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Cited by 30Adrenal Hormones and DisordersHormonal Regulation and HypertensionStress Responses and Cortisol

Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy

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Dineen, Rosemary, Stewart, Paul M., Sherlock, Mark·2019·Clinical Endocrinology
DOI 10.1111/cen.13837
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Abstract

Summary: Glucocorticoids (GC s) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic‐pituitary‐adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life‐threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue‐specific regulation of glucocorticoid through the two isozymes of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy.

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  • The addition of concomitant medication that alters cortisol metabolism could potentially precipitate an adrenal crisis.

    “The addition of concomitant medication that alters cortisol metabolism could potentially precipitate an adrenal crisis.40”

    From Adrenal crisis: prevention and management in adult patients (2019) · cites this paper as [40]

  • Medications that induce the drug-metabolizing enzyme CYP3A4 including carbamazepine, Hypericum perforatum, mitotane and rifampicin increase cortisol clearance, necessitating a higher replacement dose.

    “Medications that induce the drug-metabolizing enzyme CYP3A4 including carbamazepine, Hypericum perforatum (St. John’s wort), mitotane and rifampicin also increase cortisol clearance, necessitating a higher replacement dose.40”

    From Adrenal crisis: prevention and management in adult patients (2019) · cites this paper as [40]

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Cited by

Sorted by citations

Authors
Dineen, R., Stewart, P. M., & Sherlock, M.
Affiliations
  • Royal College of Surgeons in Ireland (IE)
  • University of Leeds (GB)
Corresponding author
Sherlock, Mark
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2018-09-24
Volume
90
Issue
1
Pages
3-14
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/cen.13837
OpenAlex
W2887776682
Cited by
30
References
23
Citations by year
2026: 1 · 2025: 7 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 2
FWCI
0.38
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
Funders
  • Meath Foundation
  • Irish Research Council
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
glucocorticoids, adrenal insufficiency, glucocorticoid replacement therapy, cortisol, cortisol deficiency, 11β-hydroxysteroid dehydrogenase, hypothalamic-pituitary-adrenal axis, ACTH, glucocorticoid adverse effects
MeSH terms
Addison Disease, Adrenal Insufficiency, Glucocorticoids, Humans, Hydrocortisone, Hormone Replacement Therapy

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