Cushing’s disease overview
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Cushing’s disease is a disorder characterized by symptoms that include weight gain, changes in skin and body hair, and emotional disturbances. These symptoms develop due to excess production of the hormone cortisol.
Cushing’s disease is a specific type of Cushing’s syndrome, which is a broader term that encompasses any health problem where the symptoms are driven by high cortisol levels. Cushing’s disease is a specific form of the syndrome caused by a tumor in the pituitary gland.
What is Cushing’s disease?
A feature of Cushing’s disease is the excessive production of cortisol — a condition referred to as hypercortisolism. Cortisol is commonly called the stress hormone, because it’s made by the body during times of stress and helps activate the fight or flight response.
Cortisol helps control a wide range of processes: it affects how energy is used and fat is stored, regulates the activity of the immune system, helps control blood pressure and breathing, and is involved in processing emotions and forming memories.
Normally, levels of cortisol are tightly regulated, but in Cushing’s disease, these regulatory systems become dysfunctional, leading to the hormone’s excess production.
Other forms of Cushing’s syndrome also are marked by increased levels of cortisol, leading to symptoms like those seen in Cushing’s disease. The key difference is that Cushing’s disease is caused by a pituitary tumor, whereas in any other type of Cushing’s syndrome the underlying cause is something else.
Cushing’s disease is the most common form of endogenous Cushing’s syndrome, meaning cortisol levels are caused by problems inside the body. In contrast, exogenous Cushing’s syndrome typically results from side effects of medications.
Causes of Cushing’s disease
The pituitary gland is a pea-sized structure located toward the bottom of the brain. It’s responsible for secreting a variety of signaling molecules to coordinate the activity of several organs in the body and normally plays a key role in regulating cortisol.
Cushing’s disease is caused by a tumor in this gland. Pituitary tumors are usually small and benign, meaning the cancer itself doesn’t cause overt health problems. In Cushing’s disease, however, the tumor causes the pituitary gland to secrete abnormally high amounts of a signaling molecule called adrenocorticotropic hormone (ACTH).
ACTH triggers the adrenal glands — two small glands above the kidneys — to produce cortisol. In Cushing’s disease, high levels of ACTH lead to excess cortisol production in the adrenal glands. High levels of cortisol ultimately cause the symptoms of the disease.
Other forms of Cushing’s syndrome are characterized by excess cortisol levels, but are due to different causes, which may include:
- medications that increase cortisol activity
- tumors in locations other than the pituitary that make ACTH
- tumors in the adrenal glands that cause them to produce more cortisol.
Symptoms and complications of Cushing’s disease
Cushing’s disease can cause a wide range of symptoms, which usually develop gradually over time. Not everyone with Cushing’s will experience all the possible symptoms of the disease.
Common symptoms of Cushing’s disease include:
- weight gain
- fat buildup around the abdomen, in the face, and around the back of the neck and shoulder blades
- skin changes such as acne, darkened or thin skin, stretch marks, easy bruising, and poor wound healing
- balding of hair on the head
- growth of unusually thick, dark body hair
- emotional issues like irritability, depression, or anxiety
- fatigue
- low sex drive.
Cushing’s disease in men can cause erectile dysfunction and low sperm counts.
Cushing’s disease in women often causes irregular or absent menstrual periods. Women with the disease often have difficulty becoming pregnant and those who become pregnant are at increased risk of miscarriage or pregnancy loss.
Cushing’s disease in children can cause stunted growth, in addition to most of the symptoms seen in adults.
People with the disease are at increased risk of health complications, such as:
- weak and fragile bones
- diabetes
- high blood pressure (or hypertension)
- frequent infections
- cardiovascular problems including blood clots, heart attack, or stroke.
Diagnosis of Cushing’s disease
Diagnosing Cushing’s disease is a multi-step process. If a person is showing signs that indicate Cushing’s, the first step is usually to check for excess cortisol levels. Since cortisol normally fluctuates throughout the day, tests must be timed for optimal accuracy. Cortisol levels are typically lower at night. They may be measured by:
- urine tests, where urine is usually collected over 24 hours for testing
- saliva tests, on saliva collected late at night
- blood tests, done late at night.
If a person is found to have high cortisol levels accompanied by symptoms and signs of Cushing’s disease, this can confirm the broad diagnosis of Cushing’s syndrome. The next step to diagnosing Cushing’s disease specifically is testing to identify the underlying cause. This may include:
- blood tests to measure ACTH levels
- petrosal sinus sampling, where the blood vessels next to the pituitary are sampled to measure ACTH levels
- dexamethasone or corticotropin-releasing hormone tests, which involve administering a therapy that normally changes cortisol levels and then measuring to see if cortisol levels change abnormally, which can provide clues about whether cortisol levels are due to a pituitary tumor or another cause
- imaging tests, such as MRI, to look for a disease-causing tumor
Cushing’s disease treatment
A range of different treatments can be used for Cushing’s disease.
- Transsphenoidal adenomectomy, is a surgical procedure to remove the disease-causing tumor in the pituitary gland. It’s usually the first-line treatment for Cushing’s disease. Surgery can cure the disease in up to 90% of patients, especially when the pituitary tumor is small.
- Radiation therapy (also called radiotherapy) may be used to help destroy the pituitary tumor in patients who are not eligible for surgery or as a secondary treatment when surgery doesn’t completely remove the tumor.
- Chemotherapy is sometimes given to help destroy the pituitary tumor if it’s spreading or metastasizing to other parts of the body, but this is quite uncommon since most Cushing’s disease-causing tumors are benign.
- Medications that reduce cortisol levels are commonly given with therapies that target the tumor, such as surgery or radiotherapy. Cortisol-lowering medications also may be used as a first-line treatment when other therapeutic strategies, like surgery, aren’t good options. Several different medicines that can reduce cortisol are available such as Signifor (pasireotide), Korlym (mifepristone), Recorlev (levoketoconazole), and Isturisa (osilodrostat).
- Surgical removal of the adrenal glands, a procedure known as adrenalectomy, may be used to reduce cortisol levels in patients with persistent disease who haven’t responded to other treatments. Removing the adrenal glands can rapidly reduce cortisol levels, but necessitates lifelong treatment to replace hormones made by these glands, so this type of surgery is typically a last resort.
Also, lifestyle changes, such as eating a balanced diet, getting regular physical exercise, and avoiding alcohol and tobacco, may help managing Cushing’s disease and reduce the risk of other health problems associated with it.
How common is Cushing’s disease?
It’s estimated that Cushing’s disease affects 10 to 15 out of every million people worldwide. This number might be underestimated as people can go undiagnosed, however.
Cushing’s disease can affect anyone, but usually develops between the ages of 20 to 50 and is markedly more common in women. People with genetic conditions that increase the risk of cancers in hormone-producing glands may be at increased risk of Cushing’s disease.
Cushing’s disease prognosis
Without treatment, Cushing’s disease can be fatal. Most life-threatening problems in people with Cushing’s disease are not caused by the disease itself, but by related health complications that are common in these patients, such as uncontrolled diabetes, infections, or heart disease.
With appropriate treatment, Cushing’s disease can be curable, especially if the disease-driving tumor can be fully removed. In fact, one of the main factors that affect the prognosis of Cushing’s disease is whether the disease-causing tumor can be fully removed via surgery or other treatments.
Regarding life expectancy with Cushing’s disease, more studies are needed as some research has suggested that mortality rates in patients in remission are similar to those in the general population, while other studies have suggested that people with Cushing’s disease have an increased overall mortality rate. People with persistent or active disease have an increased mortality risk.
Available data indicates the risk of death due to Cushing’s disease is nearly twice as high in people who have persistent or recurrent disease after tumor removal, mainly due to cardiovascular disease and infection, compared with people who achieve long-term disease remission after initial treatment.
Other factors associated with higher mortality rates with Cushing’s include:
- older age at diagnosis
- a longer duration of high cortisol levels
- depression
- persistent cardiovascular issues such as diabetes or high blood pressure.
Even when initial treatments are successful, long-term monitoring for disease recurrence and other health problems is recommended with Cushing’s disease.
Cushing’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Cushing’s disease
Cushing’s syndrome is a broad term that refers to any health problem driven by excess levels of the hormone cortisol. Cushing’s disease is a specific form of the syndrome where high cortisol levels are the result of a tumor in the brain’s pituitary gland.
Cushing’s disease is caused by a tumor that forms in the pituitary gland, a small gland located in the base of the brain. The tumor causes the pituitary to secrete higher than normal levels of the signaling molecule adrenocorticotropic hormone (ACTH), which triggers excess cortisol to be produced in the adrenal glands. High levels of cortisol are the ultimate cause of Cushing’s symptoms.
While anyone can develop Cushing’s disease, the condition is more common in women than men and usually develops between the ages of 20 to 50.
Cushing’s disease is estimated to affect 10 to 15 out of every 1 million people worldwide. As many people can go undiagnosed, this number could be an underestimation, however.
Cushing’s disease can cause fatal complications if left untreated, but with appropriate care, life expectancy for someone with the disease is thought to be comparable to the general population. More studies are needed as there is some contradictory data regarding mortality rates in this patient population. Nonetheless, all evidence supports the fact that the prognosis for people with Cushing’s disease is typically better if the disease-driving tumor can be fully removed. Patients with persistent or active disease generally have an increased mortality risk.
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