Evidence mapPaperPMID 41489002Full record

ArticleEndocrine connections2026

Glucocorticoid-induced adrenal insufficiency: physiological dose tapering promotes recovery.

Rajeev Mehta, Katharine Lazarus, Angelica Sharma, Pei Chia Eng, Kavita Narula, Sirazum Choudhury, Deborah Papadopoulou, Zin Htut, Tricia M-M Tan, Karim Meeran

Abstract read
In one paragraph

Article in Endocrine connections, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Rajeev MehtaDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0009-0002-9001-4168
Katharine LazarusDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0003-0758-7839
Angelica SharmaDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0001-8180-6388
Pei Chia EngDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-4172-1344
Kavita NarulaDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-7453-9039
Sirazum ChoudhuryDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0003-2429-005X
Deborah PapadopoulouDepartment of Endocrinology, Imperial College Healthcare NHS Trust, London, UK.ORCID https://orcid.org/0000-0002-7557-7803
Zin HtutDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-0490-7836
Tricia M-M TanDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0001-5873-3432
Karim MeeranDivision of Endocrinology and Investigative Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-7112-2756

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Glucocorticoid discontinuation is complicated by glucocorticoid-induced adrenal insufficiency. Guidelines discourage tapering below physiological doses (prednisolone 3-6 mg) when morning cortisol is ≤300 nmol/L, with values <150 nmol/L thought to indicate persistent adrenal insufficiency, although this may underestimate hypothalamic-pituitary-adrenal axis suppression from such doses. We aim to evaluate how hypothalamic-pituitary-adrenal axis function evolves during physiological dose tapering and assess whether current cortisol thresholds restrict successful discontinuation. Design: This is a retrospective cohort study. Methods: Adults (n = 65) with long-term glucocorticoid use for inflammatory disease undergoing prednisolone tapering between 2019 and 2024 were included. Serial short Synacthen tests (n = 52) on reducing prednisolone doses (≤5 mg) were analysed using linear mixed-effects modelling. Nadir morning cortisol values at doses ≤5 mg from successful weans were compared with guideline thresholds. Results: At referral, the mean age was 55.4 ± 16.4 years, with median prednisolone dose and duration of therapy being 5 (3.5-5) mg and 23 (6.5-66.5) months, respectively. For each 1 mg dose reduction, morning and post-Synacthen cortisol rose by 48.8 nmol/L and 57.5 nmol/L (both P < 0.001), respectively, with reductions >2 mg producing larger cortisol increases than 1 mg reductions (both P < 0.05). Among completed wean attempts (n = 47), 81% (n = 38) were successful. Of these, 42% (n = 16) had a nadir morning cortisol <150 nmol/L, including six with values <28 nmol/L. No adrenal crises occurred. Conclusions: Physiological dose tapering in glucocorticoid-induced adrenal insufficiency enables, rather than follows, hypothalamic-pituitary-adrenal axis recovery, with structured, symptom-led tapering being safe and effective. Future guidelines should recognise that the HPA axis is suppressed by physiological doses. Significance statement: In this retrospective cohort study evaluating 65 adults with long-term glucocorticoid use for inflammatory disease undergoing prednisolone tapering, each 1 mg dose reduction from a maximum starting dose of 5 mg increased morning and post-Synacthen cortisol by 48.8 nmol/L and 57.5 nmol/L (both P < 0.001), respectively, with reductions >2 mg producing larger cortisol increases than 1 mg reductions (both P < 0.05). Furthermore, sixteen patients with a nadir morning cortisol <150 nmol/L, including six with values <28 nmol/L, were able to safely and successfully discontinue prednisolone. These findings have important implications for the management of glucocorticoid-induced adrenal insufficiency, with hypothalamic-pituitary-adrenal axis recovery driven by physiological dose reduction itself, and successful tapering enabling rather than following axis recovery. The routine use of short Synacthen tests in glucocorticoid-induced adrenal insufficiency is not supported by this study.

Indexed as

cortisolglucocorticoid-induced adrenal insufficiencyhypothalamic–pituitary–adrenal axisprednisoloneprednisonetapering

Identifiers

PMID41489002
PMCPMC12811712

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.