The hypothalamic-pituitary-adrenal (HPA) axis
The normal production of cortisol is controlled by the HPA axis, a negative feedback loop that adapts to multiple factors2,5
Mechanism of Disease
EXCESS CORTISOL AND ITS EFFECTS ON THE BODY
Cortisol is the most abundant endogenous glucocorticoid in the human body. It plays an important function in regulating physiological processes, including1,2:
Metabolism
Immune Response
Cardiovascular Function
When left untreated over a long period of time, excess cortisol can negatively affect the body and cause multisystemic dysfunction, including increased risk for cardiovascular disease.3,4
*ACTH also stimulates the release of DHEA-S into the bloodstream. Low-serum DHEAS levels have been shown to be a marker of excess cortisol in patients with ACTH-independent hypercortisolism.6
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THE DISRUPTION OF THE HPA AXIS AND HYPERCORTISOLISM
Hypercortisolism occurs when the body is exposed to high levels of cortisol. There are 2 general causes of endogenous hypercortisolism.5
ACTH-dependent hypercortisolism5
Secretion of ACTH from a pituitary adenoma stimulates the adrenal glands to secrete excess cortisol (Cushing disease).
Secretion of ACTH from an ectopic tumor stimulates the adrenal glands to secrete excess cortisol.
ACTH-independent hypercortisolism5
Secretion of cortisol from an adrenal source causes autonomous cortisol secretion (Cushing syndrome).
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References
1. Jovanovic F, Jovanovic V, Knezevic NN. Cells. 2023;12(8):1178. doi:10.3390/cells12081178 2. Dickerson SS, Kemeny ME. Psychol Bull. 2004;130(3):355-391. doi:10.1037/0033-2909.130.3.355 3. Raff H, Sharma ST, Nieman LK. Compr Physiol. 2014;4(2):739-769. doi:10.1002/cphy.c130035 4. Di Dalmazi G, Vicennati V, Garelli S, et al. Lancet Diabetes Endocrinol. 2014;2(5):396-405. doi:10.1016/S2213-8587(13)70211-0 5. Guaraldi F, Salvatori R. J Am Board Fam Med. 2012;25(2):199-208. doi:10.3122/jabfm.2012.02.110227 6. Chiodini I, Ramos-Rivera A, Marcus AO, Yau H. J Endocr Soc. 2019;3(5):1097-1109. doi:10.1210/js.2018-00382 7. Chiodini I, Torlontano M, Scillitani A, et al. Eur J Endocrinol. 2005;153(6):837-844. doi:10.1530/eje.1.02045 8. Catargi B, Rigalleau V, Poussin A, et al. J Clin Endocrinol Metab. 2003;88(12):5808-5813. doi:10.1210/jc.2003-030254 9. Costa DS, Conceição FL, Leite NC, Ferreira MT, Salles GF, Cardoso CR. J Diabetes Complications. 2016;30(6):1032-1038. doi:10.1016/j.jdiacomp.2016.05.006