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Higher glucocorticoid replacement doses are associated with increased mortality in patients with pituitary adenoma

Journal article
Authors Casper Hammarstrand
Oskar Ragnarsson
T. Hallén
Eva Andersson
T. Skoglund
Anna G Nilsson
Gudmundur Johannsson
Daniel S Olsson
Published in European Journal of Endocrinology
Volume 177
Issue 3
Pages 251-256
ISSN 1479-683X
Publication year 2017
Published at Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 251-256
Language en
Links doi.org/10.1530/EJE-17-0340
Keywords glucocorticoid, adenoma, adult, aged, cohort analysis, dose response, epidemiology, female, follow up, human, male, middle aged, mortality, Pituitary Neoplasms, register, Sweden, trends, Cohort Studies, Dose-Response Relationship, Drug, Follow-Up Studies, Glucocorticoids, Humans, Registries
Subject categories Endocrinology and Diabetes

Abstract

OBJECTIVE: Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA). METHODS: Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality. RESULTS: The analysis included 392 patients (140 women) with NFPA. Mean ± s.d. age at diagnosis was 58.7 ± 14.6 years and mean follow-up was 12.7 ± 7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20 ± 6 mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68-1.12) and 0.87 (0.63-1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20 mg (1.42 (0.88-2.17)) than that in patients with a daily HCeq dose of 20 mg (0.71 (0.49-0.99)), P = 0.017. In a Cox-regression analysis, a daily HCeq dose of >20 mg was independently associated with a higher mortality (HR: 1.88 (1.06-3.33)). Patients with daily HCeq doses of ≤20 mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population. CONCLUSION: Patients with NFPA and AI receiving more than 20 mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20 mg HCeq per day or less is not increased. © 2017 European Society of Endocrinology.

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