Cushing's disease, (a.k.a Cushing's syndrome) is a rare, life-threatening, endocrine 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

(Note that genetic factors are also being investigated, see paper cited below)

But exact biological mechanisms, and how the triggers operate, remain unknown.

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