Abstract：
Cushing\'s syndrome is characterized by chronic glucocorticoid oversecretion and diverse clinical manifestations. Distinguishing between adrenocorticotropic hormone (ACTH)-independent and ACTH-dependent forms is crucial for determining treatment options. Plasma ACTH levels aid in the differential diagnosis, with undetectable or low levels suggesting ACTH-independent hypercortisolemia. ACTH is derived from pro-opiomelanocortin, and its processing involves prohormone convertase 1/3. High-molecular-weight ACTH is generally found in ACTH-producing pituitary tumors and ectopic ACTH syndrome. The mechanism of negative feedback and the process of high-molecular-weight ACTH alternation during ACTH-independent Cushing\'s syndrome remain unclear. A 40-year-old woman with hypertension and multiple fractures developed symptoms suggestive of Cushing\'s syndrome. Computed tomography revealed a left adrenocortical tumor along with atrophy of the right adrenal gland. ACTH levels were undetectable at the previous clinic, indicating ACTH-independent Cushing\'s syndrome. However, subsequent measurements at our hospital revealed non-suppressed ACTH (18.1 pg/mL), prompting further investigation. Gel exclusion chromatography confirmed the presence of high-molecular-weight ACTH. Metyrapone treatment decreased the cortisol levels. In this situation, in which ACTH levels should be elevated, a decrease in high-molecular-weight ACTH levels was observed. Histological findings revealed cortisol-producing adenoma without ACTH expression. This case highlights the importance of assay differences in evaluating ACTH concentrations and introduces a novel finding of circulating high-molecular-weight ACTH. The observed decline in high-molecular-weight ACTH levels suggests a potential time lag in the negative feedback within the hypothalamic-pituitary-adrenal axis exhibited by glucocorticoids. This temporal aspect of the regulation of ACTH-related molecules warrants further exploration to enhance our understanding of the hypothalamic-pituitary-adrenal axis feedback mechanism.
摘要：
库欣综合征以慢性糖皮质激素过度分泌为特征,临床表现多样。区分促肾上腺皮质激素（ACTH）非依赖性和ACTH依赖性形式对于确定治疗方案至关重要。血浆ACTH水平有助于鉴别诊断，检测不到或低水平提示ACTH非依赖性皮质醇血症。ACTH来自前乌黑皮质素，其加工涉及激素原转化酶1/3。高分子量ACTH通常见于产生ACTH的垂体瘤和异位ACTH综合征。ACTH非依赖性库欣综合征的负反馈机制和高分子量ACTH交替过程尚不清楚。一名40岁的高血压和多发性骨折妇女出现了提示库欣综合征的症状。计算机断层扫描显示左肾上腺皮质肿瘤以及右肾上腺萎缩。在以前的诊所检测不到ACTH水平，表明ACTH非依赖性库欣综合征。然而,在我们医院进行的后续测量显示未抑制的ACTH（18.1pg/mL），促使进一步调查。凝胶排阻层析证实了高分子量ACTH的存在。Metyrapone治疗可降低皮质醇水平。在这种情况下,其中ACTH水平应该升高，观察到高分子量ACTH水平下降.组织学发现显示产生皮质醇的腺瘤没有ACTH表达。此案例强调了测定差异在评估ACTH浓度中的重要性，并介绍了循环高分子量ACTH的新发现。观察到的高分子量ACTH水平下降表明，糖皮质激素表现出的下丘脑-垂体-肾上腺轴内的负反馈可能存在时滞。ACTH相关分子调节的时间方面值得进一步探索，以增强我们对下丘脑-垂体-肾上腺轴反馈机制的理解。
