Glucocorticoid Replacement and Mortality in Patients with Nonfunctioning Pituitary Adenoma

Abstract

Abstract Context: Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA). Objective: Our objective was to assess whether higher glucocorticoid replacement doses are associated with increased mortality in patients with NFPA and HPA axis insufficiency. Design, Participants, and Intervention: We included 105 patients receiving glucocorticoid replacement after pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients were grouped according weight-adapted and absolute hydrocortisone (HC) replacement doses. Mortality was assessed using Kaplan-Meier methodology as well as multivariable Cox regression models. Setting: This was a retrospective analysis conducted at a tertiary referral center. Main Outcome: We evaluated overall mortality based on HC replacement doses. Results: Average age at inclusion was 58.9 ± 14.8 yr, and mean follow-up was 12.7 ± 9.4 yr. The groups did not differ according to age, follow-up time, pattern of hypopituitarism, and comorbidities. Kaplan-Meier survival probabilities differed significantly when comparing individuals with differing weight-adjusted HC dose (P = 0.001) as well as absolute HC dose (5–19, 20–29, and ≥30 mg, P = 0.009). Hazard ratios for mortality increased from 1 (0.05–0.24 mg/kg) to 2.62 (0.25–0.34 mg/kg) to 4.56 (≥0.35 mg/kg, P for trend = 0.006) and from 1 (5–19 mg) to 2.03 (20–29 mg) to 4 (≥30 mg, P for trend = 0.029), respectively. Conclusion: Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients.