Hyperadrenocorticism, also known as Cushing’s syndrome or Cushing’s disease, is a disorder that develops when the body is exposed to too much of a hormone called cortisol over an extended period. This condition can significantly affect many aspects of daily life, from physical appearance to emotional wellbeing, and requires careful medical attention and ongoing management.

Understanding the Numbers: Who Gets Hyperadrenocorticism

Hyperadrenocorticism is relatively uncommon in humans, though precise numbers vary depending on the source. Research suggests that somewhere between 40 and 70 people out of every million are affected by this condition each year.^[3][6] This means that while you might not encounter many people with this disorder in everyday life, it affects thousands of individuals when we look at larger populations across entire countries.

The condition shows clear patterns in who it affects most commonly. Women are diagnosed with hyperadrenocorticism approximately three times more often than men.^[3] Some sources suggest that as many as 70% of people with this syndrome are women, while only about 30% are men.^[6] The condition typically appears in adults, with most diagnoses occurring in people between the ages of 25 and 50, though it can affect individuals of any age, including children and teenagers.^[3][6]

There is also a form of hyperadrenocorticism that affects dogs, which occurs much more commonly in veterinary medicine than in human medicine. In dogs, the condition predominantly affects middle-aged to older animals, typically between 7 and 12 years old.^[2] Among dogs with naturally occurring hyperadrenocorticism, approximately 85% have the pituitary-dependent form, while 15% have an adrenal tumor causing the problem.^[2] Certain breeds are more susceptible, including Poodles (especially Miniature Poodles), Dachshunds, Boxers, Boston Terriers, Yorkshire Terriers, and Staffordshire terriers.^[2]

What Causes This Condition

Hyperadrenocorticism develops when the body has excessive amounts of cortisol, but the underlying reasons for this excess can vary. Understanding these causes helps healthcare providers determine the best approach to treatment. The root cause always involves either the body producing too much cortisol on its own, or receiving too much cortisol-like medication from external sources.

The most common cause of hyperadrenocorticism is actually taking glucocorticoid medications, which are medicines that affect the body in the same way as cortisol.^[1][3] More than 10 million Americans take glucocorticoids each year, though not all develop this syndrome.^[3] These medications are prescribed to treat many conditions, including chronic asthma, rheumatoid arthritis, and other autoimmune diseases.^[6] When someone develops hyperadrenocorticism because of taking these medicines, doctors call it “exogenous” Cushing’s syndrome, meaning it comes from outside the body.^[6]

When the body itself produces too much cortisol without medication being the cause, this is called “endogenous” hyperadrenocorticism, meaning it originates from within the body.^[3] The most frequent internal cause is a small growth, usually non-cancerous, developing on the pituitary gland near the brain.^[7] This tiny tumor continuously signals the adrenal glands to produce cortisol, even when the body doesn’t need it. When a pituitary tumor causes the problem, doctors specifically call this Cushing’s disease, which accounts for more than 70% of adult cases and about 60% to 70% of cases in children and adolescents.^[6]

Another internal cause involves a tumor growing directly on one of the adrenal glands themselves. The adrenal glands are two small glands that sit on top of each kidney, and they normally produce cortisol in response to signals from the pituitary gland.^[3] When a tumor develops on an adrenal gland, it may produce cortisol independently, ignoring the usual control mechanisms. These adrenal tumors can be either benign (non-cancerous) or malignant (cancerous).^[7]

Risk Factors: Who Is More Vulnerable

Understanding who faces higher risk for developing hyperadrenocorticism helps both patients and doctors stay vigilant. The single largest risk factor is taking glucocorticoid medications for extended periods, particularly at high doses.^[6] People prescribed these medicines for conditions like chronic asthma, rheumatoid arthritis, lupus, or other autoimmune disorders need to be monitored carefully for signs of developing too much cortisol in their systems.

Gender plays a significant role in risk, with women being substantially more vulnerable than men to developing hyperadrenocorticism. The reasons for this gender difference aren’t completely understood, but the pattern holds consistently across different studies and populations.^[3][6]

Age is another factor, with most cases appearing in middle-aged adults. People between 25 and 50 years old face the highest risk, though the condition can develop at any age, including in children and elderly individuals.^[3][6] In people who have type 2 diabetes along with blood glucose levels that remain too high over time and high blood pressure, hyperadrenocorticism may be an underlying cause worth investigating.^[3]

Recognizing the Symptoms

The symptoms of hyperadrenocorticism develop gradually, often over months or even years, which can make the condition difficult to recognize at first. Because the symptoms come on slowly, many people and even their doctors may not immediately connect them to a single underlying problem. The excessive cortisol affects many different body systems, leading to a wide range of symptoms that can significantly impact quality of life.

One of the most noticeable changes is weight gain that occurs in specific patterns. People with hyperadrenocorticism typically gain weight in their trunk, face, and upper back, while their arms and legs may actually become thinner.^[1][6] The face often becomes rounder, sometimes described as a “moon face,” and a fatty deposit may develop between the shoulders, sometimes called a “buffalo hump.”^[1][6] The abdominal area may develop a “potbelly” appearance.^[2]

Skin changes are very common and can be quite distressing. The skin becomes thinner and more fragile, bruising much more easily than before.^[1][6] Distinctive pink or purple stretch marks often appear on the stomach, hips, thighs, breasts, and underarms.^[1][6] Wounds and cuts heal more slowly than normal, and acne may develop or worsen.^[1] Some people also experience increased skin infections.^[2]

Muscle weakness is another significant symptom, particularly affecting the muscles at the top of the arms and legs.^[7] This weakness can make everyday activities like climbing stairs, getting up from a chair, or lifting objects more difficult. Along with the weakness comes persistent fatigue and lethargy that doesn’t improve with rest.^[2]

Changes in thirst, urination, and appetite are very common. Many people find themselves constantly thirsty and drinking much more water than usual. This increased thirst leads to urinating more frequently and in larger amounts.^[2] Appetite often increases significantly, leading to eating more food, which contributes to the weight gain.^[5]

Women may experience specific symptoms including irregular menstrual periods or periods stopping completely, along with excessive hair growth on the face and body, a condition called hirsutism.^[1] Both women and men may notice a decreased interest in sex.^[7]

Emotional and mental changes can be just as challenging as physical symptoms. People with hyperadrenocorticism often experience mood swings, feeling irritable, anxious, or depressed.^[1][6] Some individuals report difficulty concentrating or memory problems.^[6] These emotional symptoms can significantly affect relationships, work, and overall quality of life.

Prevention: Can It Be Avoided

For hyperadrenocorticism caused by the body’s own production of too much cortisol due to tumors, there are no known prevention methods. These tumors develop for reasons that aren’t fully understood, and currently, there’s no way to prevent them from forming. However, for the most common form of hyperadrenocorticism—that caused by taking glucocorticoid medications—careful medical management can significantly reduce risk.

When doctors prescribe glucocorticoid medications, they try to use the lowest effective dose for the shortest time necessary to treat the underlying condition.^[7] If you need to take these medications, work closely with your healthcare provider to monitor for any signs of developing too much cortisol in your system. Regular check-ups can help catch problems early, before they become severe.

Never adjust the dose of glucocorticoid medications on your own. If you’re concerned about side effects or believe you might be taking too much, discuss these concerns with your doctor. They can evaluate whether your dose needs adjustment or whether alternative treatments might be appropriate for your underlying condition. Sometimes doctors can prescribe the medication in different ways, such as using creams or inhalers instead of pills, which may reduce the risk of developing hyperadrenocorticism.

If you’ve been taking glucocorticoid medications for a long time, learn the warning signs of hyperadrenocorticism so you can report them to your doctor promptly. Early detection makes treatment more effective and can prevent serious complications from developing. Your healthcare team should monitor you regularly if you’re on long-term glucocorticoid therapy.

How the Body Changes: Understanding Pathophysiology

To understand what happens in hyperadrenocorticism, it helps to know how cortisol normally works in the body. Cortisol is often called the “stress hormone” because your body releases extra amounts during times of stress.^[6] It serves many essential functions: it helps maintain blood pressure, regulates blood sugar, reduces inflammation, helps form memories, manages breathing, balances salt in the body, and transforms food into energy.^[3][6]

The production of cortisol involves a carefully coordinated system involving three parts of the body. The hypothalamus, a part of the brain, communicates with the pituitary gland, also in the brain, which then controls the adrenal glands sitting on top of the kidneys.^[6] Normally, this system works through a feedback loop: when cortisol levels get high enough, the adrenal glands signal back to the pituitary gland to stop producing ACTH (adrenocorticotropic hormone), the hormone that tells the adrenal glands to make cortisol.^[5]

In hyperadrenocorticism, this feedback mechanism breaks down. If a tumor grows on the pituitary gland, it continuously produces ACTH regardless of how much cortisol is already in the bloodstream.^[5] The adrenal glands respond by producing more and more cortisol, leading to persistently elevated levels. This results in both adrenal glands becoming enlarged because they’re constantly being stimulated.^[5]

If instead a tumor grows on one of the adrenal glands itself, that gland produces cortisol independently without waiting for signals from the pituitary gland.^[5] In this situation, the affected adrenal gland becomes enlarged while the other gland may actually shrink because the high cortisol levels suppress the normal signaling pathway.

When cortisol remains too high for too long, it affects nearly every organ system. It breaks down muscle tissue, leading to muscle weakness and thinning of the arms and legs.^[1] It affects how the body stores fat, causing the characteristic redistribution of weight to the face, neck, and trunk.^[6] Excess cortisol weakens the skin’s structure, making it thin and fragile, and interferes with wound healing.^[1]

The hormone affects bone metabolism, increasing the risk of osteoporosis and fractures.^[6] It raises blood pressure and can lead to heart problems.^[6] Cortisol interferes with how the body processes sugar, often leading to high blood glucose levels and potentially causing type 2 diabetes or prediabetes.^[6] The immune system becomes suppressed, making infections more common and harder to fight off.^[2]

In the brain, excessive cortisol affects mood regulation and cognitive function, contributing to the anxiety, depression, irritability, and memory problems that many people with hyperadrenocorticism experience.^[6] These changes in brain chemistry help explain why emotional symptoms are such an important part of this condition and why people often feel significantly better emotionally once cortisol levels are brought under control.