Correlation Between Coagulation Index and Hormone Levels in Patients with ACTH-Independent Cushing's Syndrome

Abstract

The aim of the study was to explore the relationship between hormone levels and coagulation indicators in patients with Cushing’s syndrome, providing insights into disease progression and treatment. We recruited 640 patients diagnosed with ACTH-independent Cushing’s syndrome with adrenocortical tumors, conducting comprehensive physical and laboratory examinations, and analyzing data using logistic regression models. We found that compound F at 8 AM (F8AM) and ACTH had better correlation with coagulation characteristics. We revealed negative association between F8AM levels and PLT or APTT, while ACTH exhibited opposite trends. With F8AM increasing, Fbg declined significantly, while ACTH had the opposite association. In patients with Cushing’s syndrome, chronic cortisol elevations may lead to consumptive coagulopathy, characterized by decreased PLT and Fbg levels, apart from the hypercoagulable state implied by decreased APTT.

Keywords

ACTH-independent Cushing’s syndrome - coagulation - consumptive coagulopathy

• References

• 1 Barnett R. Cushing’s syndrome. Lancet 2016; 388: 649
• 2 Trementino L, Arnaldi G, Appolloni G. et al. Coagulopathy in Cushing’s syndrome. Neuroendocrinology 2010; 92: 55-59
• 3 Lacroix A, Feelders RA, Stratakis CA. et al. Cushing’s syndrome. Lancet 2015; 386: 913-927
• 4 Sato Y, Maekawa S, Ishii R. et al. Recurrent somatic mutations underlie corticotropin-independent Cushing’s syndrome. Science 2014; 344: 917-920
• 5 Huang W, Ma X, Liang H. et al. Dietary magnesium intake affects the association between serum vitamin D and type 2 diabetes: a cross-sectional study. Front Nutr 2021; 8: 763076
• 6 Erem C, Nuhoglu I, Yilmaz M. et al. Blood coagulation and fibrinolysis in patients with Cushing’s syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest 2009; 32: 169-174
• 7 Manetti L, Bogazzi F, Giovannetti C. et al. Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing’s syndrome: results from a prospective study before and after surgery. Eur J Endocrinol 2010; 163: 783-791
• 8 Feelders RA, Nieman LK. Hypercoagulability in Cushing’s syndrome: incidence, pathogenesis and need for thromboprophylaxis protocols. Pituitary 2022; 25: 746-749
• 9 Kaptoge S, Di Angelantonio E, Pennells L. et al. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med 2012; 367: 1310-1320
• 10 Popescu NI, Lupu C, Lupu F. Disseminated intravascular coagulation and its immune mechanisms. Blood 2022; 139: 1973-1986
• 11 Van Zaane B, Nur E, Squizzato A. et al. Hypercoagulable state in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab 2009; 94: 2743-2750
• 12 Moraes LA, Paul-Clark MJ, Rickman A. et al. Ligand-specific glucocorticoid receptor activation in human platelets. Blood 2005; 106: 4167-4175
• 13 Casella S, Giudice E, Giannetto C. et al. Effects of hydrocortisone and aminophylline on the aggregation of equine platelets in vitro. J Vet Sci 2011; 12: 215
• 14 Unsworth AJ, Flora GD, Gibbins JM. Non-genomic effects of nuclear receptors: insights from the anucleate platelet. Cardiovasc Res 2018; 114: 645-655