ArticleEndocrine connections2026
Glucocorticoid-induced adrenal insufficiency: physiological dose tapering promotes recovery.
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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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.
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