Adrenocorticotropic Hormone (ACTH) Resistance

// Christopher T. Arick, DC, MS

Adrenocorticotropic Hormone (ACTH) Resistance

Clinicians may have heard the term ACTH resistance being tossed around clinical seminars and conferences related to adrenal function. These may all be descriptors or variants of ACTH resistance as an aspect of clinical presentation. It is first important to point out that ACTH resistance is also a rare hereditary defect that is usually first detected at birth with symptoms of darkened pigment and feeding problems. These babies are found to have high ACTH levels and low cortisol levels in the blood.1 Perhaps a unique term should be coined to refer to ACTH resistance that is related to lifestyle health, stress, and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis.
Perhaps a unique term should be coined to refer to ACTH resistance that is related to lifestyle health, stress, and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis.In normal physiology, corticotropin releasing hormone (CRH) is secreted by the hypothalamus to stimulate the anterior pituitary which then secretes adrenocorticotropic hormone (ACTH) to stimulate the adrenal glands to secrete a number of substances including cortisol. There is regulation of the production of both CRH and ACTH if stimulation appears to be more than is needed or can be handled by the body.2  During times of long-term, repeated stressors, the hypothalamus and pituitary can be targets of stimulation from the neuroimmunoendocrine system to increase the production of hormones of the adrenal glands to point that their production has been depleted or their recognition of ACTH has been decreased.3,4
This is analogous to what happens to insulin. Insulin docks at GLUT4 receptor sites and allows glucose to enter the cell under normal circumstances. Long-term, repeated reliance on endogenous insulin can create a scenario where more of the body’s own insulin is required to stimulate GLUT4 and the cell can become resistant to the effects of insulin over time. This is a spectrum of function.
Patients that suffer from challenges of lifestyle health present frequently requiring HPA axis support. This may include ACTH resistance which stems mostly from the cell-to-cell mediator burden of our patients. Cytokines can affect the HPA axis as part of physical, mental, or chemical stressors which may include microbial balance, health status, and perhaps even long-forgotten injury.5 Some of the most challenging cases in an ambulatory clinic, who have been to numerous practitioners without adequate answers, may have adrenal glands that are less responsive to ACTH than normal controls.3 There have been connections to the regulation of immunity to HPA axis function.6

Christopher T. Arick, DC, MS

Christopher T. Arick, DC, MS is an assistant professor at National University of Health Sciences-Florida, where he teaches clinical laboratory diagnosis, gastrointestinal/genitourinary evaluation and management, and dermatology. He is director of BioPhysia, a clinical education organization specializing in functional medicine, nutrition, and genomic testing. Dr. Arick is also a PhD candidate at the University of South Florida in Higher Education researching integrative medicine.

1. Huebner, A., L. L. Elias, and A. J. Clark. "ACTH resistance ..." Journal of pediatric endocrinology & metabolism: JPEM 12 (1999): 277-293.
2. Buckley, Theresa M., and Alan F. Schatzberg. "On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders." The Journal of Clinical Endocrinology & Metabolism 90.5 (2005): 3106-3114.
3. Demitrack, Mark A., and Leslie J. Crofford. "Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation ..." Annals of the New York Academy of Sciences 840.1 (1998): 684-697.
4. Silverman, Marni N., and Esther M. Sternberg. "Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction." Annals of the New York Academy of Sciences 1261.1 (2012): 55-63.
5. Turnbull, Andrew V., and Catherine L. Rivier. "Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. "Physiological reviews 79.1 (1999): 1-71.
6. Del Rey, A., and H. O. Besedovsky. "The cytokine-HPA axis circuit contributes to prevent or moderate ..." Zeitschrift für Rheumatologie 59.2 (2000): II31-II35.

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