How the ‘stress hormone’ cortisol contributes to Cushing syndrome
July 19, 2024
Cortisol is a hormone that’s essential to life, but it has developed a bad reputation due to its association with stress. A hormone made by the adrenal glands, cortisol is responsible for coordinating important body processes such as:
- Converting fat, carbohydrates, and proteins into energy.
- Controlling blood pressure and the cardiovascular system.
- Regulating the immune system.
- Responding to stress.
But when the body releases too much cortisol over time, you may be at increased risk of health problems such as osteoporosis, Type 2 diabetes, and heart and metabolic conditions. In some cases, patients develop Cushing syndrome, a condition associated with excess cortisol.
Cushing syndrome is a common side effect of chronic exposure to synthetic glucocorticoids, also called exogenous Cushing syndrome, when symptoms are caused by taking glucocorticoids. These include medications such as prednisone, methylprednisolone, and dexamethasone, which act like cortisol in the body. Glucocorticoids can be given as oral tablets, injections, topical creams, or inhalers. Occasionally, glucocorticoids can be found in herbal preparations and over-the-counter medicines.
Rare cases can occur when the body makes too much cortisol, known as endogenous Cushing syndrome – a rare endocrine condition that develops as a result of a pituitary, adrenal, or neuroendocrine tumor.
In February 2024, comedian Amy Schumer shared that she had been diagnosed with Cushing syndrome, citing high-dose steroid medications as the cause (such as exogenous Cushing syndrome). Ms. Schumer said public commentary on swelling of her face tipped her off that something was wrong.
Other symptoms of Cushing syndrome can include:
- Acne.
- Bone loss.
- Depression, anxiety, and irritability.
- Easy bruising from thin, fragile skin.
- Excess hair growth on the upper body (women).
- Fatigue and sleep disturbance.
- Frequent infections.
- Headaches.
- Irregular or ceased menstrual periods.
- Muscle loss and weakness.
- Purple stretch marks on the skin of the abdomen, arms, breasts, and thighs.
- Weight gain with fatty deposits in the face, midsection, shoulders, and upper back.
All of these symptoms can easily be mistaken for other common and serious conditions, such as cancer and polycystic ovary syndrome (PCOS). Patients often see multiple providers over several months or years before getting the right diagnosis and treatment. At the UT Southwestern Endocrinology Division, our multidisciplinary experts understand how to diagnose, treat, and cure Cushing syndrome while managing the underlying causes of your high cortisol levels.
"Elevated cortisol levels are a sign that something is wrong in the body, and getting the right diagnosis can allow for reversal of high cortisol levels by addressing the underlying condition."
What causes Cushing syndrome?
In the U.S., only 10 to 15 people per million are diagnosed with Cushing syndrome each year, and most are women 20 to 50 years old – ages when people are generally healthy and may not immediately recognize vague symptoms.
Most often, exogenous Cushing syndrome is related to long-term use of corticosteroid (glucocorticoid) medications, which treat inflammatory conditions such as asthma and rheumatoid arthritis and suppress the immune system after an organ transplant. Corticosteroids act like a stress hormone in the body and can raise cortisol levels high enough to cause Cushing syndrome.
In rare cases, Cushing syndrome can be caused by an adrenal, pituitary, or neuroendocrine tumor. These tumors can be benign or malignant. Tumors can cause the body to release too much cortisol or adrenocorticotropic hormone (ACTH), which regulates cortisol production.
Sometimes high cortisol levels can be associated with untreated, chronic inflammatory conditions such as diabetes, alcohol use disorder, obesity, or PCOS. Elevated cortisol levels are a sign that something is wrong in the body, and getting the right diagnosis can allow for reversal of high cortisol levels by addressing the underlying condition.
How is Cushing syndrome diagnosed and treated?
An endocrinologist with experience in treating Cushing syndrome is key to getting an accurate diagnosis and an effective treatment plan.
Having high cortisol levels does not immediately indicate Cushing syndrome. Some patients, especially those with unmanaged chronic conditions, may have hypercortisolism, which is excessive cortisol but not Cushing syndrome. Over time, hypercortisolism can increase your risk for heart disease, inflammation, and a weakened immune system.
To diagnose Cushing syndrome:
- An endocrinologist will gather your comprehensive health history, including past and current health conditions and medications.
- If the specialist suspects elevated cortisol, he or she will order tests of your blood, urine, and/or saliva to check your cortisol level.
- Additional dynamic tests, such as dexamethasone suppression test or desmopressin stimulation test, may be needed to confirm the diagnosis.
- If these tests show excess cortisol, the next step is to measure ACTH level to determine the cause of Cushing syndrome (pituitary/neuroendocrine or adrenal).
- After confirming endogenous Cushing syndrome, a CT or MRI scan is done to locate tumors responsible for Cushing syndrome.
Treatment for Cushing syndrome depends on the underlying cause. Stopping the use of corticosteroids can cure Cushing syndrome, but that is not safe for every patient and should not be done abruptly. When corticosteroids are necessary, such as for treatment of kidney inflammation, the care team will watch for signs of diabetes, high blood pressure, and osteoporosis and focus on managing side symptoms of excess cortisol.
When someone abruptly stops corticosteroid medications, the body may have a hard time producing cortisol. This is called adrenal insufficiency, and it can cause symptoms including severe weakness, confusion, low blood pressure, and unconsciousness, so it’s important to work with an endocrinologist to manage this transition.
Patients with Cushing syndrome caused by a tumor may need minimally invasive surgery to remove the tumor or affected gland. After surgery, patients may need lifelong medication to replace their cortisol and other hormones.
On the forefront of understanding cortisol imbalance
As CT and MRI technology improve and providers order more scans, we are finding a higher number of adrenal gland tumors. Our research has shown these tumors are often associated with mild autonomous cortisol secretion, or mild hypercortisolism that is not severe enough to cause overt Cushing syndrome, but can still increase metabolic risks such as diabetes, hypertension, and bone loss.
About 5% of the population has these tumors, and 20%-50% of people with adrenal tumors can have mild hypercortisolism. Patients with these tumors and mild autonomous cortisol secretion have a higher risk of:
- Diabetes.
- High blood pressure.
- Heart disease.
- High cholesterol and triglycerides.
- Low bone density.
UTSW is a high-volume endocrinology center, which means we see more patients with rare conditions than most community centers. Our data show that surgery to remove the adrenal gland can help these patients return to normal levels of cortisol.
The stress hormone cortisol may have developed a bad reputation, but stress is a part of life – and cortisol release is a normal response to it. When your cortisol level is in balance, it’s vital to helping the body run smoothly. But if you have signs that your cortisol level is too high, talk with an endocrinologist who has expertise in Cushing syndrome to get an accurate diagnosis and an effective treatment plan.
To talk with an expert about cortisol or Cushing syndrome, call 214-645-8300 or request an appointment online.
