Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study

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 $\text{value}<18$  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 ( $\text{odds}\text{ratio}\left(\text{OR}\right)=0.99$ , 95% confidence interval (CI) 0.98–0.99; $P=0.020$ ) and megestrol acetate use ( $\text{OR}=2.63$ , 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 ( $\text{OR}=2.54$ , 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.