Inadequately Regulated Adrenal Steroids through HPA Axis In Chronic Idiopathic Thrombocytopenic Purpura

Abstract 5130

Idiopathic thrombocytopenic purpura (ITP) is an immune disorder along with the condition of having a low platelet count of multiple etiologies. Endogenous steroids such as corticosteroids have been known to have potent immunomodulatory effect, and also altered expression of steroid metabolism have been reported on the immune related diseases. The level of endogenous steroids are closely related with the level of cytokines (IL-6, IL-1, TNF-α) through HPA axis. Therefore, the eluciadaton of the relationship between steroid hormones and immune cytokines through hypothalamic-pituitary-adrenal (HPA) axis may help to identify biochemical roles of steroid hormones in ITP. The metabolites of steroid hormones were assayed in the plasma obtained from 54 ITP patients and 44 controls using the validated GC-MS based signatures of 70 endogenous steroids including 22 androgens, 18 estrogens, 15 corticoids, 13 progestin, 2 sterols. We also measured the plasma concentration of three HPA axis-stimulating cytokines (IL-6, IL-1, TNF-α) and adrenocorticotropic hormone (ACTH) in chronic ITP patients and healthy subjects using Luminex xMAP technology. Patients were classified to active and remission state depending on the platelet count (active, less than 50,000/mm³; remission, over 100,000/mm³). The active ITP patients showed significant lower plasma levels of adrenal steroids such as pregnenolone (1.49 ± 0.71 ng/mL vs 3.07 ± 1.30 ng/mL, p = 2.3E–08), dehydroepiandrosterone (2.98 ± 1.57 ng/mL vs 4.82 ± 1.67 ng/mL, p = 7.1E-05) and cortisol (73.8 ± 11.3 ng/mL vs 112.7 ± 30.1 ng/mL, p = 2.6E–10) compared with healthy subjects, while the levels of adrenal steroids in remission ITP patients (pregnenolone, 1.87 ± 0.76 ng/mL; dehydroepiandrosterone, 3.70 ± 1.95 ng/mL, cortisol, 83.2 ± 16.2 ng/mL) were not recovered to normal levels. The cortisol/ACTH (ng/mL vs pg/mL) ratio representing pituitary-adrenal axis was not significantly different between patients (4.63 ± 0.72) and healthy subjects (5.17 ± 0.67). However, there was a positive correlation between ACTH and IL-6 in healthy subjects (R = 0.672, p = 0.0024), while no correlation in ITP patients. In conclusion, the low levels of endogenous adrenal steroids resulted from dysregulated HPA axis may have a role in the pathogenesis of ITP.