WHAT IS IT?
Cushing syndrome is a broad term that refers to increased glucocorticoid levels within an individual. This can be caused by a variety of different reasons including:
- Exogenous source of glucocorticoids (such as over-prescription of steroids such as prednisone).
- Cushing disease: an adrenocorticotropic hormone (ACTH)-secreting tumor in the pituitary gland.
- An ectopic (outside of the pituitary) ACTH secreting tumor (such as small cell carcinoma of the lung)
- A corticosteroid-secreting tumor of the zona fasciculata (middle zone) of the adrenal gland.
*Cushing disease is a specific type of ACTH secreting tumor that causes Cushing syndrome.
WHY IS IT A PROBLEM?
An excess of ACTH will result in increased glucocorticoid levels because ACTH stimualtes corticosteroid release from the adrenal glands. Given that glucocorticoids are responsible for a wide variety of physiological processes (explained more in the “HY Fact” section of this page) having an excess can lead to a wide variety of physiological issues that will be explained in more detail below. Generally speaking excess cortisol is responsible for some of the issues experienced, because it causes fat and protein catabolism, which ultimately raises blood sugar levels. This in turn will cause increased insulin levels within the body that can result in fat deposition in certain regions (face, trunk, etc.).
WHAT MAKES US SUSPECT IT?
Risk factors: long-term steroid use,
Vital signs: high blood pressure
Physical exam findings:
Round face: also referred to as “moon facies”, patients who have Cushing syndrome will often have roundly shaped faces with puffiness and facial redness.
Central obesity: patients will preferentially gain adipose tissue around their trunk/stomach region.
Striae: These are reddish/purple stretch marks that can be found on the buttocks, thighs, and stomach.
Hirsutism: This is a term for unwanted male-pattern hair growth on a woman’s face, chest, and back.
Buffalo hump: fat deposits in the back of the of shoulders/neck.
Muscle weakness/thin extremities: cortisol causes the breakdown of muscle for gluconeogenisis.
HOW DO WE CONFIRM A DIAGNOSIS?
*Because there are so many causes of Cushing syndrome, diagnostic testing must be tailored to specific patient cases. That being said most diagnostic paths will begin with analyzing levels of glucocorticoids (simply because this is the definition of Cushing syndrome).
24 hour-urine cortisol measurement: exactly as it sounds, patient urine will be collected for 24 hours and the levels of cortisol will be measured. Upper range of normal is 110-138 nmol/day (40-50 mcg/day, source). Multiple measurements should be taken (2 or more) given sensitivity of the test and the possibility of missing intermittent hypercortisolism.
Serum ACTH measurement: if it is established that cortisol levels are elevated, it is useful to uncover if this finding is ACTH dependent. If the ACTH is elevated then it very likely is the cause of the high glucocorticoid levels, and an ACTH secreting tumor is implicated (either in the pituitary or in an ectopic location).
Dexamethasone suppression test: administration of dexamethasone (a cortisol analogue) should in high doses provide negative feedback to an ACTH recreating pituitary tumor (an ectopic/paraneoplastic tumor will not have the proper mechanisms in place of ratios negative feedback). It should be noted that transformed cells in the pituitary typical won’t respond to low doses of dexamethasone (so a low dose suppression test will not be able to distinguish between ACTH recreating tumor types).
HOW DO WE TREAT IT?
*Treatment for Cushing syndrome will depend upon its underlying cause
Surgical removal of causal tumor is a common treatment option (although irradiation is also a possible means of treating tumors).
Pasireotide is a somatostatin analog that is used for the treatment of Cushing disease.
HOW WELL DO THE PATIENTS DO?
*The prognosis for patients with Cushing syndrome will depend upon its underlying cause
Cushing disease: 20-year survival reported to be about 87% (source)
WAS THERE A WAY TO PREVENT IT?
Causes of Cushing syndrome due to overuse of steroid medications are preventable. Avoiding prescribing corticosteroids for long periods of time is generally a good practice however the pros and cons of each clinical decision needs to be assessed on an individual basis.
WHAT ELSE ARE WE WORRIED ABOUT?
Osteoporosis: excessive glucocorticoids will cause increases in bone resorption and decreases in bone formation (source) which ultimately can cause brittle/fragile bones in patients.
Acanthosis nigricans: this is a skin condition caused by epidermal hyperplasia, hyperpigmented thickening of the skin that is found often around the neck or axilla/armpit. This is associated with hyperinsulemia which patients with Cushing can have due to elevated blood sugar levels (caused by increased glucocorticoid levels).
OTHER HY FACTS?
Corticosteroids are a class of steroid hormones that are responsible for regulating a wide variety of processes including: inflammation, the stress response, immune response, regulation of inflammation, carbohydrate metabolism, protein breakdown, serum electrolyte levels, cognitive function, and behavior.
Glucocorticoids are a specific type of corticosteroids that can control carbohydrate, fat, and protein metabolism. They also are responsible for preventing inflammation. A good example of a glucocorticoid is cortisol.
ARCHIVE OF STANDARDIZED EXAM QUESTIONS
This archive compiles standardized exam questions that relate to this topic.
Page Updated: 01.01.2016