Cushing Syndrome

Cushing’s syndrome is named after the Yale neurosurgeon, Harvey Cushing, who first described it. In this syndrome, patients have too much cortisol or steroids in their blood. Cortisol is a hormone produced by the adrenal glands. 

Adrenal glands are located just above each kidney and are part of the endocrine system. One function of the adrenal glands is to produce hormones called catecholamines, such as epinephrine and norepinephrine. Cortisol is a hormone produced by the outer layer (cortex) of the adrenal glands and helps the body respond to stress. Primarily, cortisol increases blood sugar, suppresses the immune system, aids in fat, protein, and carbohydrate metabolism, and helps control the amount of water in the body. In controlled amounts, it is necessary to sustain life, maintain normal sleep-wake cycles and to aid the body’s responses in stressful situations. 

When too much cortisol is produced, serious and significant changes can occur that affect a person’s appearance and health. This collective set of changes and corresponding symptoms is referred to as Cushing’s syndrome.


Causes of Cushing Syndrome

Cushing's syndrome is a disease caused by an excess of cortisol production and is often caused by an adrenal tumor overproducing glucocorticoids. When the level of cortisol in the body is too high, a person may develop Cushing's syndrome. 

When a person’s body is making too much cortisol, there are three main reasons: 
  • Pituitary: the pituitary is a small gland at the base of the brain. It is often called the master gland of the endocrine system. If the pituitary gland secretes too much adrenocorticotropic hormone (ACTH), it can cause the adrenal glands to become hyperactive and make too much cortisol. In 70 percent of cases, a pituitary gland tumor is the cause of excess ACTH production. When the pituitary gland is the cause of Cushing’s syndrome, the condition is actually called “Cushing’s disease.” 
  • Adrenals: tumors located in one of the adrenal glands can also cause the adrenals to become hyperactive, producing too much cortisol. In about 30 percent of cases, an adrenal tumor is the cause of Cushing’s syndrome.
  • Other “ectopic” source: In 1 percent of cases, ACTH syndrome causes Cushing’s syndrome. A tumor lying outside of the pituitary gland is making too much ACTH. Most commonly, these ectopic sites are cancerous tumors often located in the lung or thymus gland. 
The cause of Cushing’s syndrome is divided into two types: those that are ACTH-dependent and those that are ACTH-independent. As the name suggests, cases that are ACTH-dependent are caused by the overproduction of ACTH. In ACTH-independent cases, the adrenal glands are overproducing too much cortisol even though ACTH levels are low. 

Cushing’s syndrome can also be caused by prescription medications similar to cortisol (steroids) in high doses over a long period of time. Such medications may be prescribed for rheumatoid arthritis, asthma, and inflammatory bowel disease. These medications are also common for transplant patients to help prevent the immune system from attacking the organ transplant.


Risk Factors

A risk factor is anything that increases a person's chance of getting a disease. Different diseases have different risk factors. Some risk factors can be controlled with lifestyle changes. Other risk factors cannot be changed.

Some risk factors associated with developing Cushing’s syndrome include:
  • A pituitary gland tumor 
  • An ectopic ACTH-secreting tumor (when a tumor develops in an organ that normally does not produce ACTH, the tumor will begin to secrete this hormone in excess) 
  • A primary adrenal gland disease Benign, nodular enlargement of both adrenal glands Familial Cushing's syndrome (an inherited form of Cushing’s syndrome) 
Having one of the above risk factors does not mean that you will develop Cushing Syndrome. Understanding your risk factors will help you determine, what, if any, precautions and possible screening options you should consider.


Symptoms

Signs and symptoms of Cushing's syndrome include: 
  • Weight gain – particularly around the gut or mid-section 
  • "Moon face" – a rounded shape of the face that develops from a specific pattern of fat distribution.
  • Easy bruising – the arms and legs are frequently covered with multiple bruises. 
  • "Buffalo hump" – a mound of fat at the base of the back of the neck. 
  • Abnormal hair growth – women with Cushing's syndrome may develop more hair growth on the face or near the belly button. 
  • Edema (leg swelling) – due to excess fluid buildup in the lower legs and feet. 
  • Stretch marks (purple striae) – most common around the sides and lower abdomen, these may have a pink, red, or purple color. 
  • Hypertension (high blood pressure) 
  • Diabetes (high blood sugar levels) 
  • Mood changes – many patients feel "hyper" while others may experience sudden emotional ups and downs or be quick to anger. 
  • Thinning of the skin – the skin may develop a shiny, paper-thin quality and may rip or tear easily. 
  • Ruddy complexion (plethora) – a reddening of the face or cheeks. 
  • Muscle weakness – the arms and legs may become skinny like twigs from muscle wasting. 
  • Menstrual disturbances – a woman's period may be irregular or stop altogether. 
Some of the above symptoms are non-specific and can occur as a result of other conditions, such as obesity or the polycystic ovarian syndrome (PCOS). Overall, Cushing's syndrome is a very rare cause of weight gain. In other words, most weight gain that occurs in the United States is a result of diet and exercise behaviors, and not Cushing's syndrome. Of the above signs and symptoms, the ones that are most specific to (indicative of) Cushing's syndrome are easy bruising, muscle weakness, and ruddy complexion. Patients who have too much cortisol but do not have any clear signs or symptoms of hypercortisolism are said to have "subclinical Cushing’s."

If you have Cushing’s syndrome, you may experience any of the following physical symptoms: 
  • Thinning and weakness of the muscles of the upper arms
  • Weight gain, especially on the face, abdomen, neck, and upper back
  • Thinning of the skin
  • Easy bruising
  • Pink and purple stretch marks 
  • Increased acne
  • Facial hair growth and scalp hair loss in women
  • Ruddy complexion
  • Darkening skin on the neck 
  • Obesity and poor growth in height in children 
Other symptoms may include: 
  • High blood pressure 
  • Fatigue 
  • Weakness 
  • Depression 
  • Mood swings 
  • Increased thirst and urination 
  • Ceased menstrual periods 
Having one or more of the above symptoms does not mean that you have Cushing’s syndrome. This list should be used as a guideline only. 

Many people who have classic symptoms of Cushing’s syndrome may actually have another condition, such as polycystic ovary syndrome, ovarian tumors, congenital adrenal hyperplasia, or obesity. 

If you think you have Cushing’s syndrome, please contact your doctor. If left untreated, Cushing's syndrome will cause continued weakening of the muscles, fatigue, poor skin healing, weakening of the bones and spine, and a suppressed immune system.


Treatment

If a tumor in the adrenal gland is the cause of the Cushing’s syndrome, surgery to remove the affected adrenal gland, known as an adrenalectomy, is the preferred treatment option. Removing the affected adrenal gland generally reverses any symptoms caused by the tumor. If both adrenal glands need to be removed, then patients will need to take medications to replace the hormones that would normally be excreted by the adrenal glands.

Surgical Treatment
Adrenalectomy
In a traditional adrenalectomy, an incision is made over the abdomen or side in order to provide direct access to the adrenal gland. A laparoscopic adrenalectomy requires smaller incisions. During a laparoscopic procedure, three to four half-inch incisions are made, and surgeons use a camera for visual guidance and special instruments to remove the adrenal gland or glands. With a laparoscopic adrenalectomy, most patients go home within 24 to 72 hours and experience minimal pain and a shorter recovery time than patients who have a traditional adrenalectomy. 

The majority of our adrenalectomies are performed using laparoscopic methods.

At Yale Endocrine Surgery, our multidisciplinary team is highly experienced in the surgical treatment of pheochromocytomas. Our surgeons are specially trained in both traditional and laparoscopic techniques. Before any procedure, our surgeons will answer all your questions and address all your concerns so that you feel comfortable with what to expect. 

Non-Surgical Treatment
Some patients may not be able to have their tumors treated surgically because of the way it is growing or if it is cancerous and has spread to other parts of the body. In these cases, the patient should work with their endocrinologist to determine the best course of treatment.