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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 1062-1067. doi: 10.19723/j.issn.1671-167X.2023.06.017

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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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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

CLC Number: 

  • R586.2

Table 1

Characteristics of adrenocorticotropic hormone independent CS and nonfunctional adrenal mass groups"

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

Table 2

Comparison of thrombosis incidence and coagulation function between adrenocorticotropic hormone independent CS and nonfunctional adrenal mass groups"

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

Table 3

Comparison of coagulation function in different histopathologic subgroups of adrenocorticotropic hormone independent CS"

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

Table 4

Risk factors of coagulation dysfunction in adrenocorticotropic hormone independent CS patients"

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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