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)...

Development and internal validation of an adrenal cortical carcinoma prognostic score for predicting the risk of metastasis and local recurrence.

OBJECTIVE: To develop and internally validate a prognostic score to predict the risk of metastases or recurrence in patients with adrenal cortical carcinomas (ACC). DESIGN: Clinical, laboratory and pathological data from 129 ACC patients, treated in a tertiary centre, were retrospectively reviewed. RESULTS: Using a multivariate binary logistic regression analysis, we developed a prognostic score with five covariates: a functional pattern other than isolated hyperandrogenism, a tumour size >7·5 cm, a primary tumour classified as T3/T4, the presence of microscopic venous invasion and a mitotic index >5/50 high-power fields. The prognostic score was calibrated according to the Hosmer-Lemeshow goodness-of-fit test (P = 0·9329) and exhibited excellent overall performance (Brier score = 0·0738). Finally, the discriminatory ability of the model, determined by the area under the ROC curve (AROC ), was near perfect (AROC , 0·9611; 95% CI, 0·92676-0·99552). The prediction model was internally validated with 200 bootstrap resamples and achieved excellent performance for estimating the risk of metastasis and recurrence in eight additional patients with apparently localized disease at diagnosis. CONCLUSION: We developed and internally validated a prognostic score based on the clinicopathological data that are readily available to any attending physician. Our model can be used to accurately estimate the risk of unfavourable outcomes in ACC patients. This score could be beneficial for both patient counselling and the identification of patients in whom adjuvant mitotane is justified.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene / Síndrome de hiperinsulinemia/hiperamonemia devido a uma mutação no gene da glutamato desidrogenase

The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease manifested by hypoglycemic symptoms triggered by fasting or high-protein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypoglycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exon-intron boundary regions of the GLUD1 gene, were performed in a 6-year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

A síndrome de hiperinsulinemia/hiperamonemia (HI/HA) é uma condição rara, de herança autossômica dominante, que se manifesta por sintomas de hipoglicemia desencadeada por jejum ou refeições de alto conteúdo proteico, juntamente com elevação da concentração de amônia sérica. HI/HA é a segunda causa de hipoglicemia hiperinsulinêmica da infância e é causada por mutações ativadoras no GLUD1, o gene que codifica a enzima mitocondrial glutamato desidrogenase (GDH). A avaliação bioquímica, bem como o sequenciamento direto dos éxons e junções éxon-íntron do gene GLUD1, foi realizada em uma paciente de 6 anos de idade com hipoglicemia de jejum e hiperamonemia. A paciente apresentava uma mutação de novo missense (c.1491A>G; p.Il497Met) em heterozigose, que havia sido previamente relatada em um paciente japonês. O tratamento com diazóxido 100 mg/dia promoveu resolução completa dos episódios hipoglicêmicos. Arq Bras Endocrinol Metab. 2012;56(8):485-9.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene.

The hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disease manifested by hypoglycemic symptoms triggered by fasting or high-protein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypoglycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exon-intron boundary regions of the GLUD1 gene, were performed in a 6-year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes.

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

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.

[Nelson's Syndrome: a case report]. / Síndrome de Nelson: relato de caso.

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.

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.

Síndrome de Nelson: relato de caso / Nelson's Syndrome: a case report

O objetivo deste artigo é apresentar e discutir alguns aspectos da patogênese, do diagnóstico clínico, hormonal e radiológico e do tratamento da síndrome de Nelson, com base no relato de um paciente típico portador da doença, no qual várias abordagens terapêuticas mostraram-se ineficazes.

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.

Feocromocitoma / Pheochromocytoma

Apresentamos a experiência do Hospital das Clínicas da FMUSP, com o diagnóstico clínico, laboratorial e topográfico e com o tratamento do feocromocitoma. Embora novos testes bioquímicos, como as determinações de metanefrinas plasmáticas, tenham maior sensibilidade no diagnóstico desse tumor, testes mais disponíveis, como as determinações de metanefrinas urinárias e catecolaminas plasmáticas e urinárias ainda demonstram grande valor no diagnóstico. Eventuais falso-negativos e falso-positivos podem ser identificados com os testes de estímulo e depressão e com a exclusão do uso de droga. A ressonância magnética é o método mais sensível na identificação topográfica do tumor. O tratamento do tumor, exceto quando houver contraindicações, é sempre cirúgico e deve ser precedido pelo tratamento clínico. A identificação desse tumor é de fundamental importância no sentido de se prevenir a ocorrência de eventos com alta morbidade e mortalidade, bem como na identificação de outras síndromes neoplásicas que podem estar associadas a ele.

[Pheochromocytoma]. / Feocromocitoma.

We present the experience of Hospital das Clínicas, FMUSP, with the clinical, biochemical and topographic diagnosis of pheochromocytoma, as well as the therapeutic approaches. Although new biochemical tests, as plasma metanephrines determination, have greater sensibility in the diagnosis of this tumor, more feasible tests, such as urinary metanephrines and urinary and plasma catecholamines, still have important diagnostic value. Eventual false-negative and false-positive results can be identified with stimulation and suppression tests and drug withdrawal. Magnetic resonance imaging has the greatest sensibility for the topographic diagnosis. In the absence of absolute contraindications, treatment is always surgical, and should be preceded by clinical therapy. Precise diagnosis of this tumor is important to prevent cardiovascular events that imply high morbidity and mortality, as well as to identify other neoplastic syndromes that may be associated.