Physiological dose tapering promotes hypothalamic-pituitary-adrenal axis recovery in glucocorticoid-induced adrenal insufficiency

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

doi:10.1530/endoabs.117.P1

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Endocrine Abstracts (2026) 117 P1 | DOI: 10.1530/endoabs.117.P1

SFEBES2026 Poster Presentations Adrenal and Cardiovascular (54 abstracts)

Physiological dose tapering promotes hypothalamic-pituitary-adrenal axis recovery in glucocorticoid-induced adrenal insufficiency

Rajeev Mehta ¹ , Katharine Lazarus ^1,2 , Angelica Sharma ^1,2 , Pei Chia Eng ^1,3 , Kavita Narula ^1,2 , Sirazum Choudhury ^1,2,4 , Deborah Papadopoulou ² , Zin Htut ^1,2 , Tricia Tan ^1,2,4 & Karim Meeran ^1,2

Author affiliations

¹Section of Endocrinology and Investigative Medicine, Imperial College London, London, United Kingdom; ²Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom; ³Department of Endocrinology, National University Hospital, Singapore, Singapore; ⁴Department of Clinical Biochemistry, Northwest London Pathology, London, United Kingdom

Background: Glucocorticoid (GC) discontinuation is hindered by risk of GC-induced adrenal insufficiency (GC-AI). 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 low likelihood of hypothalamic-pituitary-adrenal (HPA) axis recovery, though this assumes no axis suppression from such doses. We aim to evaluate how HPA axis function evolves during physiological dose tapering and assess whether current cortisol thresholds restrict successful discontinuation.

Methods: This retrospective cohort study evaluated 65 adults with long-term GC use for inflammatory disease undergoing prednisolone tapering at our tertiary endocrine centre between 2019 and 2024. Linear mixed-effects modelling was used to assess serial short Synacthen tests (n = 52) on reducing prednisolone doses (≤5 mg).

Results: Mean age at referral 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 taper attempts (n = 47), 81% (n = 38) successfully weaned. Sixteen patients with a nadir morning cortisol <150 nmol/l while on a prednisolone dose ≤5 mg, including six with undetectable (<28 nmol/l) values, safely and successfully discontinued prednisolone. No adrenal crises occurred. All three patients who failed to wean due to insufficient HPA axis recovery had adequate 8-hour prednisolone replacement levels on 2 mg, suggesting this dose constituted full physiological replacement.

Conclusion: HPA axis function in GC-AI improves with dose reduction, even at physiological doses, and structured, symptom-led tapering is safe and effective. Pharmacokinetic variability may explain why some experience persistent axis suppression. Future guidelines should consider the suppressive effects of physiological doses, with HPA axis recovery following, rather than preceding, successful weaning.