Sarkar S, Abeyagunawardena AS, Sinha R. Impact of glucocorticoid therapy on hypothalamic-pituitary-adrenal axis function in pediatric nephrotic syndrome: A narrative review. World J Clin Pediatr 2025; 14(4): 110374 [DOI: 10.5409/wjcp.v14.i4.110374]
Corresponding Author of This Article
Rajiv Sinha, Division of Paediatric Nephrology, Institute of Child Health, Kolkata, Biresh Guha Street, Kolkata 700017, India. rajivsinha_in@yahoo.com
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Pediatrics
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 9, 2025 (publication date) through Oct 31, 2025
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Publication Name
World Journal of Clinical Pediatrics
ISSN
2219-2808
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Sarkar S, Abeyagunawardena AS, Sinha R. Impact of glucocorticoid therapy on hypothalamic-pituitary-adrenal axis function in pediatric nephrotic syndrome: A narrative review. World J Clin Pediatr 2025; 14(4): 110374 [DOI: 10.5409/wjcp.v14.i4.110374]
Subhankar Sarkar, Department of Pediatrics, All India Institute of Medical Sciences, Kalyani, Kolkata 700019, West Bengal, India
Asiri Samantha Abeyagunawardena, Department of Pediatrics, University of Peradeniya, Peradeniya, 20400, Sri Lanka
Rajiv Sinha, Division of Paediatric Nephrology, Institute of Child Health, Kolkata, Kolkata 700017, India
Author contributions: Sarkar S performed the literature review, analyzed the data, and prepared the initial draft of the manuscript; Abeyagunawardena AS contributed to the interpretation of findings and provided critical revisions; Sinha R conceptualized the review, provided supervision, and finalized the manuscript; all authors reviewed and approved the final version.
Conflict-of-interest statement: We declare that there is no conflict of interest regarding the publication of this manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Rajiv Sinha, Division of Paediatric Nephrology, Institute of Child Health, Kolkata, Biresh Guha Street, Kolkata 700017, India. rajivsinha_in@yahoo.com
Received: June 6, 2025 Revised: June 29, 2025 Accepted: September 18, 2025 Published online: December 9, 2025 Processing time: 147 Days and 14.4 Hours
Abstract
Glucocorticoids (GCs) such as prednisolone are widely used in conditions like nephrotic syndrome, asthma, and autoimmune diseases. However, prolonged or high-dose use may suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to secondary adrenal insufficiency (AI). This condition occurs when the adrenal glands fail to produce adequate cortisol, which is essential for regulating metabolism, immune response, and stress adaptation. Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates the pituitary to release adrenocorticotropic hormone (ACTH), which then triggers cortisol production in the adrenal glands. Prolonged GC use disrupts this system by inhibiting CRH and ACTH secretion, leading to adrenal atrophy and reduced cortisol production. HPA axis suppression is primarily diagnosed through dynamic tests. Early morning cortisol levels above > 18 ng/mL typically indicate normal function, while levels < 3 ng/mL suggest AI. Intermediate values require additional testing, such as the insulin tolerance test, ACTH stimulation test, and metyrapone test. Prednisolone in nephrotic syndrome suppresses the HPA axis, heightening AI risk, influenced by dose, duration, and timing of administration. Careful GC management is essential to balance disease control with risks of HPA axis suppression. Early recognition and timely intervention can prevent adrenal crises and improve outcomes in pediatric patients.
Core Tip: Children with nephrotic syndrome often require repeated glucocorticoid therapy, which can lead to hypothalamic-pituitary-adrenal axis suppression and secondary adrenal insufficiency. This impaired stress response may contribute to relapse during infections. This review summarizes the mechanisms, diagnostic methods, clinical implications, and preventive strategies, underscoring the need for early identification and tailored steroid management to reduce long-term risks.
