Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
Trends Endocrinol Metab. 2015 Oct;26(10):573-583. doi: 10.1016/j.tem.2015.08.003.
Cushing's disease (CD) is caused by corticotropin-secreting pituitary adenomas and results in substantial morbidity and mortality. Its molecular basis has remained poorly understood until the past few years, when several proteins and genes [such as testicular orphan nuclear receptor 4 (TR4) and heat shock protein 90 (HSP90)] were found to play key roles in the disease. Most recently, mutations in the gene of ubiquitin-specific peptidase 8 (USP8) increasing its deubiquination activity were discovered in a high percentage of corticotroph adenomas. Here, we will discuss emerging insights in the molecular alterations that finally result in CD. The therapeutic potential of these findings needs to be carefully evaluated in the near future, hopefully resulting in new treatment options for this devastating disorder.
库欣病（CD）是由促肾上腺皮质激素分泌垂体腺瘤引起的，可导致严重的发病率和死亡率。直到过去几年，当发现几种蛋白质和基因[如睾丸孤儿核受体 4（TR4）和热休克蛋白 90（HSP90）]在疾病中发挥关键作用时，其分子基础仍未得到很好的理解。最近，在大多数促肾上腺皮质激素腺瘤中发现了泛素特异性肽酶 8（USP8）基因的突变，增加了其去泛素化活性。在这里，我们将讨论最终导致 CD 的分子改变的新见解。这些发现的治疗潜力需要在不久的将来进行仔细评估，希望为这种破坏性疾病带来新的治疗选择。
