Objective: To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).
Methods: In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.
Results: In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).
Conclusion: ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.
目的: 总结肾上腺性库欣综合征(Cushing syndrome, CS)患者凝血功能相关指标的特点, 为临床更好地识别肾上腺性CS的高凝状态, 预防并发症, 提供理论依据。
方法: 本研究为回顾性研究, 在北京大学第一医院住院电子病历系统中检索2014年1月至2019年6月出院诊断为肾上腺性CS患者的病历资料, 以体重指数、性别、出院时间匹配的肾上腺无功能腺瘤患者为对照, 比较两组患者的临床特点及凝血功能的相关指标。
结果: 肾上腺性CS组活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、凝血酶原时间(prothrombin time, PT)均较对照组显著缩短[(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001;(10.67±1.08) s vs. (10.96±0.84) s, P=0.008], D-二聚体与纤维蛋白降解产物(fibrin degradation products, FDP)水平均显著升高。血清皮质醇节律的曲线下面积与PT、APTT呈显著负相关, 与FDP、D-二聚体水平呈显著正相关。Logistic回归分析提示, 皮质醇曲线下面积增大、糖化血红蛋白升高是CS患者发生高凝的独立危险因素(P < 0.05)。
结论: 肾上腺性CS患者较无功能肾上腺腺瘤患者更易出现高凝状态, 因此, 对于肾上腺性CS患者, 尤其是高皮质醇水平及高糖化血红蛋白的患者, 需要关注其高凝状态及血栓发生的风险。
Keywords: Adrenocorticotropic hormone independent; Blood coagulation; Cortisol; Cushing syndrome; Glycated hemoglobin.