How Glucocorticoids Affect Human Health

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By Katherine Araque, MD, and Ricardo Correa, MD, Es.D
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Glucocorticoids (gloo/ko/KORD/ih/coids) are a group of fascinating hormones in the human body. The main glucocorticoid is cortisol. Cortisol is the “stress hormone” produced by the adrenal glands, which are located above the kidneys. Cortisol has multiple actions including support of glucose synthesis, inhibition of inflammatory and immune responses, inhibition of bone formation and increase of bone resorption, maintenance of muscle function, modulation of emotional tone, and others.

Glucocorticoids are medications widely used for allergic, autoimmune conditions, and adrenal insufficiency, and have an important therapeutic role in various cancers. They were first isolated in 1948 as extracts of animal adrenal glands. Over time, development of various routes of administration, lower costs and prolonged half-life compounds have made them more suitable for human use. This year, glucocorticoids are the ninth most common prescribed medication among different specialties in the United States, according to GoodRX. And it’s easy to see why. The American Autoimmune Related Disease Association’s report for March 2019 estimates that 50 million Americans have an autoimmune disease. Additionally, the Department of Health and Human Services’ Office of Women’s Health states that autoimmune disease and disorders ranked #1 in a top ten list of most popular health topics.

Below is a list of glucocorticoids available in clinical practice, classified by how they are given to patients and their generic names. You can see that synthetic glucocorticoids can play an important role in management of various ailments. However, it’s important to understand both their benefits and adverse effects on your body.

Oral Intravenous Inhaled Topical
Prednisone Hydrocortisone Budesonide Betametasone
Prednisolone Metylprednisolone Beclomatasone Cortisone
Methylprednisolone   Fluticasone Triamcinolone
Dexamethasone   Mometasone  
Hydrocortisone      

Benefits

At higher dosages, glucocorticoids suppress inflammation. At lower dosages, glucocorticoids can provide pain relief and improvement of joint stiffness. Patients should discuss with their healthcare providers the individual benefits and risks while receiving treatment with glucocorticoids, even if a short treatment course is prescribed. The goal in glucocorticoid therapy is to use the smallest effective dose for the shortest period of time.

Adverse Effects

The adverse effects of glucocorticoid therapy are related to their potency, mechanism of action, individual differences in steroid metabolism and timing of dosing. Higher dosages and prolonged courses will increase the risks of adverse reactions. Glucocorticoids’ short-term side effects include a higher risk of widespread infections, clot formation in the extremities or the lungs, and bone fractures.

These adverse effects, particularly in long-term synthetic glucocorticoid use, can affect several organs and even be life-threatening. The most common organs and systems affected are in the table below.

Cardiovascular system Increased blood pressure by increasing the sodium retention in the body and stimulation of chemical substances that cause blood vessel contraction. High cholesterol levels, thrombosis and vasculitis.
Eyes Glaucoma, cataracts and serous leakage of the choroidal vessels in the retina, which can lead to visual loss.
Musculoskeletal system Muscle atrophy, most commonly in the muscles proximal to the torso, delayed growth in children, osteoporosis in adults and fractures can present at any age.
Skin & adipose tissue (fat) Weight gain can be present in up to 70% of cases and is the most frequently reported adverse effect, increased abdominal fat accumulation, fat pads in the back, above the collar bones and rounded face. Facial redness, skin thinning, easy bruising, delayed wound healing, acne, excessive hair growth, spider veins and purple stretch marks on the abdomen or extremities.
Reproductive system Delayed puberty, low testosterone and estrogen levels, which could lead to infertility.
Nervous system and mood Changes in behavior, memory loss, atrophy of the brain cortex, hallucinations, emotional liability, insomnia.
Gastrointestinal system Increased risk of bleeding, development of stomach ulcers, inflammation of the pancreas.
Kidneys Increased sodium retention leading to water retention and low potassium levels that can lead to muscle cramping or arrhythmias.
Immune system Increased risk of infections and activation of latent viruses.
Endocrine system Diabetes mellitus, thyroid problems, inability of the body to produce its own cortisol (known as secondary adrenal insufficiency), and permanent need of glucocorticoids to prevent critical illness and death.

Additional adverse effects can occur when prolonged glucocorticoids are prescribed in conjunction with other therapies like proton pump inhibitors, such as omeprazole (acid reflux medication), due to their intrinsic mechanism of action and adverse effect profile.

"The best strategy when deciding if you will benefit from glucocorticoids is to discuss available and effective alternative treatment options with your healthcare provider."

The best strategy when deciding if you will benefit from glucocorticoids is to discuss available and effective alternative treatment options with your healthcare provider. When glucocorticoids are prescribed judiciously, healthy lifestyle patterns will help decrease some of their adverse events. Patients receiving glucocorticoids should continue to perform physical activity, make healthy food choices, receive physical therapy as clinically indicated, and use prophylactic treatments to prevent infections (including pneumonia and influenza immunization). Additionally, prophylactic treatment with calcium, vitamin D and medications that will improve the bone loss caused by these agents is recommended. Close monitoring of glucose and blood pressure levels should be discussed with your health care team before starting therapy.

Despite more than 70 years of investigation and clinical experience with the use of glucocorticoids, uncertainties about development of side effects and monitoring still exist. The potency of these drugs to decrease inflammation guarantees their continued use. Development of new agents that block the inflammation pathway without causing the glucocorticoid-related side effects has a tremendous potential to advance the medical field.