Cushing Syndrome and Endocrine Hypertension

The term Cushing syndrome (CS) denotes the signs and symptoms that result from having too much cortisol in the bloodstream for a long time. Cortisol is a steroid hormone produced by the adrenal glands. Some of the signs and symptoms of CS are weight gain (especially in the abdomen), rounded face, extra fat on the upper back and above the collarbone, reddish-purple stretch marks, easy bruising of the skin, high blood sugar (diabetes), and high blood pressure. In normal amounts, cortisol helps the body maintain blood pressure and cardiovascular function. But excessive cortisol can cause hypertension.

There are two types of CS—exogenous and endogenous. Exogenous means the cause is external to the body; endogenous means the cause is internal. Exogenous (external) CS is caused by taking medication containing glucocorticoids (cortisol-like medications) such as dexamethasone or prednisone. It goes away when the patient stops taking those medications.

Endogenous (internal) CS is caused by the body’s over-production of cortisol. It usually develops slowly and can be difficult to diagnose. The problem could be an adrenal gland tumor (usually noncancerous) that produces too much cortisol. More likely, it may be a pituitary gland tumor that produces too much adrenocorticotropic hormone (ACTH), the hormone that tells the adrenals to make cortisol. (The pituitary is a pea-sized gland located at the base of the brain that controls the function of other endocrine glands.) Rarely, a non-pituitary tumor can cause CS by secreting too much ACTH.  In patients with endogenous CS, hypertension is present in about 80 percent of adults and about half of children and adolescents.

Who should be tested for endogenous CS?
Certain patients should be tested for endogenous CS:

• Patients with unusual signs and symptoms for their age, e.g., osteoporosis (weak bones), high blood pressure, diabetes, or thin skin in younger patients.
  
  
• Patients with several and worsening signs and symptoms that suggest CS, e.g., reddish-purple stretch marks, rounded face, extra fat on the upper back and above the collarbone, and weight gain around the belly with relatively thin upper legs and arms.
  
  
• Children with poor height growth and increasing weight.
  
  
• Patients with a mass (tumor) on the adrenal gland detected by an imaging study.

Diagnosis of endogenous CS
Diagnosis is based on measurement of cortisol levels in the urine, saliva, or blood.

• Urine free cortisol (UFC) test measures the amount of cortisol in the urine over a 24-hour period.
  
  
• Late-night salivary cortisol measures the amount of cortisol in the saliva late at night.  Cortisol production is normally decreased at night, but in Cushing syndrome, this drop in production doesn’t occur.
  
  
• 1-mg overnight dexamethasone suppression test (DST) uses the glucocorticoid dexamethasone to suppress cortisol production. If cortisol levels do not drop, Cushing syndrome is suspected. For the overnight test, 1 mg of dexamethasone is taken late at night, and then blood is drawn the following morning to measure the cortisol level.
  
  
• Longer DST. Dexamethasone is given in doses of 0.5 mg for 48 hours at 6-hour intervals. This test better distinguishes CS from other conditions that can raise cortisol levels.

Treatment of endogenous CS
Surgery to remove the tumor is standard. For most patients surgery is successful, but some may also need radiation therapy or drugs to lower cortisol production. Most patients with CS can be successfully treated with excellent results.