{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:06:47Z","timestamp":1770437207284,"version":"3.49.0"},"reference-count":43,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p>Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)\u2013secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.<\/jats:p>","DOI":"10.3171\/2011.8.jns102005","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T17:13:37Z","timestamp":1317402817000},"page":"261-268","source":"Crossref","is-referenced-by-count":24,"title":["The history of pituitary surgery for Cushing disease"],"prefix":"10.3171","volume":"116","author":[{"given":"Gautam U.","family":"Mehta","sequence":"first","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; and"},{"name":"Department of Neurosurgery, University of Virginia Health System, University of Virginia, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell R.","family":"Lonser","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward H.","family":"Oldfield","sequence":"additional","affiliation":[{"name":"Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; and"},{"name":"Department of Neurosurgery, University of Virginia Health System, University of Virginia, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-jns102005","series-title":"Harvey Lectures","first-page":"123","article-title":"Cushing's syndrome: its pathological physiology, its relationship to the adreno-genital syndrome, and its connection with the problem of the reaction of the body to injurious agents","volume":"38","author":"Albright","year":"1943"},{"key":"b2-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"1101","article-title":"Successful treatment of a case of Cushing's syndrome by electrocoagulation of the hypophysis","volume":"13","author":"Arner","year":"1953"},{"key":"b3-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"859","article-title":"Effects of x-irradiation on the hypothalamus: a possible explanation for the therapeutic benefits following x-irradiation of the hypophysial region for pituitary dysfunction","volume":"14","author":"Arnold","year":"1954"},{"key":"b4-jns102005","series-title":"Acta Med Scand","first-page":"411","article-title":"The so-called Cushing's Syndrome, its history, terminology and differential diagnosis","volume":"137","author":"Bauer","year":"1950"},{"key":"b5-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"1251","article-title":"Cure of Cushing's disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica","volume":"45","author":"Bigos","year":"1977"},{"key":"b6-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"348","article-title":"Cushing's disease: management by transsphenoidal pituitary microsurgery","volume":"50","author":"Bigos","year":"1980"},{"key":"b7-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"8","article-title":"Roentgen therapy in Cushing's syndrome without adrenocortical tumor","volume":"17","author":"Boucot","year":"1957"},{"key":"b8-jns102005","series-title":"Am J Surg Pathol","first-page":"100","article-title":"The search for Harvey Cushing's patient, Minnie G., and the cause of her hypercortisolism","volume":"19","author":"Carney","year":"1995"},{"key":"b9-jns102005","series-title":"Lancet","first-page":"347","article-title":"The adrenotropic hormone of the anterior pituitary lobe","volume":"222","author":"Collip","year":"1933"},{"key":"b10-jns102005","series-title":"Am J Pathol","first-page":"205","article-title":"Subclinical adenoma of the pituitary gland","volume":"12","author":"Costello","year":"1936"},{"key":"b11-jns102005","series-title":"Proc R Soc Med","first-page":"153","article-title":"Basophilism treated unsuccessfully with massive doses of oestrogens and deep x-ray therapy, but cured by radon seeds inserted into the sella turcica","volume":"40","author":"Crooke","year":"1947"},{"key":"b12-jns102005","series-title":"Bull Johns Hopkins Hosp","first-page":"137","article-title":"The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism)","volume":"50","author":"Cushing","year":"1932"},{"key":"b13-jns102005","series-title":"JAMA","first-page":"281","article-title":"Further notes on pituitary basophilism","volume":"99","author":"Cushing","year":"1932"},{"key":"b14-jns102005","series-title":"Brain","first-page":"282","article-title":"The meningiomas (dural endotheliomas): their source, and favoured seats of origin","volume":"45","author":"Cushing","year":"1922"},{"key":"b15-jns102005","series-title":"The Pituitary Body and Its Disorders: Clinical States Produced by Disorders of the Hypophysis Cerebri","author":"Cushing","year":"1912"},{"key":"b16-jns102005","series-title":"Proc R Soc Med","first-page":"853","article-title":"Radiotherapy in the treatment of pituitary basophilism and eosinophilism","volume":"42","author":"Ellis","year":"1949"},{"key":"b17-jns102005","series-title":"Beitr Pathol Anat","first-page":"1","article-title":"\u00dcber die Schwangerschaftsver\u00e4nderung der Hypophyse","volume":"46","author":"Erdheim","year":"1909"},{"key":"b18-jns102005","series-title":"Neurochirurgia (Stuttg)","first-page":"133","article-title":"[Excision of pituitary adenomas by transsphenoidal route.]","volume":"1","author":"Guiot","year":"1959"},{"key":"b19-jns102005","series-title":"Transact Clin Soc Lond","first-page":"175","article-title":"Precocious obesity, premature sexual and physical development, and hirsuties in relation to hypernephroma and other morbid conditions","volume":"40","author":"Guthrie","year":"1907"},{"key":"b20-jns102005","series-title":"BMJ","first-page":"1150","article-title":"Preliminary note on experimental investigations on the pituitary body","volume":"2","author":"Handelsmann","year":"1911"},{"key":"b21-jns102005","series-title":"Clin Neurosurg","first-page":"185","article-title":"Transphenoidal microsurgery of the normal and pathological pituitary","volume":"16","author":"Hardy","year":"1969"},{"key":"b22-jns102005","series-title":"J Neurosurg","first-page":"582","article-title":"Transsphenoidal hypophysectomy","volume":"34","author":"Hardy","year":"1971"},{"key":"b23-jns102005","series-title":"Diagnosis and Treatment of Pituitary Tumors. International Congress Series No. 303","first-page":"180","article-title":"Transsphenoidal surgery of hypersecreting pituitary tumors","author":"Hardy","year":"1973"},{"key":"b24-jns102005","series-title":"Klin Wochenschr","first-page":"1348","article-title":"\u00dcber Hormonuntersuchungen bei Morbus Cushing","volume":"14","author":"Jores","year":"1945"},{"key":"b25-jns102005","series-title":"Ann N Y Acad Sci","first-page":"540","article-title":"The chemistry and partial synthesis of adrenal steroids","volume":"50","author":"Kendall","year":"1949"},{"key":"b26-jns102005","series-title":"Ann N Y Acad Sci","first-page":"657","article-title":"Cushing's disease; a primary disorder of the adrenal cortices?","volume":"50","author":"Kepler","year":"1949"},{"key":"b27-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"1528","article-title":"Pseudotumor cerebri after surgical remission of Cushing's disease","volume":"95","author":"Kiehna","year":"2010"},{"key":"b28-jns102005","series-title":"Die Deutsche Klinik am Eingange des zwanzigsten Jahrhunderts","article-title":"Hirnchurgie","volume":"VIII","author":"Krause","year":"1905"},{"key":"b29-jns102005","series-title":"Am J Med","first-page":"638","article-title":"Pathogenesis of glucocorticoid disorders","volume":"53","author":"Liddle","year":"1972"},{"key":"b30-jns102005","series-title":"Adv Intern Med","first-page":"155","article-title":"The evolution of Cushing's syndrome as a clinical entity","volume":"15","author":"Liddle","year":"1969"},{"key":"b31-jns102005","series-title":"Pituitary","first-page":"97","article-title":"Cushing's syndrome: historical aspects","volume":"3","author":"Lindholm","year":"2000"},{"key":"b32-jns102005","series-title":"J Nerv Ment Dis","first-page":"727","article-title":"Hypophysectomy in Cushing's disease","volume":"99","author":"Lisser","year":"1944"},{"key":"b33-jns102005","series-title":"Virchows Arch Path Anat","first-page":"44","article-title":"Die Entwicklung der Hypophysisadenome","volume":"188","author":"L\u00f6wenstein","year":"1907"},{"key":"b34-jns102005","series-title":"Proc R Soc Med","first-page":"845","article-title":"Radon implantation for acromegaly and Cushing's syndrome","volume":"42","author":"Northfield","year":"1949"},{"key":"b35-jns102005","series-title":"Lancet","first-page":"1265","article-title":"Surgical treatment of pituitary basophilism","volume":"231","author":"Pattison","year":"1938"},{"key":"b36-jns102005","series-title":"Rev Neurol","first-page":"313","article-title":"Tumeurs du lobe ant\u00e9rieur de l'hypophyse. Essai de classification histologique","volume":"22","author":"Roussy","year":"1911"},{"key":"b37-jns102005","series-title":"J Clin Endocrinol Metab","first-page":"1523","article-title":"Pituitary tumors in patients with Cushing's syndrome","volume":"19","author":"Salassa","year":"1959"},{"key":"b38-jns102005","series-title":"Mayo Clin Proc","first-page":"24","article-title":"Transsphenoidal removal of pituitary microadenoma in Cushing's disease","volume":"53","author":"Salassa","year":"1978"},{"key":"b39-jns102005","series-title":"Wien Klin Wochenschr","first-page":"621","article-title":"Erfolgreiche Operation eines Hypophysentumors auf nasalem Wege","volume":"20","author":"Schloffer","year":"1907"},{"key":"b40-jns102005","series-title":"J Biol Chem","first-page":"923","article-title":"The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma","volume":"210","author":"Silber","year":"1954"},{"key":"b41-jns102005","series-title":"Br J Surg","first-page":"539","article-title":"Adenomata of the pituitary, with special reference to pituitary basophilism of Cushing","volume":"22","author":"Susman","year":"1935"},{"key":"b42-jns102005","series-title":"N Engl J Med","first-page":"753","article-title":"Cushing's disease. Selective trans-sphenoidal resection of pituitary microadenomas","volume":"298","author":"Tyrrell","year":"1978"},{"key":"b43-jns102005","series-title":"Am J Anat","first-page":"421","article-title":"The permeability of the hypophysis and hypothalamus to vital dyes, with a study of the hypophyseal vascular supply","volume":"58","author":"Wislocki","year":"1936"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/116\/2\/article-p261.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/116\/2\/article-p261.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/116\/2\/article-p261.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:45:32Z","timestamp":1679877932000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/116\/2\/article-p261.xml"}},"subtitle":["Historical vignette"],"short-title":[],"issued":{"date-parts":[[2012,2]]},"references-count":43,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3171\/2011.8.jns102005","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2]]}}}