Cushing’s Disease and Syndrome

Overview

Cushing's syndrome is caused by an inappropriate and chronic exposure to excessive levels of cortisol. The source of this excess of cortisol can be endogenous or exogenous (ie.medication).

When the excess of cortisol is caused by a pituitary adenoma (ie a tumor of the pituitary gland located in the brain), the condition of the patient is defined as Cushing’s disease.  Cushing’s disease represents 70% of the cases of endogenous Cushing’s syndrome.

Typical clinical features of Cushing’s syndrome may include central obesity with abdominal skin striae (but with thin arms and legs and proximal muscle weakness), fat pads buffalo hump, moon face, emotional instability and depression, severe fatigue and weakness, dyslipidemia, diabetes, hypertension and osteopenia. 

Because other conditions share the same signs and symptoms, Cushing’s syndrome can be difficult to diagnose (particularly endogenous Cushing’s syndrome), with a time to diagnosis of more than 6 years.
Cushing’s syndrome affects less than 1 in 10,000 people in the European Union, which is equivalent to fewer than 51,000 patients. Females are more frequently affected than males, and represents 75% of the Cushing’s syndrome population.

The well accepted treatment goal for patients is to normalize cortisol levels.  Typical treatments include surgery and/or medical interventions.  With proper treatment, the progression of the disease can be halted and symptoms reduced.

Diagnosis

The first step of Cushing’s syndrome diagnosis is to check the medications a patient takes. Then, the second step consists of a variety of tests, including: 

  • The measurement of urinary cortisol level that will show if the body is producing too much cortisol. Urine can be collected over a 24h period, 
  • Late evening saliva test: cortisol levels vary throughout the day. In people without Cushing’s syndrome, this level drops significantly in the evening. If this level is too high late at night, doctors might suspect a Cushing’s syndrome,
  • Dexamethasone suppression test (DST) is also typically used to diagnose Cushing’s syndrome and consists in the measurement of cortisol level in the blood after taking Dexamethasone.

Symptoms

Patients with Cushing’s syndrome may develop the following signs and symptoms, which can vary from one patient to another:

  • Rapid weight gain, 
  • Central obesity,
  • Emotional instability and depression,
  • Severe fatigue and weakness,
  • Osteopenia (low bone density),
  • Dyslipidemia (blood lipid levels that are too high or low),
  • Moon face (medical sign in which the face develops a rounded apparence), 
  • Hirutism (ie excessive facial or body hair growth),
  • Striae,
  • Buffalo hump,
  • Irregular menstruation in women,
  • Acne.

Causes

Cushing’s syndrome can have either endogenous or exogenous origin.

Endogenous Cushing’s syndrome is due to an excess in cortisol production. In normal conditions, ACTH (adrenocorticotropic hormone) is secreted by the pituitary gland to stimulate the release of cortisol from the adrenal glands (located above the kidney).
There are 3 different causes of endogenous Cushing’s syndrome:

  • In pituitary Cushing’s, also known as Cushing’s Disease, a pituitary adenoma induces an excessive production of ACTH, leading to an increased production of cortisol, and this represents 70% of endogenous Cushing’s syndromes,
  • In adrenal Cushing’s, the increased production of cortisol is caused by an adrenal gland tumor,
  • In diseases such as small cell lung cancer, ACTH can be produced outside the pituitary-adrenal system and affect the production of cortisol.

Exogenous Cushing’s syndrome (or iatrogenic) is caused by the use of glucocorticoids (for instance Prednisone) to treat other diseases (like asthma).