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Randomized Controlled Trial
. 2025 Mar 3;8(3):e251029.
doi: 10.1001/jamanetworkopen.2025.1029.

Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

Simon Bøggild Hansen  1   2 , Anja Fenger Dreyer  3   4 , Nanna Thurmann Jørgensen  5   6 , Hajir Al-Jorani  3   4 , Lise Sofie Bislev  1   2   7 , Victor Brun Boesen  6 , Stina Willemoes Borresen  6 , Louise Lehmann Christensen  3   4 , Dorte Glintborg  3 , Ellen Margrethe Hauge  2   8 , Merete Lund Hetland  5   9 , Richard Christian Jensen  3 , Søren Andreas Just  10 , Kresten Krarup Keller  2   8 , Marianne Klose  6 , Kristina Laugesen  11   12 , Henning Locht  9 , Marie Louise Lund  6 , Jelena Stankovic  1   2 , Paul M Stewart  13 , Randi Maria Hanghøj Tei  1 , Anne Voss  14 , Ulla Feldt-Rasmussen  5   6 , Jens Otto L Jørgensen  1   2 , Marianne Skovsager Andersen  3   4
Affiliations
Randomized Controlled Trial

Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

Simon Bøggild Hansen et al. JAMA Netw Open. .

Abstract

Importance: The widespread use of glucocorticoid (GC) therapy may result in GC-induced adrenal insufficiency (GIAI), but the prevalence and clinical implications remain uncertain.

Objective: To ascertain the prevalence and symptoms of GIAI.

Design, setting, and participants: Cross-sectional multicenter study at 3 Danish hospitals. Baseline data were collected March 2021 to March 2024 from an ongoing randomized clinical trial. Participants were patients with polymyalgia rheumatica and/or giant cell arteritis who were investigated a median (IQR) of 39 (25-62) days after planned cessation of prednisolone treatment.

Exposure: Prednisolone treatment a median (IQR) of 13 (10-20) months in duration.

Main outcomes and measures: Primary outcome GIAI was defined as a stimulated plasma cortisol level less than 420 nmol/L in response to a short 250 μg corticotropin test (SST). Secondary outcomes were adrenal insufficiency symptoms assessed by the Addison disease-specific quality of life questionnaire (AddiQoL-30), body composition, and muscle function.

Results: Of 267 patients included (145 female [55%]; median [IQR] age 73 [68-78] years), 5 (1.9%; 95% CI, 0.8%-4.3%) had GIAI, whereas 75 (34%; 95% CI, 28%-41%) had symptoms compatible with adrenal insufficiency defined by an AddiQoL-30 score 85 or lower (symptomatic group). The symptomatic group had lower basal cortisol levels compared with the asymptomatic group (263 nmol/L; 95% CI, 242-283 nmol/L vs 309 nmol/L; 95% CI, 295-324 nmol/L; P < .001). Factors associated with a low AddiQoL-30 score included female sex (prevalence ratio [PR], 1.68; 95% CI, 1.13-2.51), increased body fat percentage (PR, 2.33; 95% CI, 1.21-4.50), reduced handgrip strength (PR, 2.71; 95% CI, 1.44-5.10) and low Short Physical Performance Battery score (PR, 2.78; 95% CI, 1.42-5.42).

Conclusions and relevance: This cross-sectional study of 267 patients with polymyalgia rheumatica or giant cell arteritis found a GIAI prevalence of 1.9% after cessation of prednisolone. This is much lower than previously reported and speaks against routine screening, which should be restricted to patients with overt symptoms. The high prevalence of symptoms of adrenal insufficiency in association with lower basal cortisol levels substantiate the clinical challenges of steroid withdrawal and merit future research.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Borresen reported receiving grants from the Eva Maduras Foundation, Skibsredder R. Henriksen, and the Hustrus Foundation outside the submitted work. Dr Hauge reported receiving grants paid to institution from Novo Nordic, Independent Research Fund Denmark, Danish Rheumatism Association, Danish Regions Medicine Grant, Galapagos, AbbVie, Roche, and Novartis; receiving personal fees from Novo Nordic, Novartis, SynACT Pharma, AbbVie, Sanofi, Sobi, MSD, and USB; nonfinancial support from Celgene, Sobi, AbbVie, Novartis, Boehringer Ingelheim, Roche, and Pfizer; serving as a trial investiagor for SynACT Pharma, AbbVie, Novartis, Novo Nordic, and Sanofi. Dr Hetland reported receiving grants paid to institution from AbbVie, AlfaSigma, BMS, Eli Lilly, MSD, Pfizer, Sandoz, Novartis, Nordforsk, and UCB; receiving personal fees from Novartis; serving on the steering committee of the Danish Rheumatology Quality Registry; and co-charing EuroSpA, which is partly funded by Novartis and UCB outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Inclusion
Only a subset of participants were invited to baseline visit as the majority was allocated to a control group in the REPLACE study, which became full. ACTH indicates adrenocorticotropic hormone (corticotropin).
Figure 2.
Figure 2.. Crude Prevalence Ratios (PRs) for Associations of Variables With Increased Likelihood of AddiQoL-30 Score 85 or Lower
Prednisolone cessation: time between last prednisolone dose and the corticotropin test. Charlson comorbidity index is scored without age. SI conversion factor: To convert cortisol to μg/dL divide by 27.588. GCA indicates giant cell arteritis; PMR, polymyalgia rheumatica; SPPB, Short Physical Performance Battery score.
Figure 3.
Figure 3.. Linear Regression Models of Basal Cortisol and Addison Disease-Specific Quality of Life Questionnaire (Addiqol-30) Score
A, Unadjusted linear regression. B, Multiple linear regression, adjusted for age, sex, body fat percentage, hand grip strength, and corticotropin stimulation test sample time. β-value is the slope, calculated as the AddiQol-30 score per 50 nmol/L cortisol. Removing the participant with basal cortisol higher than 600 nmol/L did not change the outcome. SI conversion factor: To convert cortisol to μg/dL divide by 27.588.
See this image and copyright information in PMC

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