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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (6): 1062-1067. doi: 10.19723/j.issn.1671-167X.2023.06.017

• 论著 • 上一篇    下一篇

肾上腺性库欣综合征与无功能腺瘤患者的凝血功能比较及其影响因素

王薇1,王佳宁1,2,虞巍3,朱赛楠4,高莹1,*(),张俊清1   

  1. 1. 北京大学第一医院内分泌科, 北京 100034
    2. 北京市隆福医院内分泌科, 北京 100010
    3. 北京大学第一医院泌尿外科, 北京 100034
    4. 北京大学第一医院医学统计室, 北京 100034
  • 收稿日期:2021-10-21 出版日期:2023-12-18 发布日期:2023-12-11
  • 通讯作者: 高莹 E-mail:gaoyingpkufh@bjmu.edu.cn
  • 基金资助:
    中央高水平医院临床科研业务费及北京大学第一医院临床研究青年基金(2019CR22)

Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors

Wei WANG1,Jia-ning WANG1,2,Wei YU3,Sai-nan ZHU4,Ying GAO1,*(),Jun-qing ZHANG1   

  1. 1. Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
    2. Department of Endocrino-logy, Beijing Longfu Hospital, Beijing 100010, China
    3. Department of Urology, Peking University First Hospital, Beijing 100034, China
    4. Department of Medical Statistics, Peking University First Hospital, Beijing 100034, China
  • Received:2021-10-21 Online:2023-12-18 Published:2023-12-11
  • Contact: Ying GAO E-mail:gaoyingpkufh@bjmu.edu.cn
  • Supported by:
    National High Level Hospital Clinical Research Funding and Youth Clinical Research Project of Peking University First Hospital(2019CR22)

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摘要：

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。

关键词: 库欣综合征, 非促肾上腺皮质激素依赖性, 血液凝固, 皮质醇, 糖化血红蛋白

Abstract:

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.

Key words: Cushing syndrome, Adrenocorticotropic hormone independent, Blood coagulation, Cortisol, Glycated hemoglobin

中图分类号: 

  • R586.2

表1

肾上腺性CS与肾上腺无功能腺瘤患者一般情况比较"

Items CS (n=171) Nonfunctional adrenal mass (n=171) P value
Male 57 (33.33) 57 (33.33)
Age/years 47.16±13.80 54.18±11.15 < 0.001
BMI/(kg/m2) 26.0±3.8 26.1±3.7 0.797
Hypertension 139 (81.3) 111 (64.9) 0.001
Diabetes 59 (34.5) 48 (28.1) 0.200
SBP/mmHg 144.3±18.8 138.2±18.0 0.002
DBP/mmHg 88.1±14.8 80.1±12.6 < 0.001
HbA1c/% 6.4±1.1 6.4±1.3 0.870
FPG/(mmol/L) 5.8±2.1 5.9±1.8 0.688
Plasma K+/(mmol/L) 3.54±0.44 3.72±0.34 < 0.001
TG/(mmol/L) 1.66±0.81 1.74±1.12 0.454
TCHO/(mmol/L) 5.00±1.17 4.57±0.98 < 0.001
LDL-C/(mmol/L) 3.04±0.85 2.71±0.74 < 0.001
Neutrophil count/(×109/L) 5.26±2.14 4.01±1.32 < 0.001
NLR 3.45(2.44，5.60) 2.14(1.76，3.00) < 0.001
8:00 serum cortisol/(μg/dL) 17.18 (12.53, 24.46) 12.35 (9.72, 16.88) < 0.001
16:00 serum cortisol/(μg/dL) 13.92 (9.28, 21.62) 6.63 (5.05, 9.48) < 0.001
24:00 serum cortisol/(μg/dL) 12.42 (7.07, 19.64) 2.60 (1.76, 4.51) < 0.001
Serum cortisol AUC/[(μg/dL)·h] 341.4 (242.6，521.1) 188.9 (150.9，233.2) < 0.001
8:00 ACTH/(ng/L) 1.78 (0.99, 5.79) 18.46 (12.30, 26.61) < 0.001
16:00 ACTH/(ng/L) 1.52 (0.99, 4.04) 10.12 (7.31, 16.13) < 0.001
24:00 ACTH/(ng/L) 1.20 (0.99, 2.63) 6.90 (3.86, 11.62) < 0.001
24 h urine cortisol/(μg/24 h) 1 034.4 (588.1, 1 929.3) 545.4 (413.8, 719.5) < 0.001

表2

肾上腺性CS组与无功能腺瘤组血栓事件及凝血功能的比较"

Items CS (n=171) Nonfunctional adrenal mass (n=171) P value
DVT 3 (1.75) 0 0.082
PE 1 (0.58) 0 0.317
PT/s 10.67±1.08 10.96±0.84 0.008
INR 1.02±0.10 1.02±0.10 0.396
APTT/s 29.22±3.39 31.86±3.63 < 0.001
FIB/(g/L) 2.85±0.61 2.97±0.58 0.055
D-dimer/(mg/L) 0.09 (0.05, 0.16) 0.07 (0.04, 0.11) 0.013
FDP/(mg/L) 1.2 (0.6, 2.0) 0.9 (0.5, 1.7) 0.041
TT/s 14.20±1.51 14.40±1.06 0.168
Platelet count/(×109/L) 231.0±59.4 224.9±52.7 0.312

表3

肾上腺性CS患者中不同病理类型亚组间凝血功能相关指标的比较"

Items Adrenocortical adenoma (n=82) Adrenocortical hyperplasia (n=11) Oncocytic adenoma (n=35) Adrenocortical carcinoma (n=5) P
PT/s 10.65±0.85 10.28±0.82 10.84±1.84 10.78±0.68 0.637
APTT/s 28.90±3.75 28.63±2.53 28.62±3.17 29.18±1.99 0.972
FIB/(g/L) 2.80±0.69 2.84±0.51 2.87±0.55 2.96±0.73 0.920
D-dimer/(mg/L) 0.09 (0.04, 0.15) 0.11 (0.05, 0.28) 0.09 (0.05, 0.20) 0.14 (0.08, 0.31) 0.663
FDP/(mg/L) 1.2 (0.6, 2.0) 1.3 (0.2, 2.4) 1.3 (0.5, 2.1) 2.9 (1.5, 4.6) 0.151
TT/s 14.32±1.15 14.33±2.54 13.62±2.24 14.38±1.04 0.266

表4

肾上腺性CS患者发生凝血功能异常的危险因素"

Risk factors β OR (95% CI) P value
Serum cortisol AUC 0.488 1.63 (1.09, 2.43) 0.017
24 h urine cortisol -0.027 0.97 (0.92, 1.03) 0.315
HbA1c 0.484 1.62 (1.06, 2.48) 0.025
Neutrophil count 0.179 1.20 (0.88, 1.64) 0.262
NLR -0.041 0.96 (0.80，1.15) 0.664
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ISSN 1671-167X
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