Charlotte, NC
Preeti Kharel
Dipendra Kandel, MD
Cushing’s syndrome occurs when the body is exposed to high levels of the hormone cortisol for an extended period. This can result from prolonged use of corticosteroid medications or, less commonly, from the body producing excess cortisol due to a tumor in the pituitary gland (Cushing’s disease), adrenal glands, or other body parts.
Typically, cortisol, a stress hormone, is produced from adrenal glands located on the top of each kidney. Cortisol is responsible for the flight and fight response. But when high, it causes Cushing’s syndrome. The annual incidence of Cushing’s syndrome ranges from 1.8 to 3.2 cases per million population.
Some of the common causes of cushing’s syndrome are:
This is the most common cause. If you take corticosteroid medications like prednisone for a long time, it can cause your body to have high levels of cortisol. These drugs often treat conditions like asthma, arthritis, or lupus. While they help control these illnesses, long-term use can lead to Cushing’s syndrome.
Sometimes, a small tumor can grow on your pituitary gland, which is located at the base of your brain. This tumor can cause your body to produce too much of a hormone called Adrenocorticotrophic Hormone (ACTH), which in turn causes your adrenal glands to produce more cortisol. This is the most common cause of Cushing’s syndrome when it happens naturally in the body and is called Cushing’s disease. It makes up about 60-70% of the cases.
Your adrenal glands can develop a tumor that directly produces extra cortisol. These tumors are usually not cancerous, but they can still cause your cortisol levels to spike. These benign tumors account for 0.6 million of the yearly incidence of Cushing’s syndrome.
In rare cases, tumors in other parts of your body, like your lungs or pancreas, can produce ACTH. This is called ectopic ACTH syndrome, as it is made outside of the body’s normal control system. These tumors are usually cancerous and cause your adrenal glands to make more cortisol, causing Cushing’s syndrome.
The most common symptoms of cushing’s syndrome are:
Too much cortisol in your body makes your body produce and store fat differently. You’ll notice that you gain weight mostly around your belly, face, and upper back, giving you a rounded face called moon face and a hump on your upper back called buffalo hump. You will probably start to see these changes slowly, with your face and trunk getting bigger first.
Excess cortisol in your body can make your skin thin and make it easy to bruise. It stops cells from making collagen, weakens blood vessels, and delays the healing of wounds. If you notice that you bruise easily, along with other skin changes like purple stretch marks and thinning skin, it could be a sign of Cushing’s syndrome.
In Cushing’s syndrome, your muscles weaken because high cortisol levels break down muscle proteins and prevent new ones from forming. This can even make it difficult for you to climb stairs, get up from chairs, or lift things easily.
An increased risk of fractures results from bone loss. It may have an overall sense of being poorly or feeling exhausted all the time. According to the 50% prevalence of osteoporosis, between 30 and 50 percent of individuals with CS suffer fractures, especially at the spinal level.
High cortisol levels in the body cause your kidneys to retain salt and water and raise the blood pressure.
Many people with this condition experience mood swings, irritability, and anxiety. Depression is particularly common, often presenting as persistent sadness, lack of interest in activities, and feelings of hopelessness. Some individuals may develop more severe psychiatric conditions, such as memory problems or cognitive decline. Sleep disturbances are also common, which can worsen feelings of fatigue and emotional instability. In rare cases, high cortisol can lead to psychosis, where individuals may experience hallucinations or delusions.
The diagnosis of cushing’s syndrome is made with the following tests:
In this test, you’ll collect your urine over a 24-hour period. The sample is then checked to see how much cortisol is in it. High cortisol levels in your urine can point to Cushing’s syndrome.
This test measures cortisol in your saliva late in the evening. Normally, cortisol drops after you fall asleep, but in Cushing’s syndrome, it doesn’t. You can collect your saliva sample at home and send it to a lab.
This is an important tool used to diagnose Cushing’s syndrome, and there are two types.
If the other tests suggest Cushing’s syndrome, imaging tests like a CT scan of the chest or MRI of the brain may be used to look for tumors in your pituitary or adrenal glands, which could be causing the excess cortisol.
Cushing’s syndrome treatment options:
If the syndrome is due to long-term medication use, your doctor will gradually lower your dosage or switch medications.
If Cushing’s syndrome is caused by a tumor, the most effective treatment is often surgical removal of the tumor. For pituitary tumors, this typically involves transsphenoidal surgery, where the tumor is accessed through the nose. If the tumor is in the adrenal gland, it may require laparoscopic surgery. In cases of ectopic ACTH syndrome, the tumor causing excess ACTH secretion is removed when possible. Temporary or life-long cortisol replacement therapy may be needed after surgery.
If surgery isn’t an option or is unsuccessful, radiation therapy may be used, either over several weeks or as a single high-dose treatment. This is more common for pituitary tumors. It can help shrink the tumor over time and lower cortisol production. Cortisol levels may take years to normalize after radiation so medications may be prescribed in the interim.
Several medications can help control cortisol production or control symptoms if surgery and radiation aren’t suitable.
Alongside medical treatments, lifestyle changes can help manage symptoms. This may include a healthy diet, regular exercise, salt restriction if you have high blood pressure, and stress management techniques to improve overall well-being and help combat the effects of high cortisol.
Cushing’s syndrome comes with several complications due to long-term high cortisol levels. These include:
The link between Cushing’s syndrome and Type 2 Diabetes Mellitus lies in the role of cortisol in glucose metabolism. In Cushing’s Syndrome, elevated cortisol levels trigger increased glucose production, insulin resistance, and impaired insulin secretion.
Cushing’s syndrome often causes metabolic syndrome, with symptoms like obesity, high blood pressure, abnormal cholesterol levels, and glucose problems, including diabetes. These issues raise the risk of heart problems like heart attacks and strokes.
Patients often have weak muscles and fragile bones, leading to a higher risk of fractures, especially in the spine.
High blood pressure, which is common in Cushing’s syndrome, increases the chances of heart issues and death from heart-related problems. Cushing’s syndrome also raises the risk of blood clots, increasing the likelihood of strokes and other clot-related issues.
Chronic high cortisol weakens the immune system, making people more prone to infections. This can lead to severe infections and even life-threatening conditions like sepsis.
In Cushing’s syndrome, excessive cortisol weakens your bones by slowing down bone formation, accelerating bone breakdown, disrupting calcium regulation, and causing hormonal imbalances. This can result in weaker bones and a higher risk of fractures despite appearing strong. Additionally, excess fat in bones and blood sugar issues further contribute to bone weakening.
Excessive hair growth in Cushing’s syndrome results from the overproduction of adrenal androgens, particularly in ACTH-dependent forms of the disease. This leads to hirsutism, a common manifestation in Cushing’s Syndrome patients.
High cortisol levels can disrupt menstrual cycles, cause infertility, impaired spermatogenesis, and lower sex drive by affecting reproductive organs and hormone levels.
