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, though 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
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, 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 the
axis suppression from physiological doses.