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Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System
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Int. J. Mol. Sci. 2017, 18(10), 2201; doi:10.3390/ijms18102201

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

Unit of Endocrinology, Università Cattolica del Sacro Cuore, Largo “A. Gemelli” 8, I-00168 Rome, Italy
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Received: 11 September 2017 / Revised: 16 October 2017 / Accepted: 18 October 2017 / Published: 20 October 2017
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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. View Full-Text
Keywords: synthetic glucocorticoid; tertiary hypoadrenalism; iatrogenic Cushing’s syndrome synthetic glucocorticoid; tertiary hypoadrenalism; iatrogenic Cushing’s syndrome
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Paragliola, R.M.; Papi, G.; Pontecorvi, A.; Corsello, S.M. Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis. Int. J. Mol. Sci. 2017, 18, 2201.

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