Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

Simon Bøggild Hansen; Anja Fenger Dreyer; Nanna Thurmann Jørgensen; Hajir Al-Jorani; Lise Sofie Bislev; Victor Brun Boesen; Stina Willemoes Borresen; Louise Lehmann Christensen; Dorte Glintborg; Ellen Margrethe Hauge; Merete Lund Hetland; Richard Christian Jensen; Søren Andreas Just; Kresten Krarup Keller; Marianne Klose; Kristina Laugesen; Henning Locht; Marie Louise Lund; Jelena Stankovic; Paul M. Stewart; Randi Maria Hanghøj Tei; Anne Voss; Ulla Feldt-Rasmussen; Jens Otto L. Jørgensen; Marianne Skovsager Andersen

doi:10.1001/jamanetworkopen.2025.1029

Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

Simon Bøggild Hansen, Anja Fenger Dreyer, Nanna Thurmann Jørgensen, Hajir Al-Jorani, Lise Sofie Bislev, Victor Brun Boesen, Stina Willemoes Borresen, Louise Lehmann Christensen, Dorte Glintborg, Ellen Margrethe Hauge, Merete Lund Hetland, Richard Christian Jensen, Søren Andreas Just, Kresten Krarup Keller, Marianne Klose, Kristina Laugesen, Henning Locht, Marie Louise Lund, Jelena Stankovic, Paul M. StewartRandi Maria Hanghøj Tei, Anne Voss, Ulla Feldt-Rasmussen, Jens Otto L. Jørgensen, Marianne Skovsager Andersen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Journal	JAMA network open
Volume	8
Issue	3
Pages (from-to)	e251029
ISSN	2574-3805
DOIs	https://doi.org/10.1001/jamanetworkopen.2025.1029
Publication status	Published - Mar 2025

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10.1001/jamanetworkopen.2025.1029

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Hansen, S. B., Dreyer, A. F., Jørgensen, N. T., Al-Jorani, H., Bislev, L. S., Boesen, V. B., Borresen, S. W., Christensen, L. L., Glintborg, D., Hauge, E. M., Hetland, M. L., Jensen, R. C., Just, S. A., Keller, K. K., Klose, M., Laugesen, K., Locht, H., Lund, M. L., Stankovic, J., ... Andersen, M. S. (2025). Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone. JAMA network open, 8(3), e251029. https://doi.org/10.1001/jamanetworkopen.2025.1029

@article{d8b3a6ea095545feaf8378f0e387b1d6,

title = "Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone",

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.",

author = "Hansen, {Simon B{\o}ggild} and Dreyer, {Anja Fenger} and J{\o}rgensen, {Nanna Thurmann} and Hajir Al-Jorani and Bislev, {Lise Sofie} and Boesen, {Victor Brun} and Borresen, {Stina Willemoes} and Christensen, {Louise Lehmann} and Dorte Glintborg and Hauge, {Ellen Margrethe} and Hetland, {Merete Lund} and Jensen, {Richard Christian} and Just, {S{\o}ren Andreas} and Keller, {Kresten Krarup} and Marianne Klose and Kristina Laugesen and Henning Locht and Lund, {Marie Louise} and Jelena Stankovic and Stewart, {Paul M.} and Tei, {Randi Maria Hangh{\o}j} and Anne Voss and Ulla Feldt-Rasmussen and J{\o}rgensen, {Jens Otto L.} and Andersen, {Marianne Skovsager}",

year = "2025",

month = mar,

doi = "10.1001/jamanetworkopen.2025.1029",

language = "English",

volume = "8",

pages = "e251029",

journal = "JAMA network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "3",

}

Hansen, SB, Dreyer, AF, Jørgensen, NT, Al-Jorani, H, Bislev, LS, Boesen, VB, Borresen, SW, Christensen, LL, Glintborg, D, Hauge, EM, Hetland, ML, Jensen, RC, Just, SA, Keller, KK, Klose, M, Laugesen, K, Locht, H, Lund, ML, Stankovic, J, Stewart, PM, Tei, RMH, Voss, A, Feldt-Rasmussen, U, Jørgensen, JOL & Andersen, MS 2025, 'Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone', JAMA network open, vol. 8, no. 3, pp. e251029. https://doi.org/10.1001/jamanetworkopen.2025.1029

Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone. / Hansen, Simon Bøggild; Dreyer, Anja Fenger; Jørgensen, Nanna Thurmann et al.
In: JAMA network open, Vol. 8, No. 3, 03.2025, p. e251029.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

AU - Hansen, Simon Bøggild

AU - Dreyer, Anja Fenger

AU - Jørgensen, Nanna Thurmann

AU - Al-Jorani, Hajir

AU - Bislev, Lise Sofie

AU - Boesen, Victor Brun

AU - Borresen, Stina Willemoes

AU - Christensen, Louise Lehmann

AU - Glintborg, Dorte

AU - Hauge, Ellen Margrethe

AU - Hetland, Merete Lund

AU - Jensen, Richard Christian

AU - Just, Søren Andreas

AU - Keller, Kresten Krarup

AU - Klose, Marianne

AU - Laugesen, Kristina

AU - Locht, Henning

AU - Lund, Marie Louise

AU - Stankovic, Jelena

AU - Stewart, Paul M.

AU - Tei, Randi Maria Hanghøj

AU - Voss, Anne

AU - Feldt-Rasmussen, Ulla

AU - Jørgensen, Jens Otto L.

AU - Andersen, Marianne Skovsager

PY - 2025/3

Y1 - 2025/3

N2 - 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.

AB - 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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U2 - 10.1001/jamanetworkopen.2025.1029

DO - 10.1001/jamanetworkopen.2025.1029

M3 - Journal article

C2 - 40100216

AN - SCOPUS:105001451061

SN - 2574-3805

VL - 8

SP - e251029

JO - JAMA network open

JF - JAMA network open

IS - 3

ER -

Changes in Adrenal Function and Insufficiency Symptoms After Cessation of Prednisolone

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