What is cortisol?
Cortisol is a steroid hormone that is synthesized in your body from cholesterol. Although cholesterol may be obtained from the diet, it is also manufactured by your liver. It then follows one of several steroidogenic pathways in the adrenal glands, where it is eventually converted to cortisol, which is the active form of the hormone.
The production and release of cortisol, depends on the hypothalamus-pituitary-adrenal axis (HPA axis). These three endocrine glands work together to regulate cortisol and maintain homeostasis within your body. When you experience a stressor, it activates the parvocellular nuclei (PVN) in your hypothalamus gland. This leads to a release of corticotrophin-releasing hormone (CRH).
CRH acts on the anterior pituitary gland to promote the production and secretion of adrenocorticotrophic hormone (ACTH). ACTH is released into your veins and reaches the adrenal cortex, where it binds to the melanocyte type-2 receptor (MC2R) on cells and stimulates cortisol release into the bloodstream. This process is regulated by negative feedback inhibition, which means that cortisol can inhibit ACTH and CRH secretion to maintain homeostasis. (5)(10) In other words, as more cortisol is secreted by the adrenal glands, the negative feedback loop ensures ACTH and CRH secretion is decreased.
How does cortisol affect health?
When released into the bloodstream, cortisol has several physiologic effects, including:
- Adjusting respiration and muscle tension
- Down-regulating digestive and reproductive functions
- Increasing blood glucose level
- Increasing heart rate
- Raising blood pressure
- Reducing inflammation (1)(4)
The purpose of these effects is to allow your brain and body to respond and protect you from a stressor.
Beyond the stress response, cortisol also plays a role in your wake-sleep cycle and in maintaining serum glucose (blood sugar) levels. Cortisol levels should naturally peak in the morning between 6 am and 9 am, and be at their lowest from 11 pm and 1 am. As you are fasting overnight, cortisol levels begin to rise around 4 am in order to maintain blood glucose levels. (10)
While cortisol is essential to maintaining daily functions, chronic stress and other lifestyle factors can result in cortisol dysfunction. Dysfunction may involve depletion of cortisol, low free (or unbound) cortisol, issues with cortisol secretion or CRH function, glucocorticoid receptor resistance, or hypersensitivity of the negative feedback system. (4)
Insufficient cortisol
Since cortisol is made in the adrenal glands, sufficient adrenal function is necessary to produce the hormone. Adrenal insufficiency can come in several forms, including Addison’s disease, secondary adrenal insufficiency, and tertiary adrenal insufficiency. (13)
Some of the factors that contribute to adrenal insufficiency include:
- Autoimmune disease or infections such as tuberculosis (Addison’s disease)
- Conditions that affect the pituitary gland, such as tumors, infections, or genetic diseases (secondary adrenal insufficiency)
- Long-term use of corticosteroids followed by abruptly stopping the medication (tertiary adrenal insufficiency) (13)
Addison’s disease, also known as adrenal insufficiency, is characterized by low cortisol levels. In Western countries, about 120 people per million suffer from this disease. The signs and symptoms include fatigue, weight loss, vomiting, diarrhea, abdominal pain, and behavioral changes. Corticosteroid and mineralocorticoid replacement therapies are used for the treatment of Addison’s disease. (14)
Another serious and potentially life-threatening condition related to insufficient cortisol is central adrenal insufficiency (CAI). CAI can be caused by either pituitary disease or impaired hypothalamic function, resulting in ACTH deficiency and other potential pituitary hormone deficiencies. When ACTH secretion decreases, cortisol secretion subsequently decreases as well resulting in several symptoms such as hypoglycemia, lethargy, apnea, jitteriness, and seizures. (9)
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Excess cortisol
Cortisol imbalance can also affect your health when your body produces too much cortisol. While normal increases in cortisol levels occur as a result of moderate to intense exercise (6), prolonged cortisol exposure may lead to certain health conditions.
Causes of high cortisol levels include:- Children’s exposure to maternal postnatal depression
- Chronic stress, including shift work and intensive training in endurance athletes (3)(5)(7)(12)
- A higher body mass index (BMI) or obesity
- An irregular inflammatory response when injured, resulting in impaired healing
- Inflammation, depression, and pain
- Negative effects on cognition; may contribute to Alzheimer’s disease pathology (4)(8)(11)
The bottom line
Navigating cortisol levels can be complicated but is critical for optimal health. If you’re a patient and experiencing chronic stress or suspect you may have a cortisol imbalance, work with an integrative healthcare practitioner to evaluate your current status and learn how to regulate your stress response.- Cortisol | Hormone Health Network. (n.d.). Retrieved May 13, 2019, from https://www.hormone.org/hormones-and-health/hormones/cortisol
- Cruess, D. G., Antoni, M. H., Mcgregor, B. A., Kilbourn, K. M., Boyers, A. E., Alferi, S. M., . . . Kumar, M. (2000). Cognitive-Behavioral Stress Management Reduces Serum Cortisol By Enhancing Benefit Finding Among Women Being Treated for Early Stage Breast Cancer. Psychosomatic Medicine, 62(3), 304-308. doi:10.1097/00006842-200005000-00002
- Halligan, S. L., Herbert, J., Goodyer, I. M., & Murray, L. (2004). Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biological Psychiatry, 55(4), 376-381. doi:10.1016/j.biopsych.2003.09.013
- Hannibal, K. E., & Bishop, M. D. (2014). Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneuroendocrine Rationale for Stress Management in Pain Rehabilitation. Physical Therapy, 94(12), 1816-1825. doi:10.2522/ptj.20130597
- Herman, J. P., McKlveen, J. M., Ghosal S., Kopp, B., Wulsin, A., Makinson, R. . . . Myers, B. (2016). Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. Comprehensive Physiology, 6(2), 603-21. doi:10.1002/cphy.c150015
- Hill, E. E., Zack, E., Battaglini, C., Viru, M., Viru, A., & Hackney, A. C. (2008). Exercise and circulating Cortisol levels: The intensity threshold effect. Journal of Endocrinological Investigation, 31(7), 587-591. doi:10.1007/bf03345606
- Manenschijn, L., Rulanda G. P. M. Van Kruysbergen, G. P., De Jong, F. H., Koper, J. W., & Van Rossum, E. F. (2011). Shift Work at Young Age Is Associated with Elevated Long-Term Cortisol Levels and Body Mass Index. The Journal of Clinical Endocrinology & Metabolism, 96(11), E1862-E1865. doi:10.1210/jc.2011-1551
- Ouanes, S., Popp, J. (2019). High Cortisol and the Risk of Dementia and Alzheimer’s Disease: A Review of the Literature. Frontiers in Aging Neuroscience, 11(43), doi:10.3389/fnagi.2019.00043.
- Patti, G., Guzzeti, C., Di Iorgi, N., Maria Allegri, A.E., Napoli, F., Loche, S., Maghnie, M. (2018). Central adrenal insufficiency in children and adolescents. Best Practice & Research Clinical Endocrinology & Metabolism, 32(4), 425-444. doi: 10.1016/j.beem.2018.03.012
- Raff, H., Sharma, S. T., & Nieman, L. K. (2014). Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushings Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia. Comprehensive Physiology, 4(2), 739-769. doi:10.1002/cphy.c130035
- Rask, E., Olsson, T., Soderberg, S., Andrew, R., Livingstone, D.E.W., Johnson, O., Walker, B.R. (2001). Tissue-Specific Dysregulation of Cortisol Metabolism in Human Obesity. The Journal of Clinical Endocrinology & Metabolism, 86(3), 1418–1421. doi:10.1210/jcem.86.3.7453
- Skoluda, N., Dettenborn, L., Stalder, T., & Kirschbaum, C. (2012). Elevated hair cortisol concentrations in endurance athletes. Psychoneuroendocrinology, 37(5), 611-617. doi:10.1016/j.psyneuen.2011.09.001
- Symptoms and Causes for Adrenal Insufficiency & Addison’s Disease. (2018, September 01). Retrieved May 13, 2019, from https://www.niddk.nih.gov/health-information/endocrine-diseases/adrenal-insufficiency-addisons-disease
- Ten, S., New, M., Maclaren, N. (2001). Addison’s Disease 2001. The Journal of Clinical Endocrinology & Metabolism, 86(7), 2909–2922. doi: 10.1210/jcem.86.7.7636
