Physiopathology of Cushing's Disease

HARVEY CUSHING first described a patient with the disease bearing his name in 1912 (1). The patient manifested rapidly acquired central obesity, hypertrichosis, amenorrhea, and muscle weakness; on physical examination, “her round face was dusky and cyanoid,” supraclavicular and posterior cervical fat pads were present, and it was also noted that the skin was rough and dry, with considerable pigmentation, and with numerous ecchymoses and purplish striae. At that time, Cushing was uncertain as to whether the symptoms were attributable to pituitary “or adrenal, pineal, or ovarian influences,” involvement of these regions having previously been reported in association with similar clinical findings. There was apparently an even earlier report of a similar clinical syndrome by Osier in 1899 (2), which was described, however, as “An acute myxoedematous condition, with tachycardia, glycosuria, melaena, mania, and death” (the latter occurring within 6 months of onset). Between 1923 and 1926, in addition to other case reports, there were three in which similar signs and symptoms were described in association with pituitary tumors, which the authors considered to be incidental findings (3–5).