SEARCHNARRATIVE_REVIEWendocrinology, internal medicine

narrative_review·endocrinology, internal medicine, rheumatology, pulmonology, gastroenterology·PMC10638606

Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad ?

Endocrine Reviews · 4 authors, 6 centres

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TL;DR

This narrative review synthesizes evidence on the prevalence, adverse effects, and emerging therapeutic strategies for mitigating side effects of exogenous glucocorticoid therapy across multiple organ systems.

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Limitations include the observational nature of most underlying data, confounding by inflammation severity, and the scarcity of comprehensive adverse event data from randomized controlled trials.

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narrative_review

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endocrinology

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100% · A

ORIGINAL PAPER

PMC10638606

Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad ?

Endocrine Reviews

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ABSTRACT

Abstract It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome , are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy. Keywords: steroid hormones, adverse effects, 11β-hydroxysteroid dehydrogenase type 1 inhibition, SEGRA, chronopharmacology

CITATION EXPORT

Riccardo Pofi, Giorgio Caratti, David W Ray et al.. Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?. Endocrine Reviews. (2023). https://doi.org/10.1210/endrev/bnad016

AUTHORS

4 · 6 CENTRES

Riccardo Pofi, Giorgio Caratti, David W Ray, Jeremy W Tomlinson

1 Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
2 Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
3 Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
4 NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK
5 Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford OX37LE, UK
6 Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK