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 DHEAS into the bloodstream. Low-serum DHEAS levels have been shown to be a marker of excess cortisol in people 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 adenoma causes excess autonomous cortisol secretion (Cushing syndrome).
Want to see the differences between ACTH-dependent and ACTH-independent hypercortisolism?
Nearly 1 in 4 people with difficult-to-control T2D had endogenous hypercortisolism7
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. Buse JB, Kahn SE, Aroda VR, et al. Prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes: updated results from CATALYST part 1 [symposium]. Presented by Fonseca, V. at the 22nd World Congress Insulin Resistance Diabetes & Cardiovascular Disease; December 12-14, 2024; Los Angeles, CA. 8. DeFronzo RA, Auchus RJ, Bancos I, et al. BMJ Open. 2024;14(7):e081121. doi:10.1136/bmjopen-2023-081121