Malignancy must be considered in the management of adrenal lesions, including those incidentally identified on imaging studies. Adrenocortical carcinomas (ACCs) are rare tumors with an estimated annual incidence of 0.7-2 cases per year and a worldwide prevalence of 4-12 cases per million/year. However, a much higher incidence of these tumors (>15 times) has been demonstrated in south and southeastern Brazil. Most ACCs cause hypersecretion of steroids including glucocorticoids and androgens. ACC patients have a very poor prognosis with a 5-year overall survival (OS) below 30% in most series. Pheochromocytoma or paraganglioma (PPGL) is a metabolically active tumor originating from the chromaffin cells of the adrenal medulla. The incidence of PPGL is 0.2 to 0.9 cases per 100,000 individuals per year. Pheochromocytomas are present in approximately 4-7% of patients with adrenal incidentalomas. Classically, PPGL manifests as paroxysmal attacks of the following 4 symptoms: headaches, diaphoresis, palpitations, and severe hypertensive episodes. The diagnosis of malignant PPGL relies on the presence of local invasion or metastasis. In this review, we present the clinical and biochemical characteristics and pathogenesis of malignant primary lesions that affect the cortex and medulla of human adrenal glands.

OBJECTIVES: Transcription Factor 21 represses steroidogenic factor 1, a nuclear receptor required for gonadal development, sex determination and the regulation of adrenogonadal steroidogenesis. The aim of this study was to investigate whether silencing or overexpression of the gene Transcription Factor 21 could modulate the gene and protein expression of steroidogenic factor 1 in adrenocortical tumors. METHODS: We analyzed the gene expression of steroidogenic factor 1 using qPCR after silencing endogenous Transcription Factor 21 in pediatric adrenal adenoma-T7 cells through small interfering RNA. In addition, using overexpression of Transcription Factor 21 in human adrenocortical carcinoma cells, we analyzed the protein expression of steroidogenic factor 1 using Western blotting. RESULTS: Transcription Factor 21 knockdown increased the mRNA expression of steroidogenic factor 1 by 5.97-fold in pediatric adrenal adenoma-T7 cells. Additionally, Transcription Factor 21 overexpression inhibited the protein expression of steroidogenic factor 1 by 0.41-fold and 0.64-fold in two different adult adrenocortical carcinoma cell cultures, H295R and T36, respectively. CONCLUSIONS: Transcription Factor 21 is downregulated in adrenocortical carcinoma cells. Taken together, these findings support the hypothesis that Transcription Factor 21 is a regulator of steroidogenic factor 1 and is a tumor suppressor gene in pediatric and adult adrenocortical tumors.

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.

Diversas mutações em oncogenes promovem o crescimento tumoral através da indução de atividade de proteínas que normalmente transmitem sinais proliferativos a partir de fatores extracelulares. As proteínas G são uma família de proteínas ligadas ao nucleotídeo guanina que apresentam homologia estrutural e estão amplamente distribuídas em células eucariotas. Elas são constituídas por três sub-unidades (alfa, beta e gama). A sub-unidade alfa apresenta o sítio de ligação ao nucleotídeo guanina e é única para cada proteína G. A proteínas G estão acopladas aos receptores de superfície celular com sete hélices transmembrana com uma grande variedade de efetores intracelulares e segundos mensageiros. Um subgrupo de tumores endócrinos, incluindo os tumores hipofisários secretores de GH e ACTH, nódulos tireoideanos autônomos, tumores adrenocorticais e gonadais, foram associados a mutações somáticas ativadoras em códons altamente conservados das proteínas Gs (Arg201 e Gln227) e Gi (Arg179, Gln205). Estes achados moleculares indicaram que as proteínas G atuam como oncogenes, contribuindo no processo da tumorigênese endócrina em humanos.

Many oncogenic mutations promote tumor growth by inducing autonomous activity of proteins that normally transmit proliferative signal initiated by extracelular factors. G proteins are a family of guanine nucleotide binding proteins, which are structurally homologous and widely distributed in eukaryotic cells. They are composed of three different subunits (alpha, beta e gamma). The alpha subunit, which contains the guanine nucleotide-binding site, is unique to each G protein. The G proteins couple an array of seven transmembrane receptors at the cell surface with a variety of intracellular effectors, which produce second messenger molecules. A subset of endocrine tumors, such as GH- or ACTH-secreting pituitary adenomas, functioning thyroid adenomas, adrenocortical and gonadal tumors were associated with somatic activating mutations in the highly conserved codons of the Gs (Arg201 and Gln227) and Gi (Arg179 and Gln205) proteins. These findings indicated that the G proteins play a role as oncogenes, contributing with the human endocrine tumorigenesis.