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Review
. 2017 Oct 20;18(10):2201.
doi: 10.3390/ijms18102201.

Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis

Rosa Maria Paragliola  1 , Giampaolo Papi  2 , Alfredo Pontecorvi  3 , Salvatore Maria Corsello  4
Affiliations
Review

Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis

Rosa Maria Paragliola et al. Int J Mol Sci. .

Abstract

Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for several diseases in consideration of both anti-inflammatory and immunosuppressive activity but, if used at high doses for prolonged periods, it can determine the systemic effects characteristic of Cushing's syndrome. In addition to signs and symptoms of hypercortisolism, patients on chronic GC therapy are at risk to develop tertiary adrenal insufficiency after the reduction or the withdrawal of corticosteroids or during acute stress. This effect is mediated by the negative feedback loop on the hypothalamus-pituitary-adrenal (HPA) axis, which mainly involves corticotropin-release hormone (CRH), which represents the most important driver of adrenocorticotropic hormone (ACTH) release. In fact, after withdrawal of chronic GC treatment, reactivation of CRH secretion is a necessary prerequisite for the recovery of the HPA axis. In addition to the well-known factors which regulate the degree of inhibition of the HPA during synthetic GC therapy (type of compound, method of administration, cumulative dose, duration of the treatment, concomitant drugs which can increase the bioavailability of GCs), there is a considerable variation in individual physiology, probably related to different genetic profiles which regulate GC receptor activity. This may represent an interesting basis for possible future research fields.

Keywords: iatrogenic Cushing’s syndrome; synthetic glucocorticoid; tertiary hypoadrenalism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Daily cortisol rhythm in healthy volunteers [23].
Figure 2
Figure 2
Corticotropin-release hormone (CRH) knock-out (KO) mouse model in regulation of hypothalamus-pituitary-adrenal (HPA) axis [59]. In CRH KO models proopiomelanocortin (POMC) mRNA, but not plasmatic adrenocorticotropic hormone (ACTH), rises after adrenalectomy. Glucocorticoids, but not mineralocorticoids (blue dotted arrow) reduce POMC increase induced by adrenalectomy. CRH administration restores a significant ACTH secretion.
Figure 3
Figure 3
Tissue side effects of synthetic glucocorticoids [1].
See this image and copyright information in PMC

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