Cushing’s Syndrome Mnemonic:
Cushing’s syndrome describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol. The most common cause of this is by taking glucocorticoid drugs, or diseases that result in excess cortisol, adrenocorticotropic hormone (ACTH), or CRH levels.
Cushing’s disease refers to a pituitary-dependent cause of Cushing’s syndrome: a tumor (adenoma) in the pituitary gland produces large amounts of ACTH, causing the adrenal glands to produce elevated levels of cortisol. It is the most common non-iatrogenic cause of Cushing’s syndrome, responsible for 70% of cases excluding glucocorticoid related cases.
Cushing’s Syndrome should not be confused with Cushing’s triad, a disease state resulting from increased intracranial pressure.
- Extreme weight gain
- Moodiness, irritability, or depression
- Muscle and bone weakness
- Diabetes mellitus
- Immune suppression
- Sleep disturbances
- Menstrual disorders such as amenorrhea in women and decreased fertility in men
Most Cushing’s syndrome cases are caused exogenous steroid medications (iatrogenic). Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication.
If the cause is due to adrenal adenoma then it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma’s location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.
In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid receptor antagonist has also rarely been used, but the medication faces considerable controversy due to its use as an abortifacient. In February 2012 the FDA approved mifepristone in order to control high blood sugar level (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women.
Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson’s syndrome.