Abstract
Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98–0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48–4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41–4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.
Highlights
Corticosteroid therapy has been used in malignant diseases because of its anticancer efficacy; it is associated with numerous adverse events [1, 2]
There were no significant differences with regard to age, sex, body mass index (BMI), and prevalence of comorbidities including hypertension, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), chronic kidney disease (CKD), and thromboembolism between the no-adrenal insufficiency (AI) and AI groups
Administration of megestrol acetate is associated with an increased risk of AI
Summary
Corticosteroid therapy has been used in malignant diseases because of its anticancer efficacy; it is associated with numerous adverse events [1, 2]. Chronic corticosteroid therapy is the most common cause of adrenal insufficiency (AI), which occurs due to inhibition of the hypothalamic-pituitary-adrenal (HPA) axis through a negative feedback mechanism after discontinuation of exogenous steroids [3, 4]. Higher doses and long-term corticosteroid therapy may be risk factors for developing AI, previous reports have reported inconsistent results regarding this. Multiple myeloma (MM) is caused by the proliferation of clonal plasma cells in the bone and bone marrow being the second most common hematological malignancy. Induction therapy with alkylating agents and corticosteroids or high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation were the main treatments.
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