内源性库欣综合征(CS)是一种罕见的,由垂体腺瘤持续的慢性糖皮质激素过量引起的多系统病症(库欣病,CD),肾上腺腺瘤或,不那么频繁,神经内分泌肿瘤.最佳的一线选择是手术,但是当它被禁忌/拒绝时,或者在严重的情况下,危及生命的疾病,医疗是一线选择。Osilodrostat(LCI699,Isturisa®)是一种新的,目前FDA和EMA批准的口服活性肾上腺类固醇生成抑制剂用于治疗内源性CS。
我们说明了osilodrostat的药理学概况,并总结了从第一阶段研究到最新证据的osilodrostat的疗效和安全性。
Osilodrostat作为一种有效的,11β-羟化酶(CYP11B1)和18-羟化酶(或醛固酮合酶,CYP11B2),同时抵消葡萄糖和盐皮质激素的产生。根据LINC1,LINC2和LINC3研究的结果以及LINC4的初步发现,osilodrostat在控制皮质醇增多症中具有良好的耐受性。肾上腺功能不全/类固醇戒断症状的不可忽视的风险,低钾血症,和高雄激素血症,和可能性,虽然罕见,垂体瘤增大,需要进一步确认和仔细监测。
Endogenous Cushing\'s syndrome (CS) is a rare, multi-systemic condition resulting from chronic glucocorticoid excess sustained by a pituitary adenoma (Cushing\'s disease, CD), an adrenal adenoma or, less frequently, a neuroendocrine tumor. The optimal first-line option is surgery, but when it is contraindicated/refused, or in case of severe, life-threatening disease, medical treatment is a first-line choice. Osilodrostat (LCI699, Isturisa®) is a new, orally active adrenal steroidogenesis inhibitor currently approved by the FDA and EMA for the treatment of endogenous CS.
We illustrate the pharmacologic profile of osilodrostat and summarize the efficacy and safety of osilodrostat from the first phase I studies to the most recent evidence.
Osilodrostat acts as a potent, reversible inhibitor of 11β-hydroxylase (CYP11B1) and 18-hydroxylase (or aldosterone synthase, CYP11B2), counteracting both gluco- and mineralocorticoid production. According to the results of the LINC1, LINC2, and LINC3 studies and the preliminary findings of LINC4, osilodrostat offers an excellent efficacy in controlling hypercortisolism with a good tolerability. The non-negligible risk of adrenal insufficiency/steroid withdrawal symptoms, hypokalemia, and hyperandrogenism disorders, and the possibility, albeit rare, of pituitary tumor enlargement, require further confirmation and careful monitoring.