Severe hypercortisolism is characterized as a life-threatening endocrine condition in patients with Cushing syndrome, usually related to the concomitant onset of one or more comorbidities, requiring rapid normalization of cortisol concentrations and aggressive treatment of associated complications. It is mainly, but not exclusively, caused by ectopic ACTH syndrome, and the diagnosis of severity is more accurate when is based on simultaneous evaluation of the clinical course and manifestations of the disease, cortisol levels and systematic search of comorbidities. Once the severity and imminent risk to life are established, urgent therapeutic measures must be taken and etiological investigation postponed until the patient is stabilized. Adrenal steroidogenesis inhibitors (mainly etomidate, ketoconazole, and metyrapone), alone or in combined therapy, are commonly the first-line treatment for severe hypercortisolemia due to their rapid action, good efficacy and safety profile. The new drug osilodrostat is a future potential candidate to be included in the list. The glucocorticoid receptor antagonist mifepristone has also a rapid action, but its use has been limited due to difficulties to monitor its efficacy and safety. Other slow-acting cortisol-lowering drugs (mainly mitotane, cabergoline, and pasireotide) might be included in the therapeutic scheme to synergize and overcome a possible escape phenomenon frequently observed with the fast-acting drugs in the prolonged follow-up. When medical therapies fail, are unavailable or contra-indicated, bilateral adrenalectomy should be indicated as a life-saving measure. Adrenal arterial embolization is rarely encountered in routine clinical practice, being a last alternative in specialized centers when all other options fail or are contra-indicated.

严重皮质醇增多症的特征是库欣综合征患者危及生命的内分泌疾病，通常与一种或多种合并症的同时发生有关，需要皮质醇浓度迅速恢复正常并积极治疗相关并发症。它主要（但不完全）由异位 ACTH 综合征引起，当同时评估临床病程和疾病表现、皮质醇水平和合并症的系统搜索时，严重程度的诊断更准确。一旦确定病情严重程度和迫在眉睫的生命危险，就必须采取紧急治疗措施，并推迟病因调查，直到患者病情稳定。肾上腺类固醇生成抑制剂（主要是依托咪酯、酮康唑和美替拉酮），单独或联合治疗，由于其快速起效、良好的疗效和安全性，它们通常是严重高皮质醇血症的一线治疗方法。新药 osilodrostat 是未来被列入名单的潜在候选药物。糖皮质激素受体拮抗剂米非司酮也具有快速作用，但由于难以监测其有效性和安全性，其使用受到限制。其他缓效降低皮质醇的药物（主要是米托坦、卡麦角林和帕瑞肽）可能包含在治疗方案中，以协同和克服在长期随访中经常观察到的速效药物可能出现的逃逸现象。当药物治疗失败、不可用或有禁忌症时，应将双侧肾上腺切除术作为挽救生命的措施。肾上腺动脉栓塞在常规临床实践中很少遇到，