How Cortisol Inhibits Active Thyroid Hormone and Suppresses Your Immune System

Studies show that cortisol, your body’s stress hormone, increases thyroid-stimulating hormone (TSH), (1,2) as well as inhibits the conversion of T4 to T3, which is your body’s metabolically active thyroid hormone (3,4). This process mostly occurs peripherally in the liver, GI tract, skeletal muscle, but also occurs in the thyroid and even the brain itself. However, we need more studies verifying exactly how elevated cortisol levels mechanistically inhibits T4-to-T3 conversion.

Thyroid hormone acts to regulate metabolism by increasing basal metabolic rate, temperature, and heart rate/cardiac output. This, in part, explains why chronic stress can easily lead to hypothyroidism, because cortisol is literally turning off your metabolism. (5)

But why would cortisol inhibit T3 from being formed? Because T3 requires a lot of energy or ATP, to get stuff done in the body, and when the body is stressed, it needs to conserve energy so that it can act out of fight or flight.

Cortisol Is Increased by Stress and Hypoglycemia

There are two main stimuli (6) that lead to the release of cortisol from the zona fasciculata of your adrenal glands:

1. Stress
2. Hypoglycemia

What this basically means is that when your blood sugars are low, a stress response is mimicked in your body.

Relaxation (A Destressed State) and Hyperglycemia Inhibit Cortisol

So what inhibits cortisol? You guessed it:

1. Not being stressed
2. Hyperglycemia (having blood sugar that is too high)

Stress Can Be Physical or Psychological

Stress is a complex phenomenon which can be physical or psychological. Some examples of stressful events which are physical in nature include trauma, infection, or exercise. We already mentioned hypoglycemia. Psychological examples of stress include fear, bereavement, or anger.

Cortisol is Permissive

Did you know that cortisol is the only hormone in the body that has receptors on almost every cell. It must be pretty important then. And that’s why it goes everywhere, having no particular affinity for anything. There’s a word for this in science: Permissive. (7) When you’re superstressed, all of these cortisol receptors get upregulated, increasing cellular sensitivity. And there is no cellular second messenger, in case you were wondering. The message of cortisol is loud and direct.

The Role of Cortisol

But what does cortisol do in the body? Well, two things, mainly, physiologically:

1. Proteolysis and Gluconeogenesis: Cortisol breaks down proteins, a process called proteolysis, so that the amino acids can be used to make glucose (gluconeogenesis). Remember, the body is in a state of hypoglycemia.
2. Stress Lowers Your Immune System: Cortisol wields profound anti-inflammatory effect across the body. Cortisol destroys white blood cells, such as T-cells and eosinophils. Cortisol inhibits the migration of pathogen-engulfing, debris-cleaning macrophages. Cortisol stabilizes mast cells, who can be quite annoying when they unload histamine, as in Type 1 hypersensitivity reactions, such as seasonal allergies.

Cortisol also inhibits an enzyme called phospholipase, which is responsible for making prostaglandins by cleaving the phospholipid bilayer in the cell’s membranes and releasing arachidonic acid, which signals the body to make a host of important inflammatory molecules required by the immune system to do its job. (8) Remind you of the effects of steroids, by chance? Well, that’s because cortisol is an endogenous steroid.

Immunosuppression

Too much cortisol can lead to immunosuppression. (9) And when your immune system is down, that’s when you get sick. Ever get done with school finals for the term, only to be sick during your week off? Well, this is why.

When you experience a stressful event, such as an important exam, a romantic breakup, or a fender-bender, a cascade of hormones (10) are released in the engine of your body over approximately twenty-four hours.

The Cascade of Stress Hormones

1. Epinephrine: First and immediately after the stressful event, epinephrine, aka adrenaline, is released. Epinephrine increases heart rate, raises blood sugar, and boost sugar metabolism.
2. Glucagon: After about 20 minutes, glucagon is released from the alpha cells of the pancreas, causing blood sugar to be raised, as well as glycogen to be broken down (glycogenolysis), fats to be broken down (lipolysis), and ketones to be made (ketogenesis). Glucagon acts on the adrenal cortex, as well as the liver and adipose tissue.
3. Cortisol: Within about 2 to 4 hours, cortisol is released.
4. Growth Hormone: Then, after about 24 hours, growth hormone (GH) is released. This is one reason that high intensity interval trainings (HIIT), such as CrossFit, is effective for muscle growth, which doesn’t occur until one gets good sleep and after a couple days, because workouts are fast-paced and stressful. GH raises glucose levels and breaks down fat, releasing free fatty acids, produced by the anterior pituitary when we sleep. This is why a good night’s sleep is critical to get the benefits of HIIT.
5. Insulin: Here’s one thing that’s a bit counterintuitive. Almost every metabolic process in the body is biphasic, balanced and counterbalanced by opposing regulatory feedback mechanisms. The hormones mentioned above will produce glucose in the body, which will increase the osmolarity of the blood. But after about 30 minutes, the body will release insulin, in order to push the excess glucose into the cells so that it can be used.
6. Antidiuretic Hormone (ADH): After about 30 minutes, the body will also produce antidiuretic hormone (ADH), in order to normalize the blood osmolarity by retaining fluid volume rather than diuresing (a fancy word for urinating).
7. Aldosterone: Cortisol works alongside the hormone aldosterone, as well, to increase sodium reabsorption in the kidneys, so that electrolyte and hydration status are appropriately maintained. As at least half of our blood is water, proper blood perfusion can occur in the body during fight or flight.

Conclusion

Cortisol, your body’s stress hormone, inhibits the conversion of T4 to T3, that is, your body’s metabolically active thyroid hormone.

If high cortisol levels are chronic, this can lead to hypothyroidism. Cortisol is the body’s endogenous corticosteroid, suppressing the immune system. Chronic stress can lead to frequently getting sick.

Resources:

1. Walter KN, Corwin EJ, Ulbrecht J, et al. Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women. Thyroid Research. 2012;5(1):13. doi:10.1186/1756-6614-5-13.
2. Hage MP, Azar ST. The Link between Thyroid Function and Depression. Journal of Thyroid Research. 2012;2012:1-8. doi:10.1155/2012/590648.
3. Szivak TK, Lee EC, Saenz C, et al. Adrenal Stress and Physical Performance During Military Survival Training. Aerospace Medicine and Human Performance. 2018;89(2):99-107. doi:10.3357/amhp.4831.2018.
4. Kahana L, Keidar S, Sheinfeld M, Palant A. Endogenous Cortisol And Thyroid Hormone Levels In Patients With Acute Myocardial Infarction. Clinical Endocrinology. 1983;19(1):131-139. doi:10.1111/j.1365-2265.1983.tb00751.x.
5. Ranabir S, Reetu K. Stress and hormones. Indian Journal of Endocrinology and Metabolism. 2011;15(1):18. doi:10.4103/2230-8210.77573.
6. Gandhi K. Approach to hypoglycemia in infants and children. Translational Pediatrics. 2017;6(4):408-420. doi:10.21037/tp.2017.10.05.
7. Mavroudis PD, Corbett SA, Calvano SE, Androulakis IP. Circadian characteristics of permissive and suppressive effects of cortisol and their role in homeostasis and the acute inflammatory response. Mathematical Biosciences. 2015;260:54-64. doi:10.1016/j.mbs.2014.10.006.
8. Goppelt-Struebe M, Wolter D, Resch K. Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase. British Journal of Pharmacology. 1989;98(4):1287-1295. doi:10.1111/j.1476-5381.1989.tb12676.x.
9. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Molecular and Cellular Endocrinology. 2011;335(1):2-13. doi:10.1016/j.mce.2010.04.005.
10. Tsigos C, Kyrou I, Kassi E, et al. Stress, Endocrine Physiology and Pathophysiology. [Updated 2016 Mar 10]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278995/