Cushing syndrome is a condition caused by prolonged exposure to abnormally high levels of cortisol, a hormone your adrenal glands produce to regulate metabolism, immune response, and your body’s reaction to stress. Endogenous Cushing syndrome (caused by something inside the body) is rare, affecting roughly 0.7 to 2.4 per million people each year. The most common form, however, comes from an external source: long-term use of prescription steroid medications.
How Cortisol Works in a Healthy Body
Your body produces cortisol through a chain of signals. The hypothalamus, a small region in the brain, releases a hormone that tells the pituitary gland (just below it) to release another signaling hormone into the bloodstream. That second signal travels to the adrenal glands, which sit on top of your kidneys, prompting them to produce cortisol. Once cortisol levels rise high enough, the brain detects this and dials back the signals, creating a natural feedback loop that keeps levels in check.
Cortisol follows a daily rhythm, peaking in the morning and dropping at night. It also surges during physical or emotional stress. About 95% of cortisol in the blood is bound to carrier proteins, and only the small free portion enters cells to do its work, influencing everything from blood sugar and blood pressure to how your body stores fat and fights infection. Cushing syndrome develops when something breaks this feedback loop or floods the body with cortisol from outside.
What Causes Cushing Syndrome
The single most common cause is taking synthetic glucocorticoid medications, such as prednisone, for weeks or months at a time. These drugs are prescribed for chronic conditions like asthma, rheumatoid arthritis, and inflammatory bowel disease. Because they mimic cortisol, high doses over long periods produce the same effects as having too much of the body’s own hormone. This is called exogenous Cushing syndrome.
When the cause originates inside the body (endogenous), doctors classify it by whether the problem involves the signaling hormone from the pituitary gland or not:
- Pituitary tumors (Cushing disease): A small, usually noncancerous tumor on the pituitary gland overproduces the signal that tells the adrenal glands to make cortisol. This specific subtype is called Cushing disease and accounts for the majority of endogenous cases.
- Ectopic tumors: Tumors elsewhere in the body, most often in the lungs, can produce the same signaling hormone. Lung tumors of a type called bronchial neuroendocrine tumors account for about 25% of these cases, with small-cell lung carcinoma responsible for roughly 19%.
- Adrenal tumors: A tumor on one or both adrenal glands can produce excess cortisol on its own, bypassing the brain’s feedback system entirely. These can be benign (adenomas) or cancerous (carcinomas).
It’s worth noting the naming distinction: “Cushing syndrome” is the umbrella term for any cause of excess cortisol, while “Cushing disease” refers specifically to cases driven by a pituitary tumor.
Recognizable Physical Changes
Cushing syndrome reshapes the body in distinctive ways. Fat redistributes to specific areas: the face becomes round and full (sometimes called “moon face”), a pad of fat builds up between the shoulders (“buffalo hump”), and fat accumulates above the collarbones. Meanwhile, arms and legs may actually become thinner as muscle wastes away.
The skin shows telltale signs too. Wide, purple or reddish stretch marks, often more than half a centimeter across, appear on the abdomen, buttocks, thighs, breasts, and under the arms. These are different from the pale, thin stretch marks that come with weight gain or pregnancy. The skin becomes fragile and bruises easily, and wounds heal slowly. Many people develop acne, and women may notice increased facial or body hair.
Other common symptoms include persistent fatigue, muscle weakness (especially in the thighs and upper arms), mood changes like anxiety or depression, difficulty sleeping, and irregular menstrual periods in women. Weight gain, particularly around the midsection, is one of the earliest and most noticeable changes.
How It’s Diagnosed
Because many symptoms of Cushing syndrome overlap with common conditions like obesity, depression, and polycystic ovary syndrome, diagnosis typically requires multiple tests to confirm that cortisol levels are genuinely elevated.
Three first-line screening tests are used. The overnight dexamethasone suppression test is the most common: you take a 1 mg pill of dexamethasone (a synthetic steroid) between 11 PM and midnight, then have your blood drawn the next morning between 8 and 9 AM. In a healthy person, the pill signals the brain to stop cortisol production, so morning levels drop. If your cortisol stays above 1.8 mcg/dL, the feedback loop isn’t working normally, which raises suspicion for Cushing syndrome. That cutoff catches about 95% of true cases.
The other two tests are a 24-hour urine collection (measuring all the cortisol your body excretes over a full day, with values above 135 nmol/L considered elevated) and a late-night salivary cortisol test (cortisol should be at its lowest late at night, so a value above 1.7 nmol/L is abnormal). Doctors usually require at least two abnormal results before moving forward, because a single test can produce misleading results from stress, illness, or certain medications.
Once excess cortisol is confirmed, additional blood tests and imaging (MRI of the pituitary, CT of the adrenals, or CT of the chest) help pinpoint the source.
Health Risks of Prolonged High Cortisol
Left untreated, Cushing syndrome does real damage over time. Excess cortisol pulls calcium from bones, leading to osteoporosis and fractures, sometimes in areas like the spine or ribs that don’t typically break from minor trauma. It raises blood pressure and blood sugar, increasing the risk of hypertension and type 2 diabetes. It suppresses the immune system, making infections more common and harder to fight off. Cardiovascular disease is the leading cause of death in people with untreated Cushing syndrome, driven by the combination of high blood pressure, elevated blood sugar, and abnormal cholesterol levels.
Cognitive effects are also significant. Many people experience memory problems, difficulty concentrating, and emotional instability that can be mistaken for primary psychiatric disorders.
Treatment Options
Treatment depends entirely on the cause. If the problem is prescription steroid use, the solution is gradually tapering the medication under medical supervision. Stopping suddenly can be dangerous because the adrenal glands, suppressed by the external steroids, need time to resume normal cortisol production.
For pituitary tumors (Cushing disease), surgery through the nose to remove the tumor is the first-line treatment. This approach achieves remission in roughly 71% to 80% of cases. The challenge is that recurrence is common, ranging from 5% to 50% after initially successful surgery, with about half of recurrences showing up within the first four years. Patients need long-term follow-up with periodic cortisol testing even after a successful operation.
When surgery isn’t possible or doesn’t fully resolve the problem, several medications can help control cortisol levels. Some block the enzymes the adrenal glands use to manufacture cortisol. Others target the pituitary gland to reduce the overactive signaling. A third type blocks cortisol from binding to its receptors throughout the body, neutralizing its effects even though blood levels remain high. Radiation therapy directed at pituitary tumors is another option, though it typically takes months to years to reach full effect.
For adrenal tumors, surgical removal of the affected adrenal gland is usually curative when the tumor is benign. Adrenal cancers require a more aggressive approach combining surgery with medications that have both cortisol-blocking and antitumor properties.
Recovery and What to Expect
After successful treatment, recovery is gradual. The adrenal glands often need months, sometimes over a year, to start producing normal amounts of cortisol again. During this period, you may need replacement cortisol tablets and will likely feel fatigued, achy, and generally unwell as your body adjusts to normal hormone levels. This withdrawal phase can be discouraging because it sometimes feels worse than the disease itself.
Physical changes reverse at different speeds. Weight redistribution and facial fullness improve over several months. Muscle strength returns with activity, though rebuilding lost bone density can take longer. Stretch marks fade but rarely disappear completely. Mood and cognitive symptoms generally improve within the first year, though some people report lingering effects on memory and emotional regulation even after cortisol levels normalize.