Harvey Cushing's Influence on Norman Dott's Work on Acromegaly: Pituitary Research, Treatment Modalities, and Research Dissemination c.1900-c.1960.

OBJECTIVE: To review Dr. Harvey Cushing's influence on Mr. Norman Dott's work on acromegaly and other subjects surrounding the pituitary gland such as pituitary research, treatment modalities, and research dissemination. Dott was the first Professor of Neurosurgery in Scotland during 1947 and was considered a pioneer of the understanding and treatment modalities for pituitary disorders such as acromegaly. During 1923, he published an article regarding pituitary physiology that won him the award for the Rockefeller Fellowship Trust, to travel to Boston Massachusetts, giving him the opportunity to train under Cushing's supervision for the years of 1923-1924. However, similarities can be seen between Dott's physiology project that was completed before he ever met Cushing, as well as his treatment suggestions for acromegaly, after he had finished his training under Cushing's supervision. METHODS: This was a historical perspective based on literature review. We reviewed Norman Dott's archives held by University of Edinburgh Library or online sources and we compared these with the work Cushing had previously performed in a chronological fashion. Cushing's work on the pituitary gland and acromegaly can be largely found online, in biographical books, and in other secondary sources. The search included words such as "transsphenoidal surgery," "x-ray," "Harvey Cushing," "Norman Dott," "Acromegaly," "Annual Meetings," and "Pituitary physiology." We excluded any primary sources that were not published between 1900 and 1960 regarding either pituitary physiology or the treatments for acromegaly. CONCLUSIONS: Sir Norman Dott was the first Professor of Neurosurgery in Scotland during 1947 and is well known for his pioneering work on intracranial aneurysms. Although less well known for his contribution to pituitary pathologies, we would like to share his contribution in this regard and correlate it with Cushing's influence.

Hereditary Gigantism-the biblical giant Goliath and his brothers.

The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

A history of pituitary pathology.

The history of pituitary pathology is a long one that dates back to biblical times, but the last 25 years have represented an era of "coming of age." The role of the pituitary in health and disease was the subject of many studies over the last century. With the development of electron microscopy, immunoassays, and immunohistochemistry, the functional alterations associated with pituitary disease have been clarified. The additional information provided by molecular genetic studies has allowed progress in understanding the pathogenesis of pituitary disorders. Nevertheless, many questions remain to be answered. For example, pathologists cannot morphologically distinguish locally aggressive adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell carcinoma, the most common carcinoma of skin, usually causes less morbidity than pituitary adenomas, which occur in almost 20 % of the general population, can cause significant illness and even death, and yet are still classified as benign. The opportunity to increase awareness of the impact of these common lesions on quality of life is the current challenge for physicians and patients. We anticipate that ongoing multidisciplinary approaches to pituitary disease research will offer new insights into diseases arising from this fascinating organ.

Sellar door: Harvey Cushing's entry into the pituitary gland, the unabridged Johns Hopkins experience 1896-1912.

OBJECTIVE: To review the original surgical records from the Johns Hopkins Hospital, and analyze the records of patients Cushing treated for pituitary disorders from 1896 to 1912. METHODS: Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, we reviewed the original surgical files from the Johns Hopkins Hospital. Patients presenting with pituitary-related symptoms, who underwent surgical treatment directed at the pituitary gland, were selected for further review. RESULTS: Thirty-seven patients who underwent surgical intervention for pituitary disorders were found. Of these patients, 12 were mentioned only briefly in Cushing's 1912 monograph, whereas 6 were not described at all. The remaining 19 were documented by Cushing in his 1912 monograph. Cushing used three main surgical approaches to the pituitary: transsphenoidal, transcranial, and the subfrontal "omega incision." There were 6 inpatient deaths. The mean time to last follow-up was 41.0 months. At follow-up, headache was the most common unresolved symptom. CONCLUSION: This review highlights Cushing's accomplishments in the surgical treatment of suspected pituitary pathology during his early career as a young attending at Johns Hopkins Hospital. It reveals new information about patients whom Cushing did not include in his publications detailing his surgical experience at the Johns Hopkins Hospital.

The pituitary gland: a brief history.

The functions of the pituitary gland as an important constituent of the endocrine system were not understood until the latter part of the nineteenth century and the first half of the 20th century. At one time, the pituitary was deemed to be the "leader of the endocrine orchestra," but more recent studies have shown that its secretions are influenced by external stimuli and that it is largely under the control of the hypothalamus.

Cushing's contributions to neuroscience, part 2: Cushing and several dwarfs.

Harvey Cushing revolutionized modern neurosurgery and pioneered the field of neuroendocrinology. This second of a two-part series on Harvey Cushing's contributions to neuroscience discusses his pivotal discoveries of the function and clinical disorders of the anterior pituitary. A review of his 20-year obsession with the pituitary reveals Cushing's ingenuity, keen sense of observation, and persistent stubborness. His enthusiasm to test his ideas, however, led to risky experimentation. Despite his foibles, his work opened up new frontiers of research for a number of investigators, whose efforts resulted in the identification of specific pituitary hormones, the hypothalamic regulation of the pituitary, and the practical applications of endocrinology.

[History of pituitary surgery in humans and animals: from experiments with dogs to treatment of patients]. / Geschiedenis van de hypofysechirurgie bij mens en dier: van experimenten bij honden naar behandeling van patiënten.

At the end of the 19th century and the start of the 20th century experimental hypophysectomy was carried out on cats and dogs, by means of the lateral temporal approach, to investigate the physiological role of the pituitary gland because there was a debate as to whether the pituitary gland was essential for life. At the same time pioneering neurosurgeons such as Harvey Cushing used animal experiments to explore the different approaches to the neurocranium and the pituitary, thereby taking the first steps towards neurosurgery in humans. Eventually the transsphenoidal route was chosen for such an operation. Veterinary medicine has benefited from these developments in the medical field. For the past few decades, hypophysectomy has been used for the treatment of pituitary adenomas in dogs and cats that are kept as pets.

Triumph and disaster. Early experiences in pituitary surgery.

The year--1932. The place--St Vincent's Hospital, Sydney. I was a young surgeon with a sort of evangel for surgical teaching, and met regularly with a group of students in the outpatient department.

Harvey Cushing as clinical investigator and laboratory worker.

This assay is not a history of the pituitary gland, or an abbreviated life of Cushing, or a comprehensive review of hypophysial endocrinology. What is attempted is a short evaluation of this medical "classic" as a contribution to the history of ideas about the function of the anterior pituitary and about clinical disorders of the gland.