RESUMO
Adrenocortical carcinoma (ACC) is an orphan cancer with 35% five-year survival that has been unchanged for last five decades. Patients often present with severe hypercortisolism or with mass effects. The only Food and Drug Administration (FDA)-approved drug for ACC is mitotane, an insecticide derivative, which provides only limited additional months of survival, but with toxicities. Little progress in the field has occurred due to a lack of preclinical models. We recently developed new human ACC in vitro and in vivo research models. We produced the first two new ACC cell lines for the field, CU-ACC1 and CU-ACC2, which we have distributed for global collaborations. In addition, we developed 10 ACC patient-derived xenograft (PDX) and two humanized ACC-PDX models to test new therapeutics and examine the mechanism of mitotane action in combination with immunotherapy. These new preclinical models allow us to identify novel targets and test new therapeutics for our patients with adrenal cancer.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Mitotano , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/terapia , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Animais , Mitotano/uso terapêutico , Doenças Raras/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos , Antineoplásicos Hormonais/uso terapêuticoRESUMO
INTRODUCTION: Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy. MATERIAL AND METHODS: This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results. RESULTS: The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children. CONCLUSIONS: The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Antineoplásicos Hormonais , Mitotano , Puberdade Precoce , Humanos , Puberdade Precoce/tratamento farmacológico , Puberdade Precoce/induzido quimicamente , Mitotano/uso terapêutico , Mitotano/efeitos adversos , Feminino , Carcinoma Adrenocortical/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Estudos Retrospectivos , Masculino , Pré-Escolar , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Lactente , Criança , Doenças do Sistema Endócrino/induzido quimicamenteAssuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Antineoplásicos Hormonais , Mitotano , Humanos , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Feminino , Criança , Masculino , Adolescente , Terapia de Reposição HormonalRESUMO
Background: Adrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies. Objective: We aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC. Methods: In vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing. Results: PDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P<0.0001; AUC: 158.0 vs 213.5, P<0.0001). Genomic analysis revealed CTNNB1 somatic alterations were only found in responders (3/5) while ZNRF3 alterations only in non-responders (3/4). Transcriptomic profiling found pathways associated with lipid metabolism were upregulated in responder tumors whilst CYP27A1 and ABCA1 expression were positively correlated to in vitro mitotane sensitivity. Furthermore, pharmacologic analysis identified that compounds including disulfiram, niclosamide and bortezomib exhibited efficacy against PDCs. Conclusion: ACC PDCs could be useful for testing drug response, drug repurposing and guiding personalized therapies. Our results suggested response to mitotane might be associated with the dependency on lipid metabolism. CYP27A1 and ABCA1 expression could be predictive markers for mitotane response, and disulfiram, niclosamide and bortezomib could be potential therapeutics, both warranting further investigation.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Antineoplásicos Hormonais , Mitotano , Testes Farmacogenômicos , Humanos , Mitotano/uso terapêutico , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/metabolismo , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/metabolismo , Feminino , Masculino , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Pessoa de Meia-Idade , Adulto , Idoso , FarmacogenéticaAssuntos
Neoplasias do Córtex Suprarrenal , Anilidas , Mitotano , Piridinas , Humanos , Piridinas/uso terapêutico , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Anilidas/uso terapêutico , Carcinoma Adrenocortical/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Resultado do TratamentoRESUMO
While suggested, surgery is not always possible as a first-line treatment of Cushing's Disease (CD). In such cases, patients require medical therapy in order to prevent complications resulting from hypercortisolism. Although there has been a wide expansion in pharmacological options in recent years, mitotane was the agent of choice for treating hypercortisolism decades ago. Due to the introduction of other therapies, long-term experience with mitotane remains limited. Here, we report the case of a woman with CD who was treated with mitotane for 37 years. During the treatment period, biochemical and clinical disease control was achieved and the patient had two uncomplicated pregnancies. Drug-related side effects remained moderate and could be controlled by several dose adjustments. Our case highlights the ability of mitotane to allow an effective control of hypercortisolism and to represent a safe treatment option in special situations where CD requires an alternative therapeutic approach. Furthermore, we provide a literature review of the long-term use of mitotane and reported cases of pregnancy in the context of mitotane therapy.
Assuntos
Síndrome de Cushing , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersecreção Hipofisária de ACTH , Feminino , Gravidez , Humanos , Síndrome de Cushing/tratamento farmacológico , Mitotano/uso terapêuticoRESUMO
Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition caused by pancreatic neuroendocrine tumors (p-NETs). The severe hypercortisolemia that characterizes EAS is associated with a poor prognosis and survival. Mitotane is the only adrenolytic drug approved by the Food and Drug Administration and is often used to treat adrenocortical carcinoma. Combination therapy with mitotane and other adrenal steroidogenesis inhibitors is common for patients with Cushing's syndrome (CS). Here, we describe three patients who developed EAS secondary to the liver metastasis of p-NETs. All three rapidly developed hypercortisolemia but no typical features of CS. They underwent anti-tumor and mitotane therapy, which rapidly reduced their blood cortisol concentrations and ameliorated their symptoms. Their hypercortisolemia was controlled long term using a low dose of mitotane. The principal adverse effects were a slight loss of appetite and occasional dizziness, and there were no severe adverse effects. Importantly, even when the tumor progressed, the patients' circulating cortisol concentrations remained within the normal range. In summary, the present case series suggests that mitotane could be used to treat hypercortisolemia in patients with EAS caused by advanced p-NETs, in the absence of significant adverse effects.
Assuntos
Síndrome de Cushing , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Estados Unidos , Humanos , Mitotano/uso terapêutico , Hidrocortisona , Síndrome de Cushing/tratamento farmacológico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Hormônio AdrenocorticotrópicoRESUMO
OBJECTIVE: Mitotane is the standard therapy of adrenocortical carcinoma (ACC) due to its relative selectivity of its cytotoxic effects toward adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. Frequency and characteristics of hypothalamic-pituitary-adrenal axis recovery after discontinuation are ill-defined. METHODS: This was a retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Primary endpoint was adrenal recovery. Cox regression analyses were used to identify predictive factors. Moreover, mitotane plasma elimination rate and hormonal changes after mitotane stop were investigated. RESULTS: Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8â g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2â mg/L, and the detection limit was 152 days (interquartile range: 114-202), 280 days (192-370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95% confidence interval [CI] = 19.6-32.4). In 4 patients (7.1%), adrenal insufficiency persisted >5 years after discontinuation. Mitotane peak ≥ 27â mg/L significantly correlated with longer time to adrenal recovery (hazard ratio [HR] = 0.2, 95% CI = 0.1-0.8, P = .03). Twenty-seven of 38 patients (71%) followed in reference centers achieved adrenal recovery compared with only 5/18 (28%) followed up in non-reference centers (HR = 4.51, 95% CI = 1.71-11.89, P = .002). Other investigated factors were not associated with adrenal function after discontinuation. CONCLUSIONS: Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long but individually quite variable.
Assuntos
Neoplasias do Córtex Suprarrenal , Insuficiência Adrenal , Carcinoma Adrenocortical , Humanos , Feminino , Carcinoma Adrenocortical/tratamento farmacológico , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/patologia , Estudos Retrospectivos , Sistema Hipotálamo-Hipofisário , Antineoplásicos Hormonais/uso terapêutico , Sistema Hipófise-Suprarrenal , Insuficiência Adrenal/tratamento farmacológicoRESUMO
Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive tumor. ACC male patients under adjuvant mitotane therapy (AMT) frequently develop hypogonadism, however sexual function has never been assessed in this setting. The aim of this retrospective study was to evaluate in AMT treated ACC patients the changes in Luteinizing hormone (LH), Sex Hormone Binding Globulin (SHBG), total testosterone (TT) and calculated free testosterone (cFT), the prevalence and type of hypogonadism and sexual function, the latter before and after androgen replacement therapy (ART). Methods: LH, SHBG, TT and cFT were assessed in ten ACC patients at baseline (T0) and six (T1), twelve (T2), and eighteen (T3) months after AMT. At T3, ART was initiated in eight hypogonadal patients, and LH, SHBG, TT and cFT levels were evaluated after six months (T4). In six patients, sexual function was evaluated before (T3) and after (T4) ART using the International Index of Erectile Function-15 (IIEF-15) questionnaire. Results: Under AMT we observed higher SHBG and LH and lower cFT levels at T1-T3 compared to T0 (all p<0.05). At T3, hypergonadotropic hypogonadism and erectile dysfunction (ED) were detected in 80% and 83.3% of cases. At T4, we observed a significant cFT increase in men treated with T gel, and a significant improvement in IIEF-15 total and subdomains scores and ED prevalence (16.7%) in men under ART. Conclusion: AMT was associated with hypergonatropic hypogonadism and ED, while ART led to a significant improvement of cFT levels and sexual function in the hypogonadal ACC patients. Therefore, we suggest to evaluate LH, SHBG, TT and cFT and sexual function during AMT, and start ART in the hypogonadal ACC patients with sexual dysfunction.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Disfunção Erétil , Hipogonadismo , Humanos , Masculino , Mitotano/uso terapêutico , Estudos Retrospectivos , Testosterona , Hormônio Luteinizante , Hipogonadismo/tratamento farmacológicoRESUMO
Adrenocortical carcinoma (ACC) is a rare and in most cases steroid hormone-producing tumor with variable prognosis. The purpose of these guidelines is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with ACC based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions, which we judged as particularly important for the management of ACC patients and performed systematic literature searches: (A) What is needed to diagnose an ACC by histopathology? (B) Which are the best prognostic markers in ACC? (C) Is adjuvant therapy able to prevent recurrent disease or reduce mortality after radical resection? (D) What is the best treatment option for macroscopically incompletely resected, recurrent or metastatic disease? Other relevant questions were discussed within the group. Selected Recommendations: (i) We recommend that all patients with suspected and proven ACC are discussed in a multidisciplinary expert team meeting. (ii) We recommend that every patient with (suspected) ACC should undergo careful clinical assessment, detailed endocrine work-up to identify autonomous hormone excess and adrenal-focused imaging. (iii) We recommend that adrenal surgery for (suspected) ACC should be performed only by surgeons experienced in adrenal and oncological surgery aiming at a complete en bloc resection (including resection of oligo-metastatic disease). (iv) We suggest that all suspected ACC should be reviewed by an expert adrenal pathologist using the Weiss score and providing Ki67 index. (v) We suggest adjuvant mitotane treatment in patients after radical surgery that have a perceived high risk of recurrence (ENSAT stage III, or R1 resection, or Ki67 >10%). (vi) For advanced ACC not amenable to complete surgical resection, local therapeutic measures (e.g. radiation therapy, radiofrequency ablation, chemoembolization) are of particular value. However, we suggest against the routine use of adrenal surgery in case of widespread metastatic disease. In these patients, we recommend either mitotane monotherapy or mitotane, etoposide, doxorubicin and cisplatin depending on prognostic parameters. In selected patients with a good response, surgery may be subsequently considered. (vii) In patients with recurrent disease and a disease-free interval of at least 12 months, in whom a complete resection/ablation seems feasible, we recommend surgery or alternatively other local therapies. Furthermore, we offer detailed recommendations about the management of mitotane treatment and other supportive therapies. Finally, we suggest directions for future research.
Assuntos
Humanos , Radioterapia , Quimioembolização Terapêutica , Ablação por Cateter , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical , Carcinoma Adrenocortical/terapia , Adrenalectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Etoposídeo/administração & dosagem , Mitotano/uso terapêutico , Metástase NeoplásicaRESUMO
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.
Assuntos
Humanos , Paraganglioma/terapia , Feocromocitoma/terapia , Neoplasias do Córtex Suprarrenal/terapia , Neoplasias das Glândulas Suprarrenais/terapia , Carcinoma Adrenocortical/terapia , Paraganglioma/diagnóstico , Paraganglioma/patologia , Feocromocitoma/diagnóstico , Feocromocitoma/patologia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/patologia , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêuticoRESUMO
The treatment of choice for Cushing's syndrome remains surgical. The role for medical therapy is twofold. Firstly it is used to control hypercortisolaemia prior to surgery to optimize patient's preoperative state and secondly, it is used where surgery has failed and radiotherapy has not taken effect. The main drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and mitotane. Drugs targeting the hypothalamic-pituitary axis have been investigated but their roles in clinical practice remain limited although PPAR-gamma agonist and somatostatin analogue som-230 (pasireotide) need further investigation. The only drug acting at the periphery targeting the glucocorticoid receptor remains Mifepristone (RU486). The management of Cushing syndrome may well involve combination therapy acting at different pathways of hypercortisolaemia but monitoring of therapy will remain a challenge.
O tratamento de escolha para a síndrome de Cushing ainda é a cirurgia. O papel da terapia medicamentosa é duplo: ele é usado para controlar o hipercortisolismo antes da cirurgia e otimizar o estado pré-operatório do paciente e, adicionalmente, quando ocorre falha cirúrgica e a radioterapia ainda não se mostrou efetiva. Os principais medicamentos são empregados para inibir a esteroidogênese e incluem: metirapona, cetoconazol e mitotano. Medicamentos visando o eixo hipotálamo-hipofisário têm sido investigados, mas seu papel na prática clínica permanece limitado, embora o agonista PPAR-gama e análogo de somatostatina, som-230 (pasireotídeo), requeira estudos adicionais. A única droga que age perifericamente no receptor glicocorticóide é a mifepristona (RU486). O manejo da síndrome de Cushing deve envolver uma combinação terapêutica atuando em diferentes vias da hipercortisolemia, mas o monitoramento dessa terapia ainda permanece um desafio.
Assuntos
Humanos , Síndrome de Cushing/tratamento farmacológico , Antagonistas de Dopamina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Cetoconazol/uso terapêutico , Metirapona/uso terapêutico , Mifepristona/uso terapêutico , Mitotano/uso terapêutico , PPAR gama/agonistas , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Somatostatina/análogos & derivados , Esteroides/antagonistas & inibidores , Esteroides/biossínteseRESUMO
Se analiza el estado actual del tratamiento médico de los tumores hipofisiarios productores de corticotrofina (ACTH) y tirotrofina (TSH). Se presentan las investigaciones comunicadas por diversos autores en el tratamiento de la enfermedad de Cushing y el síndrome de Nelson con moduladores de la secreción de ACTH, la bromocriptina, la ciproheptadina, la ritanserina, el ácido valproico y la somatostatina. Los resultados positivos cubren un pequeño número de casos. La primera opción de tratamiento de estos tumores es la cirugía seguida de la radioterapia. Cuando no se logra extirpar completamente los tumores, el uso de drogas que actúan inhibiendo la esteroidogénesis suprarrenal constituye una terapia paliativa. Entre estas drogas se cuentan el ketoconazol, la aminoglutetimida, la metopirona, el mitotano y el trilostan, con diversos grados de efectividad y tolerancia. Los pacientes que presentan tumores hipofisiarios productores de TSH han sido tratados con éxito con análogos de la somatostatina de acción prolongada, octreotide y lanreotide SR. Se ha logrado dramática supresión de la TSH y de la subunidad alfa, así como control del hipertiroidismo y disminución del tamaño de los tumores. Estas drogas ofrecen posibilidades de tratamiento médico para los pacientes que no logran control de su enfermedad con la cirugía
Assuntos
Neoplasias Hipofisárias , Síndrome de Cushing/tratamento farmacológico , Síndrome de Nelson/tratamento farmacológico , Ácido Valproico/uso terapêutico , Hormônio Adrenocorticotrópico/metabolismo , Aminoglutetimida/uso terapêutico , Bromocriptina/uso terapêutico , Ciproeptadina/uso terapêutico , Cetoconazol/uso terapêutico , Metirapona , Mifepristona/uso terapêutico , Mitotano/uso terapêutico , Ritanserina/uso terapêutico , Síndrome de Cushing/cirurgia , Síndrome de Cushing/radioterapia , Síndrome de Nelson/cirurgia , Síndrome de Nelson/radioterapia , Somatostatina/análogos & derivados , Tireotropina/metabolismoRESUMO
Los adenocarcinomas de la corteza suprarrenal son entidades clínicas muy poco comunes que alcanzan una frecuencia de 0.2 por ciento entre todas las neoplasias. Por lo regular, la mayoría de ellas son de tipo funcionante y tienen una presentación clínica que va a depender del exceso circulante de la hormona producida por cualquiera de las tres capas que componen la estructura cortical. Sin embargo, un mínimo porcentaje de estas neoplasias se consideran no funcionantes siendo, por su forma de presentación, todo un reto diagnóstico para el clínico. El objetivo del presente trabajo es informar el caso de un paciente masculino en la séptima década de la vida con pérdida de peso, masa suprarrenal derecha y otra en mesogastrio con determinación de 17 cetoesteroides, cortisol plasmático y ácido vainillilmandélico normales y en quien la necropsia mostró adenocarcinoma de corteza suprarrenal. Se realiza revisión de la literatura enfocada al diagnóstico y tratamiento
Assuntos
Pessoa de Meia-Idade , Humanos , Masculino , Pneumonia Pneumocócica/fisiopatologia , Enfisema Pulmonar/fisiopatologia , Esclerose/fisiopatologia , Hidrocortisona/metabolismo , Adenocarcinoma/fisiopatologia , Neoplasias do Córtex Suprarrenal/fisiopatologia , Aminoglutetimida/uso terapêutico , Cetoconazol/uso terapêutico , Mitotano/uso terapêutico , Androgênios/metabolismo , Estrogênios/metabolismoRESUMO
En el presente estudio se presenta una revision condensada sobre el concepto actual de los dos tipos conocidos de asma: 1) extrinseca o alergica, y 2) intrinseca o idiosincrasica, ademas de los resultados en la utilizacion del farmaco mititane (o,p-DDD) como un nuevo medicamento homeopatico en el tratamiento des asma, la justificacion para su uso, su tecnica de preparacion y la casuistica de 120 pacientes de la consulta particular en el periodo de los ultimos 3 años
Assuntos
Asma/terapia , Mitotano/uso terapêutico , DDT , Medicamentos Homeopáticos NovosRESUMO
En el presente estudio se presenta una revision condensada sobre el concepto actual de los dos tipos conocidos de asma: 1) extrinseca o alergica, y 2) intrinseca o idiosincrasica, ademas de los resultados en la utilizacion del farmaco mititane (o,p-DDD) como un nuevo medicamento homeopatico en el tratamiento des asma, la justificacion para su uso, su tecnica de preparacion y la casuistica de 120 pacientes de la consulta particular en el periodo de los ultimos 3 anos
Assuntos
Mitotano/uso terapêutico , Asma/terapia , Medicamentos Homeopáticos Novos , DDTRESUMO
Os autores estudaram 24 casos de carcinoma funcionante do cørtex adrenal com o objetivo de revisar o tratamento cir£rgico e quimioter pico. Procurou-se fazer correlaüoes com o tipo de cirurgia e a efi cia da quimioterapia com a sobrevida. Observou-se que tanto a adrenalectomia como a nefroadrenalectomia ofereceram resultados semelhantes em termos de sobrevida e significativamente a sobrevida. (Arq Bras Endocrinol Metab 1994; 38/1:16-22).