Christopoulos Stavroula, Bourdeau Isabelle, Lacroix André
Division of Endocrinology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, Canada.
Horm Res. 2005;64(3):119-31. doi: 10.1159/000088818.
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a very rare cause of endogenous Cushing's syndrome (CS). In this review, the clinical characteristics, the pathophysiology, and the management of AIMAH are described. AIMAH typically presents with overt CS, but subclinical oversecretion of cortisol has been increasingly described. The diagnosis is suspected by adrenal nodular enlargement on conventional imaging following the demonstration of ACTH-independent hypercortisolism. Final diagnosis is established by histological examination of the adrenal tissue. Bilateral adrenalectomy is the treatment of choice but unilateral adrenalectomy has been proposed in selected cases. In patients with subclinical CS, the decision to treat should be individualized. The pathophysiology of this condition has begun to be elucidated in recent years. Diverse aberrant membrane-bound receptors expressed in a non-mutated form in the adrenal gland have been found to be implicated in the regulation of steroidogenesis in AIMAH. When systematically screened, most patients with AIMAH and CS or subclinical CS exhibit an in vivo aberrant cortisol response to one or various ligands suggesting the presence of aberrant adrenal receptors. A protocol designed to screen patients for the presence of these aberrant receptors should be undertaken in all patients with AIMAH. The identification of these receptors provides the potential for novel pharmacological therapies by suppressing the endogenous ligands or blocking the receptor with specific antagonists.
促肾上腺皮质激素（ACTH）非依赖性大结节性肾上腺增生（AIMAH）是内源性库欣综合征（CS）的一种非常罕见的病因。在本综述中，描述了AIMAH的临床特征、病理生理学及治疗方法。AIMAH通常表现为明显的CS，但越来越多的文献报道了其皮质醇的亚临床分泌过多。在证实存在ACTH非依赖性皮质醇增多症后，通过传统影像学检查发现肾上腺结节性增大可怀疑该病。通过肾上腺组织的组织学检查确诊。双侧肾上腺切除术是首选治疗方法，但在某些特定病例中也有人提出行单侧肾上腺切除术。对于亚临床CS患者，治疗决策应个体化。近年来，这种疾病的病理生理学已开始得到阐明。已发现肾上腺中以非突变形式表达的多种异常膜结合受体与AIMAH中类固醇生成的调节有关。系统筛查时，大多数AIMAH及CS或亚临床CS患者体内对一种或多种配体表现出异常的皮质醇反应，提示存在异常肾上腺受体。所有AIMAH患者均应采用一种旨在筛查患者是否存在这些异常受体的方案。识别这些受体为通过抑制内源性配体或用特异性拮抗剂阻断受体进行新型药物治疗提供了可能。
