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

Abstract

Glucocorticoids (GCs) 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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“…It has been used to treat certain types of breast (e.g., hormone receptor-positive, HER2-negative breast cancer) or prostate cancers [1][2][3][4][5]. Additionally, this compound has been studied as a treatment for other drug-resistant cancers or neuroendocrine tumors that include pituitary tumors [3,[6][7][8][9][10].…”

Computation of Robust Minimal Intervention Sets in Multi-Valued Biological Regulatory Networks

“…Predictions suggest that cortisol supplementation, applied alone or in combination with the modulation of other targets, offers maximal robustness. However, direct modulation of glucocorticoid levels with for example prednisone present with increased risks of adverse events associated with broad immunosuppression and metabolic upset (Dineen et al, 2018; Graziadio et al, 2018). Recent pharmacological advances are making this approach more feasible but these remain at the stage of phase I clinical trials (Hoffman et al, 2018).…”

Diverse etiologies, diagnostic approach, and management of primary adrenal insufficiency in pediatric age

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