Harvey Cushing and Philip Hench: pituitary basophilism meets cortisone excess.

Arq Bras Endocrinol Metab 2007;51/8 Celebration of the 75th Anniversary of Cushing’s Syndrome IT IS OPPORTUNE THAT THIS ESPECIAL issue of the Brazilian Journal of Endocrinology and Metabolism comes out just in time to celebrate the 75th anniversary of the original description of the disease that turned out to be known as Cushing’s syndrome. Harvey Williams Cushing (April 8, 1869 — October 7, 1939) was a renowned neurosurgeon at the inception of endocrinology, and is distinguished today as the “father of modern neurosurgery”. A graduate of Yale College, Cushing spent most of his academic and professional life at Johns Hopkins and at Harvard Medical Schools, where his innovative and skilful approach to neurosurgery, introducing rigid homeostasis, asepsis, electrocoagulation, and other technical procedures, reduced mortality rates from brain surgery from 50 to 10% (1). Cushing was puzzled by a 23-year-old patient that had central obesity with contrasting skinny arms and legs, presence of bruises and large purplish striae spread upon a very thin, fragile, and almost translucent skin, a round and plethoric face resembling a “full moon”, prominent accumulation of dorsal fat, described as “buffalo hump”, in addition to hirsutism, amenorrhea, hypertension, and hyperglycemia. Although the hypothalamic–pituitary–adrenal axis and its interconnections were barely known at that time, Cushing described this astonishing condition as “pituitary basophilism”. Little was known about adrenal biosynthesis and corticosteroid production by the “supra renal capsules”. Cortisol excess, either by primary adrenal production or secondary to ACTH excess, and its resulting clinical manifestations are the quintessence of Cushing’s syndrome as we know it today. By 1912, however, little did Cushing know about these mechanisms when he published his initial monograph: “The pituitary body and its disorders” (2), in which he described the case of Minnie G., his first patient with typical stigmata of hypercortisolism. However, it was not until 20 years later that Cushing gathered another eleven patients with similar clinical characteristics who were reported in 1932 in a yet another seminal work: “Pituitary basophilism” (3). The florid clinical manifestations were ascertained to some sort of pituitary abnormality called “basophilism”, even though only three of the 12 reported patients were identified with a pituitary tumor. Indeed, in his landmark report, Cushing unintentionally described what appears to be the first cases of a “polyglandular syndrome”, since at autopsy several cases also presented hyperplasia of the adrenal glands in association with pituitary adenomas (3). Most interestingly, another patient from his series, with identical manifestations, had an adrenal adenoma found at autopsy, but no physiological relationship had been established. Only a few years later adrenal tumors were shown to cause the syndrome in some cases (4). editorial Harvey Cushing and Philip Hench: Pituitary Basophilism Meets Cortisone Excess