Abstract
Data on the rate of adrenal insufficiency (AI) in patients receiving short-course and high-dose corticosteroids are limited. In this study, we aimed to determine the incidence of AI in newly diagnosed, diffuse large B cell lymphoma (DLBCL) patients after receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [or prednisolone] (R-CHOP/CHOP) regimen. We enrolled newly diagnosed DLBCL patients who were scheduled to receive 6–8 cycles of R-CHOP/CHOP regimen. One-microgram adrenocorticotropic hormone (ACTH) stimulation tests were performed at the study entry and 3 weeks after each cycle of chemotherapy (CMT). AI was defined by a peak-stimulated serum cortisol of less than 18 μg/dL. For patients who had AI after completing a course of CMT, 1-μg ACTH stimulation tests were carried out at 60 and 90 days after the last CMT cycle to assess the duration of hypothalamic-pituitary-adrenal (HPA) axis recovery. Ten DLBCL patients were included in this study, with a total of 84 1-μg ACTH stimulation tests. Their mean age was 52 years. AI occurred in 3 out of the 10 patients (30%). The first occurrence of AI was after the third CMT cycle, and the incidence was highest after the fifth cycle. Adrenal function recovered completely 3 to 5 weeks after completing the course of CMT, except for 1 patient, whose HPA axis suppression persisted 90 days after the last CMT cycle. Receiver operating characteristic (ROC) analysis revealed that a basal cortisol level of < 8.7 μg/dL was predictive of AI, with a sensitivity and specificity of 80% and 72.2%, respectively. Transient HPA axis suppression can occur in DLBCL patients receiving R-CHOP/CHOP regimen. We strongly encourage careful observation and examination for potential adrenal insufficiency in such patients, particularly after the fifth cycle of chemotherapy.
Highlights
Secondary adrenal insufficiency (AI) is an adrenal hypofunction caused by inadequate levels of adrenocorticotropic hormone (ACTH) being produced by the pituitary gland
We found that the first occurrence of AI was after the third chemotherapy cycle, and the highest incidence was after the fifth cycle (p = 0.008; Fig. 2)
The area under the Receiver operating characteristic (ROC) curve (AUC) to predict adrenal insufficiency showed that the AUC for basal cortisol of < 8.7 μg/dL was 0.77, whereas those of ACTH ≥ 26.4 pg/mL and ACTH/cortisol ratio ≥ 3.3 were 0.63 and 0.75, respectively (Table 3)
Summary
Secondary adrenal insufficiency (AI) is an adrenal hypofunction caused by inadequate levels of adrenocorticotropic hormone (ACTH) being produced by the pituitary gland. The most common cause of secondary AI is chronic exogenous steroid use, and it has been observed to have diverse routes of administration, Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand. Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand including systemic, topical, intra-articular, inhaled, and ocular [1,2,3,4,5]. The occurrence and duration of the hypothalamicpituitary-adrenal axis (HPA) suppression depend on the duration and dosage of the exogenous steroids. Data on the duration of the HPA axis suppression are lacking
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