The Good, the Bad, and the Ugly
If you look around the pharmacy, you can find hydrocortisone in the skin care aisle, hemorrhoids aisle, and even in the first aid section. It is available in creams, gels, ointments, suppositories, and more. It is commonly used on the skin to treat rashes, itches, bug bites, inflammation, allergic reactions, swelling and minor discomfort. Because hydrocortisone is so readily available, many may be unaware hydrocortisone is a hormone with countless amazing functions and uses.
Early Hydrocortisone Research
In the mid-1930s researchers at the Mayo Foundation for Medical Education and Research began to focus on the hormones of the adrenal glands. While treating patients for rheumatoid arthritis, Dr. Philip Hench observed improvements in these patients’ conditions under circumstances such as pregnancy, surgery, estrogen and testosterone treatments, high fat diets, or even starvation. He theorized these circumstances might be connected with adrenal gland function.
Dr. Edward Kendall
Under the direction of Dr. Edward Kendall, adrenal hormones were extracted and crystallized, and were named in order of their extractions as Compounds A, B, C, D, E, and F. The first human patient treated for rheumatoid arthritis with injections of Compound E—which later would become known as “cortisone”—experienced dramatic relief. Treatment started on September 21, 1948, and within one week all symptoms of her disease disappeared. Other patients were treated with similar success. This work was so groundbreaking that, in 1950, Dr. Hench and his colleagues received the Nobel Prize in Medicine.
Compounds A through F were found to be made in the cortex of the adrenal gland. Like sex hormones, adrenal hormones are in the family of hormones called “steroids.” Compound F later became known as hydrocortisone, sometimes called cortisol. Although both cortisone and hydrocortisone are still used today, cortisone must be converted into the active form hydrocortisone to produce its effect. Hydrocortisone became the preferred treatment over cortisone.
Too Much of a Good Thing
While large doses of adrenal hormones allowed these early researchers to witness hydrocortisone’s dramatic results, these doses also produced a host of unwanted effects, such as weight gain, fluid retention, peptic ulcers, and increased incidence of infection. Additional adverse effects included developing a “moon face,” where fat buildup around the cheeks causes the face to appear round and puffy, thinning of the skin to the point of bruising or bleeding under the skin, and osteoporosis and bone fractures. These side effects were a poor tradeoff for treatment success.
A host of similar substances such as prednisone, prednisolone, methyl prednisolone, and dexamethasone were created in hopes of minimizing these complications. These synthetic substances proved to be just as problematic. Medical practitioners soon became wary of using any kind of “cortisone” therapy.
Dr. William McK. Jefferies
Working as an endocrinologist at Case Western Reserve in Cleveland, Dr. William Jefferies became convinced that the problems with using hydrocortisone and cortisone occurred when the dosing exceeded the amounts the human body normally produced. He claimed by using a “physiologic” dose, that the benefits of these hormones could be achieved and the alarming side effects avoided. In dosing “physiologically,” Dr. Jefferies mimicked the amounts of hormone produced and the timing of its release as closely as possible to that of the human body. Hydrocortisone became the focus of his 45-year career.
Dr. Thierry Hertoghe
Belgian physician Dr. Thierry Hertoghe continues where Dr. Jefferies left off, and points out three therapy errors in the original use of hydrocortisone that led to its long list of adverse effects.[iv]
- He echoes Dr. Jefferies in that the original dosing was simply too high and produced effects associated with Cushing’s Disease, the overproduction of hydrocortisone by the adrenal glands usually due to the presence of a tumor.
- Rather than treatment with a single hormone, complementary hormones should be given to achieve hormonal balance. In the body, there are hormones that stimulate the building (anabolism) of tissues and others that stimulate the break-down (catabolism) of tissues. Both are necessary to keep the body functioning as it should. Hydrocortisone and its derivatives are catabolic and cause the breakdown of tissue. Other adrenal hormones, like DHEA, balance the catabolic action of hydrocortisone, but these anabolic hormones were not used by early researchers.
- The catabolic action of hydrocortisone, as described in number 2 above, could also be counterbalanced by including appropriate amounts of protein in the diet, a detail not known in earlier research.
Functions of Hydrocortisone
Hydrocortisone has countless functions in the body. Dr. Hertoghe summarizes its main functions, particularly with regard to increasing energy and stress resistance. He notes that in adequately functioning adrenal glands, an increase in energy can be felt 3 to 15 minutes after hydrocortisone increases due to exposure to stress. Hydrocortisone increases energy in response to stress in a number of ways. It increases available glucose which the body uses to produce energy in the cells. It activates dopamine (a neurotransmitter hormone that increases energy and well-being) in the brain. It increases the supply of blood, oxygen, and nutrients to the brain and other tissues by increasing blood pressure. And it burns fat stores.
Dr. Hertoghe also explains the anti-inflammatory action of hydrocortisone is mediated through its effects on white blood cells and reducing collagen formation. Lastly, Dr. Hertoghe describes two little known effects of hydrocortisone; its antioxidant activity and its ability to break down fat.
While severe hydrocortisone deficiencies, such as Addison’s disease, are rare, mild adrenal deficiencies are widespread. Dr. Jefferies writes that the diminished production of hydrocortisone may be traced directly to the adrenal gland. Dr. Hertoghe describes hydrocortisone deficiencies where glands in the brain do not secrete enough of the hormones necessary to stimulate the adrenal glands. For example, the pituitary gland may not release enough adrenocorticotropic hormone (ACTH) or the hypothalamus may not release enough corticotropin-releasing hormone (CRH). Further complications may be due to issues with hydrocortisone receptors and with binding proteins. Dr. Hertoghe suggests testing for cortisol binding globulin (CBG) in women who have used birth control pills as they may have elevated levels of CBG. CBG can bind up hydrocortisone and make it unavailable for use by the body.
Major Symptoms and Signs
Those with low hydrocortisone will likely feel tired and have a lower capacity to respond to stress. Symptoms of low hydrocortisone may include flu-like feelings due to the generalized inflammation associated with low hydrocortisone. Low blood pressure and low glucose levels may cause a feeling of light-headedness, dizziness, and “foggy brain.” Allergies—including skin reactions and asthma—and sugar cravings may also be signs of hydrocortisone deficiency. When hydrocortisone levels are low, the adrenal glands may compensate by producing more adrenaline and noradrenalize (also known as epinephrine and norepinephrine). Symptoms of increased adrenaline and noradrenaline may include sweaty hands, feet and armpits; irritability and anxiety; jittery trembling of the hands; and rapid heart rate. Dr. Hertoghe also describes physical signs such as hollow cheeks, pigmented spots on the face, and dark circles under the eyes.
As mentioned above, low levels of hydrocortisone can lead to generalized inflammation. This can leave the body vulnerable to many conditions, including:
- Inflammations of the eyes, ears, and nose
- Skin rashes, eczema, and psoriasis
- Inflammation of the gastrointestinal tract resulting in colitis, gastritis, and enteritis (Note all “itis” endings of diagnoses words refer to inflammation)
- Allergies and asthma
- Arthritis and autoimmune diseases, such as lupus and even cancers
Dr. Jefferies identified low hydrocortisone levels in his patients struggling with infertility. He theorized that low hydrocortisone resulted in excessive estrogen and androgen production by the adrenal glands, which interfered with normal ovarian function. He also found out hydrocortisone and glandular thyroid supplementation decreased the incidence of miscarriage in women with repeated miscarriages. Treatment continued throughout the pregnancies without problems, and often was continued thereafter. Additionally, he found using hydrocortisone resolved acne and facial hair caused by polycystic ovary syndrome (PCOS), a condition often associated with infertility.
In men, Dr. Jefferies successfully treated patients with low sperm counts. Since sperm require 2 to 3 months to mature, he advised starting hydrocortisone treatment with that timing in mind.
Those with low hydrocortisone may lack enough of the enzyme histaminase to break down histamine. Excessive amounts of the hormone histamine can exist in tissues and cause runny noses, watery eyes, rashes, hives and itches, asthma, food allergies, and even anaphylaxis. Hydrocortisone can restore levels of histaminase needed to break down histamine and also inhibit the enzyme responsible for creating more histamine.
Many conditions fall under the heading of autoimmune disease. The similarity in each is the immune system malfunctions and attacks part of the body it should not. Dr. Jefferies reported success in using hydrocortisone to treat Grave’s disease, an autoimmune disease affecting the thyroid. He also recommended evaluation and treatment of adrenal deficiencies in people with diabetes, an autoimmune disease involving the pancreas, given the intimate relationship between hydrocortisone and blood glucose. Inflammatory diseases of the gut are often treated with prednisone, but Dr. Jefferies suggested low doses of hydrocortisone may be warranted. He also predicted that low dose hydrocortisone might be beneficial in multiple sclerosis, an autoimmune disease of the nervous system.
Resilience to infection is one of the most important aspects of adequate hydrocortisone levels and adrenal function. Without adequate hydrocortisone levels, individuals become more susceptible to bacterial, viral, and fungal infections. Dr. Jefferies routinely observed this in his patients.
In the case of bacterial infections, Dr. Jefferies recommended using antibiotics in conjunction with hydrocortisone. He felt viral infections like influenza could be avoided entirely in those already using hydrocortisone to treat adrenal insufficiency. If those using hydrocortisone did develop a viral infection, he suggested the course of the infection may be shortened and its intensity dampened by increasing the dose of hydrocortisone for a short period of time. In these cases, Dr. Jefferies would advise his patients to adjust their hydrocortisone dosing to address the infection just as the body would do by increasing their dose until the symptoms resolved, and then resuming their usual low dose.
Other Issues Associated with Hydrocortisone Deficiencies
Many more conditions may be related to underlying hydrocortisone deficiencies. Dr. Jefferies addressed some of these: hirsutism (inappropriate facial and body hair), acne (even including the more severe cystic types), severe menstrual cramping, and PMS. Hydrocortisone may play a role in treating low blood sugar, chronic fatigue, fibromyalgia, and jet lag.
Hydrocortisone may improve the utilization of thyroid hormone in those with thyroid resistance, a type of hypothyroidism when there are high levels of active thyroid in the blood, but the cells are not able to absorb it.
In the case of breast and prostate cancers, Dr. Jefferies believed high estrogen levels associated with these cancers may be provoked by low hydrocortisone levels and alleviated with hydrocortisone supplementation. In fact, he felt that all cancer patients should be evaluated for low hydrocortisone.
So what are the good, the bad, and the ugly sides to using hydrocortisone? The “good” is the multitude of uses of the adrenal hormone hydrocortisone in physiologic dosing as demonstrated by Dr. Jeffries. The “bad” occurs when crippling side effects occur with large doses. Hydrocortisone has even been designated “the death hormone” because high levels may be produced in response to unrelenting stress, which may have the same effect as excessive dosing. Eventually, however, the adrenal glands give up and deficiency problems ensue. The “ugly” is that medical practitioners have been ignoring this treatment for decades due to adverse effects seen at high doses.
Fortunately, research is still focusing on Dr. Jefferies’ ideas of physiologic dosing. Andrea Isidori and her colleagues at the University of Roma La Sapienza, demonstrated success with a modified release dosage form, continuing to honor the principles of physiologic dosing and timing.
The small doses of hydrocortisone Dr. Jefferies recommended were life-changing in his practice. He taught his patients how to increase their dosing in response to exceptional stress or infection, and return to their low maintenance dose once the crisis had passed. He found out that, unlike many other therapies and treatments, hydrocortisone is safe!
While physicians easily identify and treat the worst case scenarios of hydrocortisone deficiency, such as Addison’s disease, they often fail to take into account that our bodies don’t have just an “on and off” switch, but degrees of hydrocortisone deficiencies range from mild to life-threatening. It may take patience and determination to try to mimic the body’s natural hormonal output, but the effort is worthwhile as hydrocortisone treatments may be capable of miraculous results.
- Cooney WP 3rd. Compound F: The History of Hydrocortisone and Hand Surgery. J Hand Surg Am. 2013 Apr;38(4):774-8. doi: 10.1016/j.jhsa.2012.12.025. Epub 2013 Feb 9.
- Nobelprize.org. Philip S. Hench – Biographical. Nobel Media AB 2014. Web. 13 Mar 2013. https://www.nobelprize.org/nobel_prizes/medicine/laureates/1950/hench-bio.html.
- Jefferies WM. Safe Uses of Cortisol. 2nd Ed. Springfield, IL: Charles C. Thomas Publisher, LTD; 1996
- Hertoghe T. Cortisol Deficiency: Frequent, Life Impairing, and How to Give Patients Their Lives Back by Correcting It. Townsend Letter. 2018 Jan: 52-59.
- Jefferies WM et al. Low plasma levels of adrenocorticotropic hormone in patients with acute influenza. Clin Infect Dis. 1998 Mar; 26(3):708-10. https://www.ncbi.nlm.nih.gov/pubmed/9524849
- Isidori A, et al. Effect of once-daily, modified –release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomized controlled trial. https://www.ncbi.nlm.nih.gov/pubmed/29229498:1-13.