Polimiopatia hipocalêmica e hipertensão secundária a hiperaldosteronismo primário felino / Hypokalemic polymyopathy and secondary hypertension to feline primary hyperaldosteronism

O hiperaldosteronismo se define pela hipersecreção de aldosterona pelas suprarrenais, resultando em excesso de sódio e redução de potássio sanguíneo. Esta hipersecreção deve-se à síntese autônoma de aldosterona por células adrenais hiperplásicas ou neoplásicas, que agem independentemente da estimulação pelo sistema renina-angiotensina. A doença acomete felinos de adultos maduros a idosos. O excesso de aldosterona culmina em hipertensão sistêmica e/ou hipocalemia, que levam à fraqueza muscular e alterações oculares. O diagnóstico é baseado em exames laboratoriais e de imagem, e o tratamento pode ser clínico ou cirúrgico. O prognóstico é considerado favorável quando as medicações são capazes de melhorar as manifestações clínicas ou quando é possível realizar o procedimento cirúrgico. O presente trabalho visa relatar o caso de um felino macho de 13 anos, castrado, sem raça definida, com hipocalemia persistente secundária a um presuntivo tumor adrenal.

Hyperaldosteronism is defined by the hypersecretion of aldosterone by the adrenal glands resulting in excess sodium and reduced blood potassium. This hypersecretion is due to the autonomous synthesis of aldosterone by hyperplastic or neoplastic adrenal cells, which act independently of stimulation by the renin-angiotensin system. The disease affects felines in the age group from mature adults to the elderly. The excess of aldosterone culminates in systemic hypertension and/or hypokalemia, which leads to muscle weakness and ocular changes. The diagnosis is based on laboratory and imaging tests and treatment can be clinical or surgical. The prognosis is considered favorable when the medications are able to improve the clinical manifestations or when it is possible to perform the surgical procedure. The present paper aims to report the case of a 13-year-old male cat, castrated, crossbred, with persistent hypokalemia secondary to a presumptive adrenal tumor.

Conducta ante un incidentaloma suprarrenal / Behavior to be adopted to face adrenal incidentaloma

El incidentaloma suprarrenal en la actualidad es uno de los dilemas diagnóstico-terapéuticos mas frecuentes en la Endocrinología. Tiene un pico de aparición entre los 50 y los 70 años de edad, y se asocia a una mayor frecuencia de obesidad, diabetes mellitus e hipertensión arterial. La etiología es diversa, pero alrededor del 80 por ciento son adenomas benignos no funcionantes. A pesar de ello, la aparición de un carcinoma (por su agresividad) y disfunción hormonal (por la repercusión desfavorable sobre algunos factores de riesgo cardiovascular y el sistema óseo), pueden ensombrecer el pronóstico. La conducta estará basada en las definiciones mencionadas: naturaleza y función, y las 2 modalidades más empleadas son la cirugía adrenal (de preferencia laparoscópica, excepto si el tumor tiene criterios imagenológicos de malignidad); y la conservadora, que conlleva un seguimiento de, al menos, 5 años. El conocimiento de sus características, puede favorecer el mejor tratamiento a los pacientes con diagnóstico de un tumor suprarrenal incidental, y la garantía de una mejor calidad de vida(AU)

Adrenal incidentaloma is at present one of the commonest diagnostic/therapeutic dilemmas in endocrinology. It mainly occurs in the 50 to 70 years age group and is associated to higher frequency of obesity, diabetes mellitus and blood hypertension. Its etiology is varied, but around 80 percent of them are benign non-functioning adenomas. Despite the above-mentioned, the occurrence of carcinoma (based on aggressiveness) and hormonal dysfunction (negative impact on some cardiovascular risk factors and on the osseous system) can make prognosis gloomy. The behavior to be adopted will consider the stated definitions: nature and function, and the most used variants are adrenal surgery (mainly laparoscopic, except for a tumor with imaging-based malignancy criteria) and conservative surgery that implies at least five-year follow-up of the patient. Knowledge about the characteristics of adrenal incidentaloma may support a best treatment for patients suffering incidental adrenal tumor and assure them a better quality of life(AU)

Escore clínico-patológico para predizer o risco de metástases e recorrência local em pacientes com carcinoma cortical adrenal e papel do algoritmo da reticulina na distinção entre adenomas e carcinomas corticais adrenais / Clinicopathological score for predicting the risk of metastases and local recurrence in patients with adrenal cortical carcinoma and role of the reticulin algorithm in distinguishing between adrenal cortical adenomas and carcinomas

INTRODUÇÃO: o padrão-ouro para o diagnóstico histológico dos tumores corticais adrenais (TCAs) e sua diferenciação entre adenomas e carcinomas é o sistema de Weiss, cuja aplicação é limitada pela baixa reprodutibilidade de alguns dos critérios que o compõe. Recentemente foi proposto e validado um algoritmo diagnóstico para os TCAs baseado na integridade do arcabouço de reticulina e da membrana basal. Os carcinomas adrenais são tumores raros e apresentam prognóstico reservado, mesmo nos pacientes com doença aparentemente localizada. Além do estadiamento e da extensão da ressecção cirúrgica, outros dados foram reportados na literatura como tendo importância prognóstica, tais como idade ao diagnóstico, padrão funcional, tamanho tumoral, extensão local do tumor primário e alguns achados histológicos e imuno-histoquímicos, com destaque à taxa mitótica e ao índice de Ki-67. O sistema de Weiss, embora permita o diagnóstico diferencial entre adenomas e carcinomas, não foi testado completamente como uma ferramenta para distinguir os carcinomas com boa evolução clínica daqueles com desfecho desfavorável. OBJETIVOS: o presente estudo teve como objetivo primário construir um nomograma para estimar o risco de metástases e recorrência local em portadores de carcinoma adrenal, a partir de dados clínico-patológicos. O objetivo secundário foi avaliar o desempenho do algoritmo da reticulina no diagnóstico diferencial entre adenomas e carcinomas do córtex adrenal. MÉTODOS: para a construção do nomograma, foram analisados dados clínico-patológicos de 129 portadores de carcinomas adrenais atendidos no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 1976 e 2010. A avaliação do desempenho do algoritmo da reticulina para o diagnóstico histológico dos TCAs foi feita a partir do exame de 89 lâminas (45 adenomas e 44 carcinomas adrenais)...

INTRODUCTION: The gold standard for the histological diagnosis of adrenal cortical tumors (ACTs) and for the differentiation between adenomas and carcinomas is the Weiss system, whose application is limited by poor reproducibility of some of its criteria. Recently, a diagnostic algorithm for ACT diagnosis based on the integrity of the reticulin network and the basal membrane has been proposed and validated. Adrenal carcinomas are rare tumors and have a poor prognosis, even in patients with apparently localized disease. Besides tumor staging and extent of surgical resection, other data have been reported in the literature as having prognostic importance, such as age at diagnosis, the functional pattern, tumor size, local extension of the primary tumor and some histological and immunohistochemical findings, such as the mitotic rate and the Ki-67 index. The Weiss system, while allowing the differential diagnosis between adrenal cortical adenomas and carcinomas, has not been fully tested as a tool for distinguishing carcinomas with favorable clinical outcome from those with unfavorable outcome. OBJECTIVES: The primary objective of this study was to construct a nomogram for estimating the risk of metastasis and local recurrence in patients with adrenal cortical carcinoma, based on clinical and pathological data. The secondary objective was to evaluate the performance of the reticulina algorithm in the differential diagnosis between adenomas and carcinomas of the adrenal cortex. METHODS: For the construction of the nomogram, clinical and pathological data from 129 patients with adrenal cortical carcinomas treated at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo between 1976 and 2010 were analyzed. The evaluation of the performance of the reticulin algorithm for the histological diagnosis of ACTs was made from the examination of 89 slides (45 adenomas and 44 adrenal carcinomas)...

Changes in the clinical manifestations of primary aldosteronism

BACKGROUND/AIMS: Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. METHODS: In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. RESULTS: The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. CONCLUSIONS: PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.

Aldosterone- and cortisol-co-producing adrenal adenoma without clinical features of Cushing syndrome

No abstract available.

Myxoid Adrenocortical Adenoma: Magnetic Resonance Imaging and Pathology Correlation

We report a case of a 74-year-old female with myxoid adrenocortical adenoma which showed different magnetic resonance imaging findings compared to those of a typical adrenocortical adenoma. The myxoid change in the adrenocortical adenoma is a rare form of degeneration. It presents a considerable diagnostic challenge to both radiologists and clinicians because it can mimic other adrenal tumor types on imaging. The MRI findings of the presented case included a high signal intensity on T2-weighted images similar to that of fluid and delayed progressive enhancement.

Tumores adrenocorticais na criança: da abordagem clínica à avaliação molecular / Childhood adrenocortical tumors: from a clinical to a molecular approach

Tumores do córtex adrenal (TCA) são mais frequentes em crianças, mas podem ocorrer em qualquer faixa etária. São classificados como funcionantes, não funcionantes (predominam no adulto), e mistos. O diagnóstico é baseado na avaliação clínica, hormonal e exames de imagem. Em crianças, o método de escolha para diferenciar entre benigno ou maligno é a classificação baseada no estadiamento do tumor. Alguns marcadores moleculares merecem destaque: além de mutações inativadoras no gene supressor tumoral TP53, há evidências de envolvimento do IGF2 em 90 por cento de TAC malignos, e mutações no éxon 3 do gene CTNNB1 foram encontradas em 6 por cento dos TAC pediátricos. Além disso, microRNAs podem atuar como reguladores negativos da expressão gênica e participar da tumorigênese adrenocortical. Métodos para análise da expressão gênica permitem identificar TCA com prognóstico bom ou ruim, e espera-se que esses estudos possam facilitar o desenvolvimento de drogas para tratar pacientes de acordo com as vias de sinalização específicas que estiverem alteradas.

Adrenocortical tumors (ACT) are more frequent during childhood, but they can appear at any age. ACTs can be classified in functioning, nonfunctioning (mainly observed in adults) and mixed. The diagnosis is based on clinical, biochemical findings and imaging. In children, in order to classify ACT as benign or malignant, tumor staging classification is recommended. Regarding molecular markers some studies should be taken into account: besides TP53 mutations, previous studies have also provided evidences of IGF2 involvement in 90 percent of the malignant ACT. Mutations altering exon 3 of CTNNB1 gene have been found in 6 percent of childhood ACTs. In addition, microRNAs can act as negative regulators of gene expression by targeting mRNA controlling cell growth, differentiation and apoptosis and have been implicated in adrenal tumorigenesis. High-throughput methods to analyze genome-wide expression have been developed over the last decade and identified a subset of tumors with good or poor prognosis. In the future, these studies can provide the basis of specific drug development, which can treat patients according to specific altered signaling pathway.

Síndrome de Conn: descripción de dos casos clínicos / Conn`s syndrome: two case reports

El hiperaldosteronismo primario es una de las formaspotencialmente curables de hipertensión arterial. Solía ser considerado un trastorno poco común, pero algunos expertos creen que puede ser la causa de hipertensión en un 5% a un14% de los pacientes. En la mayoría de los casos resulta de un tumor benigno de la glándula suprarrenal y se presenta en personas entre los 30 y 50 años de edad. En estos casos, la HTA es secundaria a la acción de aldosterona a nivel renal, la cual determina un aumento en la reabsorción de sal y agua, lo que se traduce en un aumento del volumen intravascular y secundariamente en elevación de la presión arterial.

Primary hyperaldosteronism is one of the potentially curable forms of arterial hypertension. It used to be considered an uncommon problem, but some experts believe it can be the cause of hypertension in 5 to 14% of patients. In most cases it is a benign tumor of the adrenal glands, appearing between ages 30 and 50 years. In these cases, hypertension is secondary to the action of aldosterone at the renal level, resulting in an increase in the reabsorption of salt and water, which is translated secondarily to an increase in the intravascular volume and an elevation of arterial pressure.

MDCT and Gd-EOB-DTPA Enhanced MRI Findings of Adrenal Adenoma Arising from an Ectopic Adrenal Gland within the Liver: Radiologic-Pathologic Correlation

We report a case of an adenoma arising from an ectopic adrenal gland mimicking a hepatocellular carcinoma in a heavy alcohol abuser. A MDCT showed a 2.7 low-attenuating nodule in segment VII of the liver through all CT phases. Compared to a precontrast image, however, a subtle enhancement was noted on the arterial phase CT image. On T1 weighted in- and opposed-phase MR images, an abundant fat component within the lesion was seen. Dynamic contrast-enhanced MR images after administration of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) more clearly depicted hypervascularity and wash-out of the lesion on arterial and portal phases, respectively. On delayed hepatobiliary phase MR images, obtained 20 minutes after Gd-EOB-DTPA administration, subtle uptake or retention of the contrast agent by the lesion was suspected. A tumorectomy was performed and adrenal adenoma from an ectopic adrenal gland within the liver was confirmed.

Síndrome de Cushing subclínica em populações de risco: [revisão] / Subclinical Cushing's syndrome in populations at risk: [review]

Os incidentalomas de adrenais (IA) são tumores freqüentes em humanos. A síndrome de Cushing (SC) endógena é rara e os adenomas de adrenais são responsáveis por 10 por cento dos casos de SC. A SC subclínica ocorre em IA com dinâmica do cortisol anormal e ausência de fenótipo característico de hipercortisolismo. A prevalência média de SC subclínica em IA é de 9 por cento. Dados de pequenas séries indicam que 20 por cento dos IA desenvolvem alterações bioquímicas quando acompanhados por 10 anos. A evolução da SC subclínica parece ser benigna, raramente ocorrendo aumento da massa e evolução para a SC clinicamente manifesta. Os incidentalomas e a SC subclínica têm sido correlacionados aos componentes da síndrome metabólica, especialmente ao diabetes mellitus do tipo 2. Embora o número de pacientes avaliados ainda seja pequeno, os estudos disponíveis demonstram que o tratamento do hipercortisolismo resulta em melhor controle metabólico e da pressão arterial. Esses achados levaram alguns autores a pesquisar a presença de SC subclínica em pacientes com diagnóstico prévio de diabetes mellitus. Os estudos realizados utilizando diferentes abordagens diagnósticas mostraram que nesse grupo de pacientes a incidência de SC subclínica é maior do que na população geral.

Based on autopsy studies, adrenal masses are among the most common tumors in humans. Endogenous Cushing's syndrome (CS) is unusual and adrenal adenomas account for 10 percent of all cases of CS. Patients with subclinical CS (SCS) present abnormal cortisol dynamics without obvious manifestations. The prevalence of hypercortisolism in clinically inapparent adrenal masses has been reported as 9 percent. Data from several small series of patients indicate that fewer than 20 percent develop hormone overproduction when followed for up to 10 years. Follow-up of patients with subclinical CS suggests that rarely masses increase in size or progress to overt CS. Adrenal incidentalomas and subclinical CS are related to metabolic disorders, in special to type-2 diabetes. The scarce available data suggest that treatment of hypercortisolism correct the metabolic abnormalities and blood pressure. Some studies evaluating the prevalence of subclinical CS in overweight type-2 diabetes patients suggest that it is considerably higher in populations at risk than in the general population.

Hiperaldosteronismo primário causado por aldosteronoma: problemas no diagnóstico etiológico / Primary aldosteronism caused by aldosteronoma: problems in the etiologic diagnosis

O hiperaldosteronismo primário (HAP) representa importante causa de hipertensão arterial secundária, potencialmente curável, que tem recebido atenção recente em função do aumento de sua prevalência desde a introdução do rastreamento pelo uso da relação aldosterona/atividade plasmática de renina. Apresentamos caso de HAP causado por provável aldosteronoma, coexistente com adenoma adrenal não-funcionante contra-lateral, o que dificultou o diagnóstico etiológico. Discutimos as formas mais apropriadas de rastrear, confirmar o diagnóstico de HAP e diferenciar as suas diversas etiologias, com destaque para o papel do cateterismo de adrenais no diagnóstico diferencial definitivo entre aldosteronoma e hiperaldosteronismo idiopático, com implicações no sucesso terapêutico.

Primary aldosteronism (PA) represents an important cause of secondary hypertension, potentially curable, and it has been receiving particular attention due to its increasing prevalence, after the beginning of the use of plasma aldosterone concentration to plasma renin activity ratio as a screening method. We present a case of PA caused by an aldosteronoma associated with a contralateral nonfunctioning adrenal adenoma, which resulted in difficulties in the final diagnosis. We discuss the most appropriated tests to screen, confirm the diagnosis of PA and define the etiology of the disorder, especially the adrenal veins sampling to distinguish the aldosteronoma and idiopathic hyperaldosteronism and to guide successful treatment.

[Carney complex: a case report from Iran]

Carney Complex is an autosomal dominant syndrome that is defined with different tumors including myxoma in different organs, endocrine tumors and lentiginosis lesions. This is the first case report of this syndrome from Iran. Case: The patient is a 27 year old girl, referred with flank pain. Physical examination revealed hirsutism, truncal obesity, hyperpigmantasion and hypertension; Cushing's syndrome was suggested and confirmed with related classic biochemical tests. She had history of cardiac myxoma during her childhood and had been operated twice. Pituitary microadenoma and right adrenal adenoma were reported on MRI and CT-scan, respectively. Initially laparascopic right adrenalectomy was done; as expected, no remission in signs of Cushing's syndrome was observed after surgery. By laparoscopic adrenalectomy of the other site, Cushing's syndrome resolved. Pathologic report of 1st operation was adrenal adenoma with surrounding pigmented micronodular hyperplasia and of the 2nd one was just pigmented micronodular hyperplasia. Conclusion: We have reported a patient with Carney syndrome along with Cushing's syndrome due to bilateral adrenal hyperplasia and an adenoma in contralateral adrenal and microadenoma of the pituitary as an incidentaloma. This is a new presentation of Carney syndrome

Adrenalectomía laparoscópica / Laparoscopic adrenalectomy

Se presenta un caso clínico de una paciente portadora de un tumor funcionante de la corteza suprarrenal secretor de aldosterona. Se analiza el diagnóstico, los exámenes paraclínicos y en particular la modalidad de tratamiento por cirugía laparoscópica. El diagnóstico se planteó por la clínica y los exámenes de laboratorio (hipopotasemia e hiperaldosteronismo). Se confirmó la topografía del tumor con los exámenes imagenológicos (TAC, RMN y Centellograma), localizándose a nivel de la glándula suprarrenal izquierda. Se realizó el abordaje por cirugía laparoscópica, procediéndose a su resección. La evolución de la paciente del punto de vista quirúrgico fue excelente, normalizándose las cifras de hipertensión arterial, potasemia y aldosterona.

Clinical Study of Adrenal Incidentaloma in Korea

BACKGROUND: This study was designed to evaluate the clinical, endocrinological and histological characteristics of adrenal incidentalomas. METHODS: Eighty patients (41, males; 38, females; age range 17-80 years) who were diagnosed with adrenal incidentaloma at Korea University Hospital from 1992 to 2003 were studied retrospectively. RESULTS: Endocrinological investigation revealed 16 pheochromocytomas (20%), nine Cushing's syndromes (11%), eight primary aldosteronism (10%) and 46 non-functioning tumors (58%). Forty-four patients received operations, and biopsies were performed on two patients. Pathologic examination revealed 16 adrenocortical adenomas (20%), five carcinomas (6%), 13 pheochromocytomas (16%), three metastatic cancers (4%), and other tumors (10%). The diameter of the carcinomas (mean: 10.8 cm, range: 5-19 cm) were significantly larger than the diameter of benign adenomas (mean: 2.84 cm, range: 1-6 cm) (p=0.002). According to the receiver operating charactenstic (ROC) curve analysis, the cut-off value of tumor size for discriminate malignant tumor was 4.75 cm (sensitivity 90%, specificity 58%). Twenty-four patients with non-functioning tumors were followed up for a period of 3 to 72 months. During the follow up period, two patients showed an increase in tumor size of more than 1 cm, and one patient developed Cushing's syndrome. Changes in mass size and function were observed only between 10 and 26 months after the initial diagnosis. CONCLUSIONS: These data show that an endocrine evaluation should be performed in all adrenal incidentalomas, and an adrenalectomy is recommended for tumors 5 cm or greater or tumors with adrenocortical hyperfunction. In addition, these tumors should be monitored for changes in mass size and function for a follow up period of approximately 26 months.

Tumores da córtex da supra-renal: o uso do p53 na diferenciaçäo entre carcinomas e adenomas / Adrenocortical tumors: use of p53 in differentiation between carcinomas and adenomas

A marcação imunohistoquímica da proteina p53 foi estudada em tumores da adrenal conservados em formol ou em blocos de parafina, pelo método da avidina-biotina-peroxidase com recuperação antigênica. Foram estudados 24 carcinomas e 26 adenomas com o objetivo de verificar se o marcador mostrava capacidade de distinção entre eles. Em 62,5 por cento dos carcinomas a marcação foi positiva enquanto que nos adenomas foi de 15,4 por cento, diferença essa estatisticamente significante (p=0,0003). A sensibilidade, especificidade e valor preditivo positivo desse marcador para o diagnóstico do câncer foram, respectivamente: 83,3 por cento, 71,8 por cento e 62,5 por cento. Não houve relação entre o índice de marcação e outros parâmetros clínicos, como peso do tumor, estádio local, recidiva e metástases. Os autores concluem que o marcador é útil no diagnóstico diferencial de massas da adrenal, mas não tem relação com a agressividade biológica da neoplasia maligna.

A clinicopathologic profile of adrenocortical tumors.

OBJECTIVE: To study the clinical, biochemical, hormonal, radiological and histopathological profile of adrenocortical tumors in children; to assess the clinicopathological correlations and note the future outcome. DESIGN: Retrospective and prospective study. SETTING: Hospital based; Endocrine Service of our institution and other institution based services. SUBJECTS: 14 children (Females = 11, Males = 3) with adrenocortical tumor, aged 8 months to 13 years (mean age 5.1 +/- 3.42 years), seen over a period of 9 years. RESULTS: Females predominated (F:M = 3.7:1). Majority (64%) had a mixed picture with cushingoid features and virilization, whereas 36% presented only for virilization. Elevated serum cortisol levels with loss of diurnal variation was noted only in those with mixed clinical presentation. Adrenal androgen elevation was noted in majority of cases as virilization was common to all. CT confirmed the diagnosis of tumor, 7 on either side. Thirteen cases were operated. Histopathologic diagnosis was carcinoma in 7 and adenoma in 6 cases. Three of the seven with carcinoma died within 3 months to 2 years but two of these with small tumours (weight 60-65 g and diameter < 6 cm) were well at 2 and 5 years, while as one of the six with a large adenoma had recurrence and metastasis after three years. CONCLUSION: Female preponderance was marked (4 times), 43% of tumors had occurred by 3 years of age and 64% by 6 years. Neither the hormonal parameters nor the histopathology correlated well with the biological behavior and outcome. Prolonged and vigilant follow up is essential.