HPA axis function during adjunctive high-dose dexamethasone use in chemotherapy: a prospective pilot study

Introduction: Glucocorticoid-induced adrenal insufficiency is a well-known adverse effect of glucocorticoid therapy, occurring not only with oral administration but also with intramuscular, inhaled, and other routes of administration. However, the impact of intermittent high-dose glucocorticoids used during chemotherapy on hypothalamic-pituitary-adrenal (HPA) axis function remains incompletely understood. Methods: In this prospective pilot study, 47 women with breast cancer receiving paclitaxel-based chemotherapy with dexamethasone premedication were evaluated. Morning serum cortisol and adrenocorticotropic hormone (ACTH) concentrations were measured before dexamethasone administration at baseline and prior to subsequent weekly chemotherapy cycles. Longitudinal trends in cortisol and ACTH concentrations were analyzed using ANOVA and Spearman correlation. Results: Across the entire group, morning cortisol and ACTH concentrations showed an overall downward tendency during treatment. However, no statistically significant changes were observed. The results did not demonstrate significant suppression of morning cortisol or ACTH concentrations during intermittent high-dose dexamethasone administration in this group. Discussion: These findings underline the limitations of single cortisol measurements and highlight the need for a longitudinal approach when assessing adrenal function in oncology patients. Further studies incorporating dynamic testing are required to determine the optimal method for evaluating HPA axis function during intermittent glucocorticoid exposure.