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Review
. 2025 Jan;48(1):37-52.
doi: 10.1007/s40618-024-02461-9. Epub 2024 Oct 1.

Glucocorticoid treatment and adrenal suppression in children: current view and open issues

Nicola Improda  1 , Laura Chioma  2 , Donatella Capalbo  3 , Carla Bizzarri  2 , Mariacarolina Salerno  4
Affiliations
Review

Glucocorticoid treatment and adrenal suppression in children: current view and open issues

Nicola Improda et al. J Endocrinol Invest. 2025 Jan.

Abstract

Purpose: Glucocorticoids (GCs) are commonly used for several acute and chronic pediatric diseases. However, chronic treatment may result in hypothalamic-pituitary-adrenal axis (HPA) dysfunction. Glucocorticoid-induced adrenal insufficiency (GI-AI) is indeed the most frequent cause of adrenal insufficiency (AI) in children, possibly resulting in a life-threatening event such as adrenal crisis (AC). It is generally underestimated, especially when using non-systemic glucocorticoid formulations. This review aims at summarizing current evidence on the effects of long-term GC treatment on the HPA axis, management of GC tapering and assessment of the HPA recovery.

Methods: We conducted a narrative review of the relevant literature focusing on pathogenic mechanisms, predictive factors, diagnosis and treatment of GI-AI.

Results: All types of GCs, whatever the route of administration, may have suppressive effects on the HPA axis, especially when compounds with higher potency and long half-life are used. Moreover, chronic GC administration is the most common cause of Cushing syndrome in children. In order to overcome the risk of GI-AI, slow withdrawal of GCs is necessary. When approaching the replacement dose, it is recommended to switch to shorter half-life formulations such as hydrocortisone. Assessment of HPA axis recovery with basal and stimulated cortisol levels may help detecting children at risk of AC that may require hydrocortisone supplementation.

Conclusion: The management of GI-AI in children is challenging and many areas of uncertainty remain. Improving the knowledge on long-term GC effects on HPA in children, the management of steroid discontinuation and emergency dosing may help preventing GI-AI symptoms and acute hospital admission for AC.

Keywords: Adrenal crisis; Adrenal suppression; Glucocorticoid replacement; Glucocorticoid-induced adrenal insufficiency; Steroid treatment.

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Conflict of interest statement

Declarations. Competing interests: The authors hereby declare that there are no financial or non-financial interests that are directly or indirectly related to this work.

Figures

Fig. 1
Fig. 1
Pathophysiology of glucocorticoid-induced adrenal insufficiency
Fig. 2
Fig. 2
Management of glucocorticoid withdrawal and assessment of adrenal axis recovery
See this image and copyright information in PMC

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