Cushing's disease, (a.k.a Cushing's syndrome and hypercortisolism ) is a rare, life-threatening, hormonal imbalance disorder.

Cushing's syndrome, also called hypercortisolism, is a rare endocrine disorder caused by chronic exposure of the body's tissues to excess levels of cortisol - a hormone naturally produced by the adrenal gland. Exposure to too much cortisol can occur from long-term use of synthetic glucocorticoid hormones to treat inflammatory illnesses. Pituitary adenomas (benign tumors of the pituitary gland) that secrete increased amounts of ACTH (adrenocorticotropic hormone, a substance that controls the release of cortisol) can also spur overproduction of cortisol."

Source : US NINDS (archived)

It was first described in 1910 (ref.) and has been widely researched.

The malfunction can be associated with :

• A pituitary tumor, which causes the pituitary gland (at the base of the brain) to stimulate the adrenal glands to secrete high levels of cortisol.
• A tumor of the adrenal gland (located above the kidney).
• A benign or malignant tumor of the lung or some other organ.
• Prolonged use of cortisone drugs, such as Prednisone, commonly prescribed for asthma, rheumatoid arthritis or lupus.

Source : Cushing's Support and Research Foundation

But exact biological mechanisms, i.e. why the tumores form, and how the triggers operate, remain unknown.

Possible links with genetic factors are also being investigated :

Cushing disease (CD) is a life-threatening disorder attributed to excess pituitary tumor-derived adrenocorticotrophic hormone (ACTH) and adrenal steroid secretion caused by pituitary tumors. Whereas CD was first described in 1932 ^{[ sic .? ]} the underlying genetic basis driving tumor growth and ACTH secretion remains unsolved."

Source : PNAS Biological Sciences, 110 (21) 8555-8560

Further detailed information : Cushing's Support and Research Foundation