Endocrinology Unit, Department of Medicine-DIMED, University Hospital of Padova, 35128 Padova, Italy.
Department of Biology, University of Padova, 35128 Padova, Italy.
Int J Mol Sci. 2022 Jun 9;23(12):6469. doi: 10.3390/ijms23126469.
Adrenocorticotropic Hormone (ACTH)-secreting pituitary adenomas are rare tumors characterized by autonomous ACTH secretion with a consequent increase in circulating cortisol levels. The resulting clinical picture is called Cushing's disease (CD), a severe condition burdened with high morbidity and mortality. Apart from increased cortisol levels, CD patients exhibit a partial resistance to the negative glucocorticoid (GC) feedback, which is of paramount clinical utility, as the lack of suppression after dexamethasone administration is one of the mainstays for the differential diagnosis of CD. Since the glucocorticoid receptor (GR) is the main regulator of negative feedback of the hypothalamic-pituitary-adrenal axis in normal conditions, its implication in the pathophysiology of ACTH-secreting pituitary tumors is highly plausible. In this paper, we review GR function and structure and the mechanisms of GC resistance in ACTH-secreting pituitary tumors and assess the effects of the available medical therapies targeting GR on tumor growth.
促肾上腺皮质激素（ACTH）分泌性垂体腺瘤是一种罕见的肿瘤，其特征是自主分泌 ACTH，导致循环皮质醇水平升高。由此产生的临床表现称为库欣病（CD），这是一种严重的疾病，发病率和死亡率都很高。除了皮质醇水平升高外，CD 患者还表现出对负性糖皮质激素（GC）反馈的部分抵抗，这在临床上非常有用，因为地塞米松给药后缺乏抑制是 CD 鉴别诊断的主要依据之一。由于糖皮质激素受体（GR）是正常情况下下丘脑-垂体-肾上腺轴负反馈的主要调节剂，因此其在 ACTH 分泌性垂体肿瘤的病理生理学中的作用是合理的。本文综述了 GR 的功能和结构以及 ACTH 分泌性垂体肿瘤中 GC 抵抗的机制，并评估了针对 GR 的现有医学治疗方法对肿瘤生长的影响。
