Coiro V, Volpi R, Galli P, Manfredi G, Magotti M G, Saccani-Jotti G, Chiodera P
Department of Internal Medicine and Biomedical Sciences, University of Parma, Parma, Italy.
Horm Res. 2004;61(3):148-52. doi: 10.1159/000075671. Epub 2003 Dec 18.
The distinction between Cushing's disease (Cushing's syndrome dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary origin) and pseudo-Cushing's states (Cushingoid features and hypercortisolism sometimes present in alcoholic, depressed or obese subjects) can present a diagnostic challenge in clinical endocrinology. Recently, the availability of a highly sensitive immunofluorometric assay for the measurement of total prostate-specific antigen (PSA) provided the possibility to measure serum PSA levels in women. Interestingly, PSA gene expression and protein production has been found to be upregulated by steroid hormones, such as androgens, glucocorticoids, mineral corticoids and progestins. In fact, serum total PSA concentrations appear to be higher in female patients with Cushing's disease than in normal women. We wondered whether a similar phenomenon also occurs in pseudo-Cushing's state.
In order to answer this question, we compared the serum total PSA levels measured in 10 female subjects with alcohol-dependent pseudo-Cushing's state with those observed in 8 female patients with Cushing's disease and in 15 age-matched healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary cortisol levels were measured; cortisol suppression after dexamethasone was also tested in all subjects.
The basal serum levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing's disease or pseudo-Cushing's state; these latter groups showed similar basal hormonal values. Dexamethasone administration was unable to suppress serum cortisol levels in 5 subjects with Cushing's disease and 6 subjects with pseudo-Cushing's state. Serum testosterone values in the group with Cushing's disease were higher than in the other groups. No differences were observed between pseudo-Cushing's and normal subjects. Serum total PSA levels were significantly higher in women with Cushing's disease than in subjects with pseudo-Cushing's state and normal controls; these latter groups showed similar PSA values. When serum total PSA and testosterone levels were considered together, a significant positive correlation was observed in the group with Cushing's disease, but not in the other groups.
These data indicate that the steroid milieu responsible for the elevation in serum PSA in women with Cushing's disease is not present in subjects with alcohol-dependent pseudo-Cushing's state, suggesting the possible use of PSA as a marker of differentiation between these pathological conditions in women.
库欣病（依赖垂体来源的促肾上腺皮质激素（ACTH）分泌肿瘤的库欣综合征）与假性库欣状态（酒精性、抑郁或肥胖患者中有时出现的库欣样特征和皮质醇增多症）之间的鉴别在临床内分泌学中可能是一项诊断挑战。最近，一种用于测量总前列腺特异性抗原（PSA）的高灵敏度免疫荧光测定法使得测量女性血清PSA水平成为可能。有趣的是，已发现PSA基因表达和蛋白质产生会被雄激素、糖皮质激素、盐皮质激素和孕激素等类固醇激素上调。事实上，库欣病女性患者的血清总PSA浓度似乎高于正常女性。我们想知道类似的现象在假性库欣状态中是否也会发生。
为了回答这个问题，我们比较了10名酒精依赖型假性库欣状态女性受试者、8名库欣病女性患者和15名年龄匹配的健康女性的血清总PSA水平。测量了血清睾酮、ACTH和皮质醇以及24小时尿皮质醇水平；还对所有受试者进行了地塞米松后的皮质醇抑制试验。
正常受试者的基础血清ACTH和皮质醇水平显著低于库欣病或假性库欣状态患者；后两组的基础激素值相似。地塞米松给药无法抑制5名库欣病患者和6名假性库欣状态患者的血清皮质醇水平。库欣病组的血清睾酮值高于其他组。假性库欣状态患者与正常受试者之间未观察到差异。库欣病女性患者的血清总PSA水平显著高于假性库欣状态患者和正常对照组；后两组的PSA值相似。当同时考虑血清总PSA和睾酮水平时，库欣病组观察到显著的正相关，而其他组未观察到。
这些数据表明，酒精依赖型假性库欣状态患者不存在导致库欣病女性血清PSA升高的类固醇环境，提示PSA可能用作女性这些病理状况之间鉴别的标志物。
