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Secondary Adrenal Insufficiency: A Cross-sectional Study of Nasopharyngeal Carcinoma Patients after Treatment with Intensity-modulated Radiotherapy

Objective: To review the incidence of secondary adrenal insufficiency (SAI) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT), and to determine the characteristics and risk factors associated with the development of SAI. Methods: A total of 143 NPC patients diagnosed between 2009 and 2010 and treated with radical IMRT were retrospectively reviewed. The low-dose short Synacthen test was used to determine the presence of SAI. Using Kaplan-Meier method and Cox proportional hazard regression, the relationship between development of SAI and various clinical parameters was evaluated. Results: The median follow-up period was 65 months. The median mean and median maximum doses to the pituitary gland were 56.3 Gy (range, 19.1-72.0 Gy) and 59.5 Gy (range, 28.5-73.8 Gy), respectively. The cumulative incidences of SAI at 2 and 5 years post-treatment were 7.7% and 17.5%, respectively. The median time to onset of SAI was 30.5 (range, 16-82) months after radiotherapy. Multiple Cox regression analysis revealed that receiving additional radiotherapy after a definitive course of radiotherapy was an independent risk factor for the development of SAI, with a relative risk of 6.598 (95% confidence interval = 1.554-28.013; p = 0.01). Conclusion: SAI is common in NPC patients treated with IMRT. Regular monitoring of hypothalamic-pituitary– adrenal axis hormone function should start as early as 6 months to 1 year post-treatment so that treatment can be initiated early if indicated, especially in patients who have received additional radiotherapy after definitive radiotherapy for NPC.