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Cortisol is a hormone necessary to mediate stress. Too much cortisol causes stress rather than alleviates it. In this lesson, we’ll talk about Cushing’s syndrome, when the body is exposed to too much cortisol over too long of a period of time.

The Cortisol Pathway

Everyone knows that there’s too much of a good thing. Even a cool glass of lemonade on a hot summer’s day can turn into a sticky mess if the person pouring it isn’t paying attention. We need the hormone cortisol to help us deal with stressful situations.

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In Cushing’s syndrome, the body experiences the effects of too much cortisol for too long of a period of time. The result? Cortisol, which usually mediates the effects of stress, instead ends up causing damage to the body.Cortisol is made by the adrenal glands, a pair of glands that rest on top of the kidneys. You can think of the steps of the cortisol pathway as a baseball player who runs the bases after hitting a home run. The pathway starts in the hypothalamus, the part of the brain responsible for much of the body’s ‘autopilot’ activity – things like breathing and heart rate. When the hypothalamus receives a stimulus that the body’s under stress, it releases corticotropin-releasing hormone (or CRH).

This speeds to the pituitary, where it tells the master gland to release adrenocorticotropic-stimulating hormone (or ACTH). ACTH races to the adrenal glands to release cortisol. Cortisol then goes on to do things like increase blood sugar levels, lower inflammation, and raise blood pressure.


Before we dig into what causes Cushing’s syndrome, we should clarify the relationship between Cushing’s syndrome and Cushing’s disease.

Remember that a syndrome is based on symptoms. It might help you to remember that ‘syn’ and ‘sym’ sound alike. A syndrome is different from a disease, which is a specific disturbance in a part of the body. Keep this in mind as we go through this part of the lesson. Cushing’s disease is just one cause of Cushing’s syndrome.

In other words, not all cases of Cushing’s syndrome are caused by Cushing’s disease.Cushing’s syndrome is also called hypercortisolism. ‘Hyper’ means high, sort of how we might get when we drink too much caffeine or eat too much sugar. Therefore, anything that causes the body to release too much cortisol can cause Cushing’s syndrome. Most medical professionals divide these causes into two large categories.The first is exogenous, meaning ‘generated from without.’ Long-term use of corticosteroid medications can cause Cushing’s syndrome.

Usually exogenous cases are also iatrogenic, caused by medical treatment. Corticosteroids are often prescribed for inflammatory diseases like arthritis or given by injection for pain. Cushing’s syndrome may develop if the dosage of medication is or becomes larger than the body can handle.The second large category is endogenous, meaning ‘generated from within.’ Endogenous cases of Cushing’s syndrome are usually caused by one of three things:

  • The first is a pituitary adenoma, a benign tumor of the pituitary gland. An adenoma may secrete large amounts of ACTH in a way that the body can’t control. A large amount of ACTH will stimulate the adrenal gland to produce a large amount of cortisol.

    Here, finally, we have the specific cause of Cushing’s disease. Roughly 70% of endogenous cases of Cushing’s syndrome are caused by pituitary adenomas and therefore are classified as actual cases of Cushing’s disease.

  • The second endogenous cause is called ectopic syndrome. You may recall that ‘ectopic’ means ‘in an abnormal place.’ Sometimes tumors of the lungs, pancreas, or thyroid release ACTH. Again, the body does not have the means to control this unplanned ACTH, and it stimulates the adrenal glands to produce too much cortisol.
  • The third endogenous cause is primary adrenal disease.

    In these cases, a tumor of the adrenal gland (again, usually benign) goes rogue and secretes large amounts of cortisol.

Symptoms, Diagnosis, and Treatment

Remember that cortisol gets us ready to face a stressful situation. What do we need when we’re stressed out? To name a few:

  • Increased blood sugar, especially in the brain.
  • Increase in blood pressure to get that energy circulating.
  • Drop in inflammatory response since there’s no sense wasting energy on fighting small infections.

  • Decrease in bone calcium, preparing that calcium to be ready for muscle contraction.

In Cushing’s syndrome, all of these actions happen, but there’s no reason. So you have too much cortisol being made not in response to stress and over a long period of time.

There’s a lot of symptoms for Cushing’s syndrome and they vary from person to person, so we’ll just focus on the classic ones from top to bottom:

  • Memory loss, since cortisol plays a role in brain function.
  • Weight gain and obesity, especially around the face (called ‘moon face’) and between the shoulder blades (called ‘buffalo hump’).
  • Osteoporosis and accompanying bone brittleness and fracture.
  • Thin, wrinkled, easily bruised skin, along with stretch marks that are pink or purple. Skin and wounds are also very slow to heal.
  • Hypertension (high blood pressure).

Because so many of these symptoms tend to be non-specific, laboratory tests are used for diagnosis. In general, physicians look for high cortisol in either the saliva or urine. Another test, called the dexamethasone suppression test, is also used in diagnosis. Dexamethasone is a drug that acts like cortisol. If the body has the ability to control cortisol production and is given this drug, then cortisol should decrease. In Cushing’s syndrome, though, cortisol production won’t decline.

The goal of Cushing’s syndrome treatment is to eliminate the excess cortisol. If the Cushing’s is exogenous, then treatment is a gradual reduction and/or replacement of cortisol drug therapy. Most endogenous cases of Cushing’s syndrome are treated by surgical removal or reduction of the pituitary adenoma or other type of tumor.

If cortisol production is very high, then cortisol-blocking medications, like mifepristone, can be used to control symptoms.

Lesson Summary

Cushing’s syndrome is defined as the group of symptoms that occur when the body is exposed to too much cortisol for too long of a period of time. Also called ‘hypercortisolism,’ Cushing’s syndrome can be exogenous – caused by administration of corticosteroid drugs. These cases are treated by gradual reduction and/or replacement of these medications. Some cases of Cushing’s syndrome, however, are endogenous – that is, caused by something within the body.Of endogenous cases, most are caused by pituitary adenomas that make ACTH, which, in turn, stimulates cortisol.

These cases are termed Cushing’s disease. Other endogenous cases are caused by ectopic syndrome, or tumors in unexpected places that release ACTH, and primary adrenal disease, tumors of the adrenal glands themselves. Treatment of these types of Cushing’s syndrome generally involve removal or reduction of the tumor.

Learning Outcomes

Watch this video lesson as you aim to reach these goals:

  • Describe Cushing’s syndrome
  • Outline the steps of the cortisol pathway
  • Recognize and categorize the causes of Cushing’s syndrome
  • State the effects of Cushing’s syndrome on bodily processes and point out the related physical symptoms
  • Relate ways in which Cushing’s syndrome is diagnosed and treated

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