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Cushing’s Disease vs. Cushing’s Syndrome—The Cortisol Connection, Complications and Cures

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Affecting only about 10 to 15 people per million every year, the rare condition, “Cushing Disease” can wreak havoc on the body, causing a multitude of uncomfortable and sometimes debilitating symptoms.[3] Cushing’s disease is different from Cushing’s syndrome, however.

Cushing Syndrome vs. Cushing Disease—What’s the difference?

Though sometimes mistakenly used interchangeably, Cushing’s syndrome and Cushing’s disease are two different diagnoses.

Cushing’s syndrome refers to the diagnosed medical condition of elevated levels of the hormone cortisol in the body. This encompasses all causes for the increased values.

In the case of Cushing’s disease, however, abnormal cells collect in the pituitary gland and form a tumor. This tumor releases excessive amounts of ACTH (adrenocorticotropic hormone). In direct response, the adrenal glands overproduce the hormone cortisol.

What are the symptoms of Cushing’s syndrome/disease?

Individuals with Cushing’s syndrome or Cushing’s disease may experience:

  • Weight gain/obesity in the torso
  • Marked fatigue
  • Weakness of muscles
  • High blood pressure
  • Ache in the back
  • High blood sugar
  • Bruising on the body 
  • Pronounced red stretch marks on the skin
  • Neurological problems[4]

Other Cushing’s disease symptoms may include:

  • A round face (moon face)
  • The hump on the back of the neck due to excess fat on the back of the neck
  • Thin arms and legs
  • Redness of face and cheeks
  • Diabetes 
  • Psychiatric issues[3]

Symptoms specific to women include menstrual cycle irregularities and facial/body hair growth.  Men may experience erectile dysfunction, low libido, and decreased fertility.[4]  

Complications Associated with Cushing’s Syndrome

Beyond the normal symptoms associated with Cushing’s syndrome, certain complications or other medical conditions may occur as a result.  

Some of these include:

  • Stroke
  • Heart attack
  • Blood clots (usually in the lungs or legs)
  • Infections
  • Fractures/loss of bone
  • High cholesterol 
  • Depression 
  • Mood disturbances
  • Difficulty concentrating
  • Loss of memory
  • Insulin resistance
  • Prediabetic conditions
  • Type 2 diabetes[5]

What is cortisol and why do we need it?

While excess cortisol in the body is unhealthy, cortisol in and of itself is not bad; in fact, it is necessary. Cortisol is a hormone, referred to as the “stress hormone” because it enables the body to respond appropriately to dangerous situations. Historically, the hormone was needed to keep individuals safe from physical harm from wild animals and other predators. Cortisol also helps the body convert food to energy, stabilize blood glucose and blood pressure, and keep inflammation down.

The adrenal glands, located on top of the kidneys, produce cortisol.

Who is likely to develop Cushing’s syndrome?

In general, Cushing’s syndrome affects adults aged 30-50, however in rare cases, children can develop Cushing’s syndrome as well.  While men may be diagnosed with the syndrome, women are three times more likely to have it.  Type 2 diabetics and those with high blood pressure are also more likely to develop Cushing’s syndrome than individuals without those conditions.[5]

Who gets Cushing’s disease?

Cushing’s disease is a rare disorder, affecting adults between the ages of 20 and 50.  Roughly 70% of the sufferers are women.[3]

Causes of Cushing’s Disease and Cushing’s Syndrome

Cushing’s disease develops when a pituitary tumor is present and releases excessive amounts of ACTH.  This stimulates the adrenals into overproducing cortisol.[1]

Cushing’s syndrome is much more common than Cushing’s disease and refers to consistently high levels of cortisol found in the body.                            

Types of Cushing’s syndrome and other causes include:

  • Exogenous Cushing’s Syndrome—Exogenous refers to something “outside” the body as the cause of Cushing’s.  Some medications such as glucocorticoids for inflammatory medical conditions can cause Cushing’s syndrome. 
  • Cushing Syndrome because of adrenal tumor—A tumor on one or both of the adrenal glands can cause the adrenals to produce too much cortisol.
  • Ectopic Cushing Syndrome—Ectopic Cushing’s syndrome occurs when ACTH is produced outside of the pituitary gland.  About 40-70 people per million are affected every year by this type of Cushing’s.[6]

Types of tumors that can possibly cause Ectopic Cushing syndrome include:

  • Lung tumor (benign carcinoid)
  • Pancreas tumor (islet cell)
  • Thyroid (Medullary carcinoma) 
  • Lung tumor (small cell)
  • Thymus gland tumor[6]

Persistent cortisol may exist if medications containing cortisol such as hydrocortisone, prednisone, skin creams, asthma medication, and steroid injections for joint pain are used.

Who takes steroids? —Why Cushing’s syndrome may result

Glucocorticoid steroids are contained in many medications and mimic the natural steroid hormones the body produces.  

Many medical conditions require steroid hormones to control inflammation in the body including:  

  • Asthma 
  • Rheumatoid arthritis
  • Lupus

Immune system suppression requiring glucocorticoid steroids may also be needed following organ or tissue implantation

Cushing's syndrome occurs when the body's tissues are exposed to high levels of cortisol for too long. 

How Cortisol Production Works

In healthy, normal individuals the hypothalamus, just above the brainstem sends CRH, or corticotrophin-releasing hormone to the pituitary gland located behind the nose.  This triggers the pituitary gland’s hyperproduction of adrenocorticotropic hormone (ACTH) causing the adrenal glands to flood the bloodstream with cortisol.  

Cortisol performs many necessary functions for the body and without it, we would cease to function correctly.  Cortisol is necessary to help the body keep blood pressure levels and help maintain cardiovascular function.  Cortisol also helps the body control the immune system and its inflammatory response and works to balance insulin in the body, needed for metabolic processes.[7] 

Who has abnormally high cortisol levels, naturally?

While glucocorticoid-steroid use is the most common reason for Cushing’s syndrome, higher-than-normal cortisol levels are also common among some individuals.  Cortisol levels may be high if you have depressive disorders, anorexia, or high estrogen levels.[3]

This further includes:

  • Trained athletes
  • Pregnant women in the last trimester of pregnancy (improves blood flow to the fetus)
  • Individuals with panic disorders
  • Individuals with depression
  • Malnourished individuals
  • Individuals with alcoholism[7]

How do doctors diagnose Cushing’s syndrome?

Cushing’s syndrome can be mistaken for other medical issues, so thorough examinations and testing are needed to rule out some conditions. Medications taken for inflammation (glucocorticoids) can also cause cortisol levels to soar.

Once this is done, a diagnosis is made by:

  • Thorough medical exam
  • Full patient history
  • Lab tests, including urine, saliva, and blood tests

Test measures may include:

  • 24-hour urine test
  • Late-night salivary cortisol test
  • Low-dose dexamethasone suppression test (LDDST)
  • Dexamethasone-CRH test
  • High-dose dexamethasone suppression test (HDDST).

Diagnosing Cushing’s Disease

A diagnosis of “Cushing's disease” refers solely to the state of elevated cortisol due to a tumor on the pituitary gland, where the hormone ACTH is produced and released.   

Cushing’s disease may be difficult to identify in some cases and should be diagnosed or confirmed by an endocrinologist. 

Once Cushing’s syndrome is confirmed, a doctor who suspects Cushing’s disease will run some or all of the following tests:

  • ACTH test
  • CRH stimulation test
  • CT Scan
  • MRI
  • Petrosal sinus blood draw along with blood drawn in another area of the body[5]

Treatment for Cushing’s Syndrome

keywords: cushing's syndrome symptoms,

Treatment for Cushing’s syndrome is dependent on the cause of increased cortisol levels.  

If this is due to corticoid-steroid medications, doctors may be able to reduce the dosage and manage an existing medical condition in other ways.  Causes involving the presence of tumors may be treated with surgery (or treatment to shrink the tumor). 

Some treatments include:

  • Surgery
  • Radiation
  • Chemotherapy
  • Reduction of glucocorticoid hormones (if taking)
  • Immunotherapy

Treatment for Cushing’s Disease

  • Endoscopic Pituitary surgery 
  • Transsphenoidal tumor removal (through the nose) has been successful for many Cushing’s disease patients
  • Radiosurgery
  • Bilateral Total Adrenalectomy
  • Drugs[7][2]

Whether you have some or all of the symptoms associated with Cushing’s syndrome or disease, it is critical to get a definitive diagnosis from an experienced physician who works with endocrine disorders.  Based on your complete medical history and the reason for Cushing’s finding, you can proceed with the best treatment option(s) available for your particular circumstances.


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