What is Cushing's syndrome?
It often results from using medications that lead to high levels of cortisol in the body, but other causes include a benign or cancerous tumor.
People sometimes confuse Cushing's syndrome with Cushing's disease. The two are related but not the same.
In Cushing's disease and Cushing's syndrome, a number of factors can lead to high levels of the hormone cortisol. This, in turn, leads to a number of symptoms.
In Cushing syndrome, too much cortisol in the body results in a range of symptoms.
One cause of Cushing's syndrome is Cushing's disease. This is a rare condition that happens when a pituitary adenoma — a non-cancerous tumor in the pituitary gland — releases high levels of a hormone known as adrenocorticotropic hormone (ACTH).
These high levels of ACTH trigger high levels of cortisol, resulting in a range of symptoms.
Sometimes, the tumors form because of certain genetic changes or syndromes. Most of the time, it is unclear why it happens.
Genetics Home Reference note that it usually appears in adults between the ages of 20 and 50 years, but it can affect children, too.
Statistics suggest it affects about 10 to 15 people per million globally.
Seven out of 10 people with Cushing's disease are women.
Cushing's syndrome includes Cushing's disease, but it most commonly happens when the use of steroid medications affects hormone levels.
Apart from those with Cushing's disease, people who are at risk of developing Cushing's syndrome include those who:
- take large doses of steroid medication for another illness, such as asthma
- have a tumor in the adrenal gland
- have cancerous tumors that produce ACTH, for example, certain lung cancers
All of these factors can lead to a high level of cortisol in the body.
Less commonly, tumors develop in other organs that release ACTH, leading to similar symptoms.
When Cushing's syndrome happens for reasons that are not drug-linked, 70 percent of these cases will be due to Cushing's disease, according to the American Association of Neurological Surgeons (AANS).
Pseudo-Cushing's syndrome is when symptoms are similar to those of Cushing's syndrome, but further tests show that the syndrome is not present. Common causes include consuming too much alcohol, obesity, persistently high blood glucose levels, pregnancy, and depression.
How does it happen?
The pituitary gland produces hormones. If a tumor develops on this gland, Cushing's symptoms may result.
The body system that controls hormone production is the endocrine system.
Within this system, the glands work together and produce different types of hormones.
The hormones that one gland produces can directly affect the hormone production of other glands.
These glands include the adrenal glands, pituitary gland, thyroid gland, parathyroid glands, pancreas, ovaries, and testicles.
The adrenal glands are just above the kidneys. They produce cortisol, along with other hormones. Cortisol is the primary stress hormone, and it is the major natural glucocorticoid (GC) in humans.
Cortisol helps to regulate how the body turns proteins, carbohydrates, and fat from food into energy.
It also helps to control blood pressure and blood glucose levels and to maintain cardiovascular function. It can suppress the immune system, and it affects how the body responds to stress.
When cortisol levels are persistently high, Cushing's syndrome can result.
Genetic factors may play a role in some cases, but Cushing's syndrome and Cushing's disease do not appear to run in families.
There are two types of Cushing's syndrome.
Exogenous Cushing's syndrome
Exogenous Cushing's syndrome is when the cause comes from something outside the body's function.
It often results from long-term, high-dose usage of corticosteroid drugs, also known as glucocorticoids. These are similar to cortisol.
Steroid medications that do not appear to increase the risk of Cushing's syndrome are:
- steroid creams, a treatment option for eczema
- inhaled steroids, a treatment for asthma
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) note that over 10 million people in the United States use glucocorticoid medications each year, but it remains unclear how many develop the symptoms of Cushing's syndrome.
Endogenous Cushing's syndrome
Endogenous Cushing's syndrome is when the cause comes from inside the body, for example, when the adrenal glands produce too much cortisol.
Cushing's disease is an example of this.
Similar symptoms can also result from adrenal gland tumors or from a benign or malignant tumor in the pancreas, thyroid, thymus gland, or lung.
These, too, may result in an overproduction of cortisol.
Cushing's syndrome can affect different parts of the body. Symptoms may vary widely among individuals, depending on the cause.
Weight gain is a key symptom. High levels of cortisol result in a redistribution of fat, especially to the chest and stomach, along with a rounding of the face. A "buffalo hump" may develop as fat accumulates on the back of the neck and shoulders.
Other common signs and symptoms include:
- a thinning of the skin
- excessive pink or purple stretch marks known as striae
- easy bruising
- high blood pressure
- muscle weakness
- interruption or changes in menstrual periods
Limbs may be thin, compared with the rest of the body, and the face becomes puffy, rounded, and red.
Cushing's syndrome can affect the skin in the following ways:
- The skin becomes thin.
- It bruises easily.
- Reddish-purplish stretch marks can appear on the stomach, buttocks, limbs, and breasts.
- Spots can develop on the shoulders, chest, and face.
- Darkened skin appears around the neck.
- Edema, or water retention, occurs within the skin.
- Minor injuries take longer to heal, such as grazes, cuts, scratches, and insect bites.
Women may have excessive facial and body hair, known as hirsutism. A woman's voice may deepen, and she may lose the hair on her head. Menstruation may become irregular and less frequent, and it may stop completely.
The muscles in the shoulders, limbs, and hips may weaken, and the high levels of cortisol can lead to osteoporosis, or brittle bones, increasing the risk of fractures.
Changes in mental health can occur, possibly leading to:
- anxiety and depression
- loss of emotional control
- extreme mood swings
- panic attacks
- thoughts of suicide
Sexual problems include a lower libido, or sex drive. A man may have erectile dysfunction, which is the inability to achieve or sustain an erection.
Cushing's symptoms can affect fertility in both women and men. However, if the adrenal glands overproduce testosterone and other hormones too, this may increase libido.
According to the NIDDK, other problems and complications can include:
- high blood pressure
- blood clots, stroke, and heart attack
- unhealthy cholesterol levels
- types 2 diabetes and insulin resistance
- increased thirst, more frequent urination, and profuse sweating
Other complications include:
- a higher risk of life-threatening blood infections and other unusual infections
- kidney stones
- loss of muscle mass and strength
- changes in mental function
In children, Cushing's syndrome can result in obesity and a slow growth rate, according to the NIDDK.
Anyone who is taking corticosteroid drugs for conditions such asthma, arthritis, or inflammatory bowel disease (IBD), and who experiences the signs and symptoms of Cushing's syndrome, should tell their doctor as soon as possible.
Other conditions and diseases can have similar symptoms, so it is important to eliminate these first.
If the doctor thinks there may be a hormonal problem, they will probably refer the person to an endocrinologist, a specialist in the body's hormonal system.
Tests to assess the levels of ACTH may include:
- a urine test
- a blood test
- a saliva test
If a doctor suspects Cushing's syndrome, they will ask for more tests — for example, MRI imaging tests — to investigate the cause. These tests may detect an underlying tumor, whether benign or malignant.
Sometimes an inferior petrosal sinus sampling (IPSS) test may be necessary. This is a specialized blood test that, along with other tests, can help identify the source of ACTH in the body.
While waiting for the results, the doctor may prescribe metyrapone. This blocks the production of cortisol and lowers its concentration in the blood.
If the use of steroid medication triggers the symptoms of Cushing's syndrome, the doctor may need to change the dose or prescribe a different drug.
Treatment aims to find the source of the excess cortisol and reduce its levels.
The type of treatment will depend on several factors, including the cause of the syndrome.
If tests show that the person has Cushing's disease, they may need to undergo surgery to remove the pituitary tumor.
If a person has Cushing's symptoms because they are using corticosteroids to treat a health condition, the physician may reduce the dose of the drug, or replace it with a non-corticosteroid medication.
Individuals should never lower their corticosteroid dosages without medical supervision. This could lead to dangerously low levels of cortisol and possibly life-threatening complications.
Some people may need surgery to remove a pituitary tumor. A surgeon can remove a tumor through the person's nose. Tumors in the adrenal glands, pancreas, or lungs may need either conventional or laparoscopic surgery.
After surgery, the person will need to take cortisol replacement drugs until normal hormone production returns.
Drugs that currently have approval for treating Cushing's syndrome include mifepristone (Korlym) and pasireotide (Signifor).
Doctors may prescribe other medications off-label.
This means that a drug does not have approval specifically for this condition, but experience by doctors has shown that these medications are effective for the condition.
Drugs that people can take off-label for Cushing's include:
- ketoconazole (Nizoral)
- mitotane (Lysodren)
- metyrapone (Metopirone)
These can help to control the excessive production of cortisol in various ways. Research continues into other medications which may also be helpful.
A surgeon may need to remove the adrenal gland if no other treatment works.
Cushing's syndrome and Cushing's disease are serious conditions. Without treatment, they can be fatal.
However, if a person has a proper diagnosis in good time, surgical or medical treatment can enable them to return to a healthier life.
Lifelong follow up is important to reduce the risk of possible complications and improve the person's quality of life.