 95% confidence interval 22.0-31.9%) had the screening test positive for suspected hypercortisolism. None had overt Cushing syndrome. Patients with positive screening were older, more frequently males, had higher prevalences of diabetes and target-organ damage and higher nighttime SBPs than patients with normal screening test results. Thirty-four patients (total prevalence 8.0%, 95% confidence interval: 5.7-11.2%) had confirmed hypercortisolism. Independent correlates of a positive DST were older age (Pâ=â0.007), male sex (Pâ=â0.012) and presence of cardiovascular diseases (Pâ=â0.002) and chronic kidney disease (Pâ=â0.016). Correlates of confirmed subclinical hypercortisolism were older age (Pâ=â0.020), diabetes (Pâ=â0.06) and a nondipping pattern on ambulatory blood pressure monitoring (Pâ=â0.04). CONCLUSION: Patients with resistant hypertension had a relatively high prevalence of subclinical hypercortisolism, and its presence is associated with several markers of worse cardiovascular prognosis.
Assuntos
Síndrome de Cushing/sangue , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Hipertensão/complicações , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Dexametasona/farmacologia , Feminino , Humanos , Hidrocortisona/sangue , Hipertensão/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Modelos Estatísticos , Prevalência , PrognósticoRESUMO
A 47-year-old woman with a seven-month history of increasing weight, hypertension and recently diagnosed diabetes presented features of hirsutism, frontal baldness, amenorrhea and hypokalemia. These characteristics were considered diagnostic of Cushing´s syndrome, and studies were initialized to identify its etiology. During hospitalization, the patient presented a torpid evolution resulting in death. Clinical autopsy revealed a 400 g carcinoma in the left adrenal gland, liver metastasis and a massive vena cava tumor thrombus which was the final cause of death.
Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Carcinoma/secundário , Síndrome de Cushing/etiologia , Neoplasias Hepáticas/secundário , Veia Cava Inferior , Trombose Venosa/etiologia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Baixo Débito Cardíaco/etiologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Diagnóstico Tardio , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/complicações , Pessoa de Meia-Idade , Avaliação de SintomasRESUMO
OBJECTIVES: The aim of this study was to examine the frequency of Cushing's syndrome (CS) in obese patients devoid of specific clinical symptoms of Cushing's syndrome. METHODS: A total of 150 obese patients (129 female, 21 male; mean age 44.41 +/- 13.34 yr; mean BMI 35.76 +/- 7.13) were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC). An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 microg/24 h were considered to be abnormal. Suppression of serum cortisol <1.8 microg/dL after administration of 1 mg dexamethasone was the cut-off point for normal suppression. The suppression of the serum cortisol levels failed in all of the patients. RESULTS: MEASURED LABORATORY VALUES WERE AS FOLLOWS: ACTH, median level 28 pg/ml, interquartile range (IQR) 14-59 pg/ml; fasting glucose, 100 (91-113) mg/dL; insulin, 15.7 (7.57-24.45) mU/ml; fT(4), 1.17 (1.05-1.4) ng/dL; TSH, 1.70 (0.91-2.90) mIU/L; total cholesterol, 209 (170.5-250) mg/dL; LDL-c, 136 (97.7-163) mg/dL; HDL-c, 44 (37.25-50.75) mg/dL; VLDL-c, 24 (17-36) mg/dL; triglycerides, 120.5 (86-165) mg/dL. The median UFC level of the patients was 30 microg/24 h (IQR 16-103). High levels of UFC (>100 microg/24 h) were recorded in 37 patients (24%). Cushing's syndrome was diagnosed in 14 of the 150 patients (9.33%). Etiologic reasons for Cushing's syndrome were pituitary microadenoma (9 patients), adrenocortical adenoma (3 patients), and adrenocortical carcinoma (1 patient). CONCLUSION: A significant proportion (9.33%) of patients with simple obesity were found to have Cushing's syndrome. These findings argue that obese patients should be routinely screened for Cushing's syndrome.
Assuntos
Síndrome de Cushing/diagnóstico , Obesidade/complicações , Adulto , Biomarcadores/urina , Brasil/epidemiologia , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/etiologia , Dexametasona/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/urina , Masculino , Obesidade/urina , Valores de ReferênciaRESUMO
Objectives: The aim of this study was to examine the frequency of Cushing's syndrome (CS) in obese patients devoid of specific clinical symptoms of Cushing's syndrome. Methods: A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13) were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC). An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 ìg/24 h were considered to be abnormal. Suppression of serum cortisol <1.8 ìg/dL after administration of 1 mg dexamethasone was the cut-off point for normal suppression. The suppression of the serum cortisol levels failed in all of the patients. Results: Measured laboratory values were as follows: ACTH, median level 28 pg/ml, interquartile range (IQR) 14-59 pg/ml; fasting glucose, 100 (91-113) mg/dL; insulin, 15.7 (7.57-24.45) mU/ml; fT4, 1.17 (1.05-1.4) ng/dL; TSH, 1.70 (0.91-2.90) mIU/L; total cholesterol, 209 (170.5-250) mg/dL; LDL-c, 136 (97.7-163) mg/dL; HDL-c, 44 (37.25-50.75) mg/dL; VLDL-c, 24 (17-36) mg/dL; triglycerides, 120.5 (86-165) mg/dL. The median UFC level of the patients was 30 ìg/24 h (IQR 16-103). High levels of UFC (>100 ìg/24 h) were recorded in 37 patients (24 percent). Cushing's syndrome was diagnosed in 14 of the 150 patients (9.33 percent). Etiologic reasons for Cushing's syndrome were pituitary microadenoma (9 patients), adrenocortical adenoma (3 patients), and adrenocortical carcinoma (1 patient). Conclusion: A significant proportion (9.33 percent) of patients with simple obesity were found to have Cushing's syndrome. These findings argue that obese patients should be routinely screened for Cushing's syndrome.
Assuntos
Adulto , Feminino , Humanos , Masculino , Síndrome de Cushing/diagnóstico , Obesidade/complicações , Biomarcadores/urina , Brasil/epidemiologia , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/etiologia , Dexametasona/administração & dosagem , Dexametasona , Glucocorticoides/administração & dosagem , Glucocorticoides , Hidrocortisona/urina , Obesidade/urina , Valores de ReferênciaRESUMO
The empty sella turcica is defined as the extension of the subarachnoid space toward the intrasellar region with displacement of the pituitary towards the posteroinferior wall. By autopsy studies, the incidence in the general population is around 20%. The association of Cushing's disease (CD) and empty sella has been infrequently reported. In our group, from a total of 68 patients with CD studied by magnetic resonance imaging (MRI), we found the presence of a primary empty sella syndrome (ESS) in 11 (16%). Of these, 9 had partial and 2 total ESS, and in four of them a microadenoma could be identified. Remission, ascertained by subnormal postoperative cortisol levels in blood and/or urine was obtained in 5 of 6 patients operated on by the transphenoidal route. Following surgery, 2 patients presented cerebrospinal fluid (CSF) leakage, 2 diabetes insipidus, and 2 some form of hypopituitarism, figures apparently higher than in non-ESS patients with CD. Ketoconazole was indicated as second line treatment in 2 patients and as primary therapy in 4, resulting in normal urinary free cortisol (UFC) values, with no complications. The relationship of ESS and CD is probably fortuitous given that the frequency of ESS in the general population is similar. Although in empty sella both surgery and radiotherapy seem to have greater risk of complications, surgery remains the first line treatment. Nevertheless, chronic treatment with ketoconazole could be a useful first choice, particularly when no adenoma is seen, or in those who have contraindications for surgery.
Assuntos
Síndrome de Cushing/epidemiologia , Síndrome da Sela Vazia/epidemiologia , Adulto , Idoso , Síndrome de Cushing/patologia , Síndrome de Cushing/cirurgia , Síndrome da Sela Vazia/patologia , Síndrome da Sela Vazia/cirurgia , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Entre 1982 y 1995, nuestra unidad operó 42 pacientes con patología suprarrenal.Fueron 13 portadores de Enfermedad de Cushing, 11 con feocromocitomas, 6 con adenomas funcionantes, 5 neoplasias malignas, 5 tumores incidentales y 2 casos misceláneos. La vía de abordaje fue transperitoneal. Se efectuaron 14 adrenalectomías bilaterales y 27 unilaterales, incluidas 3 ampliadas por cáncer. La tasa de complicaciones postoperatorias fue de 20 por ciento, básicamente respiratorias. Un caso reoperado por hemoperitoneo, y 1 fallecido (2 por ciento). Otros 4 casos de cáncer suprarrenal fallecen dentro de 24 meses. Se mantienen en control actualmente, 33 de los 37 pacientes restantes, con sobrevida entre 2 y 13 años. La vía de abordaje abdominal es conveniente para el manejo de estas lesiones
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adrenalectomia , Doenças das Glândulas Suprarrenais/cirurgia , Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/estatística & dados numéricos , Doenças das Glândulas Suprarrenais/epidemiologia , Hiperaldosteronismo , Hiperaldosteronismo/cirurgia , Feocromocitoma , Feocromocitoma/cirurgia , Complicações Pós-Operatórias , Síndrome de Cushing/cirurgia , Síndrome de Cushing/epidemiologiaRESUMO
Se hace una revision del estado actual del sindrome de Cushing. Se pone enfasis en diferenciar las tres principales causas del sindrome. Es importante, ante la sospecha del mismo, determinar bioquimicamente su presencia. Con la introduccion de finas pruebas con inmunoensayo, al alcance de muchos laboratorios, es rápida la confirmacion del diagnostico. Conociendo los niveles plasmáticos de cortisol y de ACTH y el cortisol libre en la orina de 24 horas, se puede establecer si el sindrome es ACTH dependiente o independiente (adrenal). Gracias al perfeccionamiento de la imaginologia radiologica, la TAG o CT abdominal y la RM o MRI de la hipofisis, la localizacion de la causa se ha facilitado en el 95 por ciento de los casos. La hipofisectomia anterior trasesfenoidal y la adrenalectomia uni o bilateral, segun el cuadro clinicopatologico, permiten mejorar el pronostico de esta entidad.
Assuntos
Síndrome de Cushing/cirurgia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/terapiaRESUMO
Cushing's syndrome occurs rarely; in analyzing 50 cases studied at our institution we discuss the following aspects: syndromatic diagnosis, etiologic differentiation into the 3 categories of the syndrome, and therapeutic strategies for each variety. We postulate that non-endocrinologists should be responseible for the syndromatic diagnosis, easily done by using 2 simple tools: the measurement of basal free urinary cortisol and the performance of and overnight suppression of the adrenal axis with 1 mg of dexamethasone (Nugent's test). In contrast, the etiologic diagnosis and the therapeutic interventions should be strictly restricted to highly specialized institutions having well seasoned endocrinologists, a reliable endocrine laboratory, easy access to computed tomographies of the brain and abdomen as well as to nuclear resonance imaging of the brain. The usefulness of our in-house devised vasopressin challenge following overnight dexamethasone suppression for the etiologic diagnosis is highlighted. Neurosurgical expertise in the transphenoidal approach to the pituitary gland as well surgeons well experience in adrenal surgery sre a must to offer a reasonable chance of success to patients with the syndrome. Forty one (82 percent) of the series were female patients, 78 percent were pituitary-depent and 22 percent pituitary-independent Cushings. Six out of 8 (75 percent) of the adrenal tumors were carcinomas. Only 3 patients (6 percent) qualified as ectopic ACTH syndormes. The easiest variety to diagnose and treat was the adrenal adenoma (2 cases); adrenal carcinomas were always incurable. The ectopic ACTH syndrome was amenable to successful medical treatment with ketoconazole or surgical resolution with complete resection od the offending tumor (1 of 3 cases) or bilateral adrenalectomy (2 of 3 cases) Pituitary-dependent Cushing are quite tricky to diagnose and difficult to treat. Transphenoidal resection of the offending microadenoma was successful in only 43.5 percent (10/23) of cases and we experienced 3 recurrences of the syndrome even after 8 years of successful removal of the pituitary adenoma. The remainder had to be cured by bilateral adrenalectomy. Seven out 39 patients with Cushing's disease (18 percent) ultimately died for a variety of reasons; six out of 6 patients (100 percent) with adrenal carcinoma died of dissemination; 2 out of 2 adrenal adenomas cured and 1 out of the 3 ectopic ACTH syndromes died of dissemination of a malignant thymic carcinoma. We conclude that Cushing's syndrome is a serious, underdiagnosed disorder, which should be suspected and diagnosed by the non specialized physician and then referred to a specialized center for expert etiologic diagnosis and surgical therapy
Assuntos
Humanos , Síndrome de Cushing/diagnóstico , Dexametasona , Hidrocortisona/urina , Vasopressinas , Neoplasias do Córtex Suprarrenal/complicações , Hormônio Adrenocorticotrópico , Espectroscopia de Ressonância Magnética/métodos , Síndrome de Cushing/epidemiologia , Testes de Função do Córtex Suprarrenal/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
The clinical manifestations and the surgical treatment results of 280 patients (179 female), undergoing a total of 319 operations at the Asenjo Institute of Neurosurgery were retrospectively analyzed. The surgical approach for the first operation was transphenoidal in 89.3 per cent of patients and transcraneal in the rest. Tumors were non secretory in 169 (60.4 per cent)patients, prolactinomas in 75 (27.8 per cent) and produced acromegalia in 29 (10.4 per cent) and Cushing syndrome in 7 (2.5 per cent) patients. There was extraselar extension in 42 per cent of women and 71 per cent of men. The surgical treatment of prolactinomas corrected endocrine alterations in 25 of 29 and visual alterations in 18 of 27 patients assessed. Surgical treatment of acromegalia improved endocrine alterations in 11 of 13 and visual alterations in 4 of 10 patients assessed. Treatment of non secretory tumors corrected visual alterations in 38 of 64 patients assessed. The principal complication of transphenoidal surgery was transient diabetes insipidus in 6.8 per cent of patients. Overall mortality was 2.3 per cent for transphenoidal surgery and 5.6 per cent for transcraneal surgery. It is concluded that transphenoidal surgery is effective for the management extraselar complications of pituitary tumors and endocrine management of selected cases
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Prolactinoma/epidemiologia , Hipofisectomia , Complicações Pós-Operatórias/epidemiologia , Acromegalia/epidemiologia , Hipofisectomia/efeitos adversos , Hipofisectomia/mortalidade , Irradiação Hipofisária , Síndrome de Cushing/epidemiologiaRESUMO
Se presentan 20 pacientes adultos operados por hiperfunción corticosuprarrenalÑ 9 mostraron síndrome de Cushing (5 adenomas y 4 carcinomas), 6 hiperplasias por enfermedad de Cushing, 2 virilización, 2 hiperaldosteronismo y 1 feminización, confirmados por análisis de laboratorio. La TAC fue el método de localización preoperatorio de tumores adrenales más útil. Se encontró diferencia significativa en edad, duración de los síntomas y tamaño del tumor entre los pacientes con hipercortisolismo debido a adenoma y aquellos con carcinoma. La resección quirúrgica ofreció la curación a los pacientes con patología benigna, y un aceptable control de la enfermedad en carcinomas.