Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Aurora Research Institute and Departments of Medicine, Surgery, and Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Compr Physiol. 2014 Apr;4(2):739-69. doi: 10.1002/cphy.c130035.
The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing's syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing's syndrome). Endogenous Cushing's syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing's syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control.
下丘脑-垂体-肾上腺（HPA）轴是经典的神经内分泌系统。了解 HPA 轴的最佳方法之一是了解其在影响 HPA 轴的各种疾病和综合征中的动态。糖皮质激素活性过多可能是由于内源性皮质醇过度产生（自发性库欣综合征）或外源性糖皮质激素治疗（医源性库欣综合征）所致。内源性库欣综合征可细分为 ACTH 依赖性和 ACTH 非依赖性，后者通常是由于肾上腺自主性过度产生。前者可能是由于垂体促肾上腺皮质激素细胞瘤（通常为良性）或垂体外异位 ACTH 产生所致；这两种肿瘤类型都过度表达前阿黑皮素原基因。库欣综合征的相反情况是正常皮质醇分泌缺乏，通常是由于肾上腺破坏（原发性肾上腺功能不全）或垂体功能减退症（继发性肾上腺功能不全）所致。继发性肾上腺功能不全也可能由于 HPA 轴抑制和肾上腺萎缩导致长期、药物性糖皮质激素治疗的快速停药而导致。最后，肾上腺皮质甾体生成酶的突变可导致先天性肾上腺增生和前体类固醇（尤其是雄激素）增加。如果在子宫内存在，这可能导致女性胎儿的男性化。了解 HPA 轴的动力学对于掌握垂体-肾上腺疾病的诊断和鉴别诊断是必要的。此外，了解 HPA 轴的病理生理学可以深入了解其正常控制。
