Wednesday, April 28, 2010

Cushing's Syndrome Associated With a Thrombophilic State, Changes in the Fibrinolytic System: Presented at ECE

By Karen Dente

PRAGUE, Czech Republic -- April 27, 2010 -- Patients with Cushing's syndrome have an increased tendency for coagulation and thrombosis, especially since high concentrations of glucocorticoids result in reduced fibrinolytic capacity and increases in the plasma clotting factors, in particular of von Willebrand factor (vWf).

A longitudinal study following 40 patients was presented here during a poster presentation on April 26 at the 12th European Congress of Endocrinology (ECE).

"The aim of our study was to evaluate the haemostatic and fibrinolytic markers in patients with active Cushing's syndrome during the activity and after the remission or the persistency of the disease," said Valentina Raffaelli, MD, Department of Endocrinology, University of Pisa, Pisa, Italy.

Of the 40 patients, all with active Cushing's syndrome, 31 were women and 9 were men. A total of 36 were affected by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas and 4 by adrenal adenomas. Haemostatic and fibrinolytic markers were evaluated in all patients during the activity of the disease and after surgery.

None of the patients received any kind of medication that affected coagulation tests.

A year or two after surgery all patients were re-evaluated. At this point 27 patients presented with remission (group 1), and 13 patients demonstrated persistent hypercortisolism (group 2).

Compared with patients in the active group, patients in the remission group had different levels of von Willebrand factor (P < .0001), plasminogen activator inhibitor (PAI-1; P = .003), antithrombin III (P = .0002), and plasmin-antiplasmin complex (P = .006).

In terms of other markers including fibrinogen, prothrombin fragment 1 and 2, factor V, factor VII, factor IX, factor XII, activated partial thromboplastin time, thrombin-antithrombin complex, plasminogen, and D-dimer, no differences were observed between the active and remission patients.

"The study confirms that Cushing's syndrome is associated with a thrombophilic state and changes in the fibrinolytic system," said Dr. Raffaelli. Recent studies provide further evidence that genetic polymorphisms in the vWf and PAI-1 can influence the corticosteroid-mediated transcriptional regulation of these factors.

Further studies are required to better delineate the exact changes in the coagulation cascade in hypercortisolism, says Dr. Raffaelli.

[Presentation title: Evaluation of Haemostatic and Fibrinolytic Marker in Patients With Cushing's Syndrome: A Longitudinal Study. Abstract 5]


Friday, April 16, 2010

Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing's Disease

Jitske Tiemensma*, Nieke E. Kokshoorn, Nienke R. Biermasz, Bart-Jan S. A. Keijser, Moniek J. E. Wassenaar, Huub A. M. Middelkoop, Alberto M. Pereira,  and Johannes A. Romijn

Departments of Endocrinology and Metabolism (J.T., N.E.K., N.R.B., B.-J.S.A.K., M.J.E.W., A.M.P., J.A.R.) and Neurology (H.A.M.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

* To whom correspondence should be addressed. E-mail:

Context and Objective: Active Cushing's disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing's disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing's disease.

Design: Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning.

Patients and Control Subjects: We included 74 patients cured of Cushing's disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education.

Results: Compared with NFMA patients, patients cured from Cushing's disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing's disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing's disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing's disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients.

Conclusions: Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing's disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.



Monday, April 12, 2010

Adrenal Insufficiency

Clinical Background

Adrenal insufficiency is defined as hypofunction of the adrenal gland with decreased or absent cortisol secretion.


  • Incidence – estimated at 5/100,000
  • Sex – M:F, equal


  • Primary or secondary insufficiency


  • Causes of primary adrenal insufficiency
    • Autoimmune  (Addison disease)
      • Frequent association with other endocrine diseases
        • Autoimmune polyendocrine syndromes
          • Epidemiology
            • Incidence – 1-2/100,000
            • Age – usually in 30s
            • Sex – M<F, 1:3
          • Most frequent endocrine abnormality is adrenal insufficiency
          • Type 1
            • Addison disease
            • Chronic mucocutaneous candidiasis
            • Hypoparathyroidism
          • Type 2
            • Diabetes mellitus type 1 (DM1)
            • Addison disease with hypothyroidism – Schmidt syndrome
        • Both types 1 and 2 may also include:
          • DM1
          • Other autoimmune disorders – vitiligo, chronic atrophic gastritis, alopecia
      • Autoantibodies to 21-hydroxylase are frequently present
    • Anatomic destruction of the gland
      • Surgical removal
      • Bilateral hemorrhage into the gland
        • Associated with anticoagulant therapy
      • Invasion of the gland
        • Metastatic cancer is extremely rare
    • Infection
      • Bacterial
        • Tuberculosis
        • Meningococcus (Waterhouse-Friderichsen) – rare
        • Pseudomonas – rare
      • Fungal – histoplasmosis, coccidioidomycosis
      • Viral – cytomegalovirus (CMV), AIDS
    • Congenital adrenal hyperplasia (CAH)
  • Causes of secondary adrenal insufficiency
    • Hypopituitarism
      • Postpartum hemorrhage – Sheehan syndrome
      • Pituitary radiation
      • Pituitary surgery
      • Acute interruption of prolonged corticosteroids
      • Pituitary infiltrative disease – tuberculosis, sarcoidosis, Wegener granulomatosis
    • Exogenous glucocorticoid administration
    • Lymphocytic hypophysitis – may be part of autoimmune polyendocrine syndrome


  • Primary – glucocorticoid and mineralocorticoid deficiency
  • Secondary – only glucocorticoid deficiency

Clinical Presentation

  • Insidious onset of fatigue, weakness, anorexia, nausea and emesis
  • Cutaneous hyperpigmentation – diffuse tan, brown or bronzing
    • Does not occur in secondary insufficiency
  • Orthostatic hypotension
  • Diarrhea, abdominal pain
  • Acute presentation may occur in patients with mild adrenal insufficiency who are stressed (eg, critical illness, surgery)
    • Mainly attributable to mineralocorticoid deficiency
    • Hypotension which is unresponsive to fluids


  • Primary – glucocorticoids and mineralocorticoids in primary
  • Secondary – glucocorticoids only
  • Increase glucocorticoid dosing during acute illness


  • Indications for testing – presence of disease process associated with adrenal insufficiency and other symptoms consistent with adrenal insufficiency
  • Laboratory testing
    • Initial testing
      • First, measure early morning serum cortisol
        • Cortisol ≥5 µg/dL makes primary adrenal insufficiency less likely; however, if serious consideration is given to this diagnosis, perform stimulation testing
      • Follow with adrenocorticotropic hormone (ACTH) testing
        • If ACTH >300 pg/dL – adrenal failure likely
        • If ACTH <10 pg/dL – pituitary failure likely
        • If ACTH between 10 pg/dL and 300 pg/dL – administer ACHT (cosyntropin) stimulation test
    • Stimulation
      • ACTH stimulation test – cortisol response to cosyntropin (250 µg followed by serial cortisol measures at 30 and 60 minutes)
        • Cortisol <5 µg/dL – adrenal failure
        • Cortisol >20 µg/dL – normal
        • Cortisol ≤20 µg/dL but ≥5 µg/dL – evaluate for pituitary failure
      • Pituitary failure stimulation testing
        • Insulin tolerance testing (ITT)
        • Metyrapone overnight testing
        • CT/MRI anatomic location based on cortisol ratios (see Adrenal Insufficiency Testing Algorithm)
  • Imaging studies
    • MRI/CT based on stimulation testing
    • If stimulation testing or absolute cortisol suggests adrenal failure – MRI/CT of adrenal glands
    • If stimulation testing suggests pituitary failure – MRI/CT of pituitary

Differential Diagnosis

  • Bronchogenic carcinoma
  • Hemochromatosis
  • Peutz-Jeghers syndrome
  • Tuberculosis
  • Congenital adrenal hyperplasia
  • Malnutrition


More at

Saturday, April 10, 2010

The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline - Commentary from a European Perspective.

Guignat L, Bertherat J.

L Guignat, France.


Cushing's syndrome is considered a rare disease and its diagnosis can be challenging. Establishment of evidence based recommendations is difficult. In 2008, several national and international consensus recommendations for the diagnosis or management of Cushing's syndrome have been reported. The Endocrine Society, with participation of the European Society of Endocrinology, has developed a task force to update recommendations for the diagnosis of Cushing's syndrome. The main aspects of these recommendations are presented in this article and discussed in the context of current research efforts in Europe focusing on the improvement of diagnosis and management of rare diseases including adrenal disorders such as Cushing's.

PMID: 20375177 [PubMed - as supplied by publisher]


Friday, April 9, 2010

World Cushing’s Awareness Day

Chesterfield, MO–This afternoon at the Samuel C Sachs branch of St Louis County Library, Mayor John Nations of Chesterfield proclaimed today ‘World Cushings [sic] Syndrome Awareness Day’.

Mr Nations presented this proclamation to Ms Susan K Findley, a survivor of the syndrome. She said ‘It was an honor to be recognized by the mayor today. I greatly appreciate him taking time to attend our Cushing’s Awareness event and for issuing and presenting me with the proclamation. He has helped to stoke the fire for my endeavor of speading [sic] the word about Cushing’s. I will continue my fight against this brutal condition that could have ended my life and has ended many lives of people around the world, including a couple friends of mine. Lingering symptoms continue to affect me in most of my daily activities, though I am very fortunate to have support of fellow ‘Cushies’ in groups like ‘Cushies on Facebook’. My hope is to spread knowledge and awareness about Cushing’s Syndrome, starting online and in my local community, and not stop until there is global awareness so that no more lives are claimed by this horrible condition that doesn’t care who it ambushes.’

Cushing’s Syndrome is named after the doctor who discovered it, Dr Harvey Williams Cushing, nearly 80 years ago. It is an endocrine disorder caused by high levels of cortisol in the blood. It also has many causes and can manifest over a very short or long time. The symptoms are often misdiagnosed as a combination of other ailments.

Susan Kate Findley is still fighting Cushing’s and intends to continue her advocacy on a global level. She invites everyone to visit the ‘Cushies on Facebook’ group at .

Cushings Proclamation 2010


Blood Pressure That Won't Budge

DEAR DR. DONOHUE: I've had severe high blood pressure for many years. I have tried all the medicines you can think of. I am 62 and have had one ministroke. I'm not looking for another. I used to weigh 235 pounds. I lost 100 pounds. I watch my salt. I have tried everything. My family has a history of high blood pressure. Can you recommend anything? -- F.

ANSWER: Blood pressure that doesn't drop by making life changes (weight loss and diet) or by taking three or four blood pressure medicines is called resistant high blood pressure (hypertension). Your weight loss is admirable. It should have reduced your pressure.

Watching your salt intake is also important. That entails more than not using the salt shaker. It requires you to carefully look for the salt content (listed as sodium or sodium chloride) of all your foods. Commercial soups, frozen dinners, many canned goods and luncheon meats often have a high salt content. Your diet should be one of fruits, vegetables, whole grains (unrefined wheat, barley, rye and oats) and one where meat and fats are eaten sparingly.

Increase foods with lots of potassium in them: tomatoes, potatoes, prunes, lima beans, kidney beans, navy beans, bananas, oranges and orange juice, spinach, peaches, cantaloupe and broccoli. Potassium lowers blood pressure.

Exercise for 30 minutes every day. Get your doctor's approval first, and start out modestly. Brisk walking is fine.

For resistant high blood pressure, your doctor has to look for the less-common causes of it. Sleep apnea (loud snoring with pauses when there is no breathing), adrenal gland tumors, Cushing's syndrome, narrowed kidney arteries and rare tumors such as pheochromocytoma are cases in point.

Go over your medicines. Some medicines raise pressure. Nonsteroidal anti-inflammatory drugs are an example -- Aleve, Advil, Motrin, aspirin and other NSAIDs. Don't drink more than two alcohol drinks a day.

More than 30 blood pressure medicines are on the market. I bet you haven't tried all 30 or combinations of them. Some brands come with two medicines in one pill, easing the burden of pill-taking. A new medicine, one completely different from all other medicines, is now available. It is Tekturna. Something must be done for your pressure.

The booklet on high blood pressure gives the story of this very common malady. To receive a copy, write: Dr. Donohue -- No. 104W, Box 536475, Orlando, FL 32853-6475. Enclose a check or money order (no cash) for $4.75 U.S./$6 Canada with the recipient's printed name and address. Allow four weeks for delivery.



Thursday, April 8, 2010

Pseudotumor Cerebri after Surgical Remission of Cushing’s Disease

Erin N. Kiehna, Meg Keil, Maya Lodish, Constantine Stratakis and Edward H. Oldfield

Department of Neurosurgery (E.N.K., E.H.O.), University of Virginia, Charlottesville, Virginia 22908-0212; and Section on Endocrinology and Genetics (M.K., M.L., C.S.), Program in Developmental Endocrinology and Genetics, and Pediatric Endocrinology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Edward H. Oldfield, M.D., Department of Neurological Surgery, University of Virginia, P.O. Box 800212, Charlottesville, Virginia 22908-0212.

Context: Pseudotumor cerebri has only been described after successful surgery for Cushing’s disease (CD) in case reports. We sought to establish the incidence and timing of its occurrence, identify predisposing factors, characterize the clinical presentations and their severity, and examine the effects of treatment in patients who underwent surgery for CD.

Setting: This study was conducted at two tertiary care centers: The University of Virginia and the National Institutes of Health.

Patients: We conducted a retrospective review of 941 surgeries for CD (723 adults, 218 children) to identify patients who developed pseudotumor cerebri after surgery for CD and examine the associated clinical features.

Results: Seven children (four males, three females; 3%), but no adults, developed pseudotumor cerebri postoperatively. All underwent resection of an ACTH-secreting adenoma, and postoperative serum cortisol reached a nadir of less than 2 µg/dl. After surgery, all were placed on tapering hydrocortisone replacement therapy. Within 3–52 wk, all seven patients experienced symptoms of pseudotumor cerebri and had ophthalmological examination demonstrating papilledema. One patient had diplopia from a unilateral VIth nerve palsy. Six patients were still on steroid replacement at onset of symptoms. In three patients, a lumbar puncture demonstrated elevated opening pressure. Four patients were treated successfully with a lumbar puncture, steroids, and/or Diamox. Three patients did not receive treatment, and their symptoms resolved over several months. There was no correlation between the degree of hypercortisolism (24-h urinary free cortisol) before surgery and the likelihood of developing pseudotumor cerebri after surgery (P < 0.23).

Conclusions: This series demonstrates a 3% occurrence of pseudotumor cerebri in children after successful surgery for CD, but the absence of the syndrome in adults. Pseudotumor cerebri manifests itself within 1 yr of surgery, often while patients are still undergoing replacement steroid therapy. A patient exhibiting signs of intracranial hypertension after surgery for CD should undergo an evaluation for pseudotumor cerebri. Recognition of the symptoms and treatment should correct and/or prevent ophthalmological sequelae.



It’s Another Cushing Awareness Day in Honor of Dr Harvey Cushing’s Birthday.


From the archives: SPECIAL Cushing's Awareness Day Voice Chat! - April 08, 2008

Listen as Jayne Kerns and Robin Smith (staticnrg) hosted a Cushing's Awareness Day Special Chat

This chat had callers and some testimonials for the website and Mary O'Connor (MaryO).

Ideas were discussed for setting up non-profit status for this website.

Some past events:

For Immediate Release:

April 6, 2006


WASHINGTON, D.C. – U.S. Senator James M. Inhofe (R-Okla.) is proud to announce the designation of April 8, 2006 as “National Cushing’s Syndrome Awareness Day.” Inhofe’s resolution (S. Res. 423) creating the designation passed the Senate by unanimous consent. Inhofe introduced this resolution to broaden public awareness and show his continued support for those suffering from this disease.

“My desire is to see my Oklahoma constituents and all Americans receive the best possible health care,” Inhofe stated. “Cushing’s syndrome often goes undiagnosed or misdiagnosed, many times leading to death, because the initial symptoms are shared with a number of milder ailments. Since awareness of the syndrome is low, doctors do not always run the tests necessary for diagnosis, and patients do not know to ask for them. It is my hope that ‘National Cushing’s Syndrome Awareness Day’ will help Okies and everyone suffering with this disease to receive better health care.”

Cushing’s Syndrome is an endocrine or hormonal disorder. It is caused by over-exposure of the body’s tissue to high levels of hormone cortisol. An estimated 10 to 15 people per million suffer from this debilitating disease. Common symptoms include abnormal weight gain, skin changes, fatigue, diabetes, high blood pressure, and depression.

Over production of cortisol is commonly associated with the treatment of asthma, rheumatoid arthritis, and lupus. Additionally, delayed treatment of Cushing’s Syndrome significantly reduces treatment options, such as radiation therapy. Thus, it is imperative that both doctors and patients heighten their awareness of Cushing’s Syndrome.

April 8, 2006, the Cushing's Understanding, Support & Help Organization (CUSH) petitioned in the USA to have April 8 be declared as Cushing's Awareness Day. This date was chosen because it was Dr. Harvey Cushing's Birthday. More info here

The Cushing's Awareness Day Proclamation, from

Designating April 8, 2006, as `National Cushing's Syndrome Awareness Day'. (Agreed to by Senate)



2d Session

S. RES. 423

Designating April 8, 2006, as `National Cushing's Syndrome Awareness Day'.


April 4, 2006

Mr. INHOFE (for himself and Mr. COBURN) submitted the following resolution; which was considered and agreed to

RESOLUTION Designating April 8, 2006, as `National Cushing's Syndrome Awareness Day'.

Whereas Cushing's Syndrome annually affects an estimated 10 to 15 people per million, most of whom are currently between the ages of 20 and 50;

Whereas Cushing's Syndrome is an endocrine or hormonal disorder caused by prolonged exposure of the body's tissue to high levels of the hormone cortisol;

Whereas exposure to cortisol can occur by overproduction in the body or by taking glucocorticoid hormones, which are routinely prescribed for asthma, rheumatoid arthritis, lupus, or as an immunosuppressant following transplantation;

Whereas the syndrome may also result from pituitary adenomas, ectopic ACTH syndrome, adrenal tumors, and Familial Cushing's Syndrome; Whereas Cushing's Syndrome can cause abnormal weight gain, skin changes, and fatigue and ultimately lead to diabetes, high blood pressure, depression, osteoporosis, and death;

Whereas Cushing's Syndrome is diagnosed through a series of tests, often requiring x-ray examinations of adrenal or pituitary glands to locate tumors;

Whereas many people who suffer from Cushing's Syndrome are misdiagnosed or go undiagnosed for years because many of the symptoms are mirrored in milder diseases, thereby delaying important treatment options; Whereas treatments for Cushing's Syndrome include surgery, radiation, chemotherapy, cortisol-inhibiting drugs, and reducing the dosage of glucocorticoid hormones;

Whereas Cushing's Syndrome was discovered by Dr. Harvey Williams Cushing, who was born on April 8, 1869;

Whereas the Dr. Harvey Cushing stamp was part of the United States Postal Service's `Great American' series, initiated in 1980 to recognize individuals for making significant contributions to the heritage and culture of the United States;

Whereas President Ronald Reagan spoke on April 8, 1987, in the Rose Garden at a White House ceremony to unveil the commemorative stamp honoring Dr. Harvey Cushing;

Whereas following the ceremony, President Reagan hosted a reception in the State Dining Room for Mrs. John Hay Whitney, Dr. Cushing's daughter, and representatives of the American Association of Neurological Surgeons; and

Whereas the Senate is an institution that can raise awareness in the general public and the medical community of Cushing's Syndrome:

Now, therefore, be it Resolved, That the Senate--

(1) designates April 8, 2006, as `National Cushing's Syndrome Awareness Day';

(2) recognizes that all Americans should become more informed and aware of Cushing's Syndrome;

(3) calls upon the people of the United States to observe the date with appropriate ceremonies and activities; and

(4) directs the Secretary of the Senate to transmit a copy of this resolution to the Cushing's Understanding, Support & Help Organization

AutumnOMA April 8, 2006, National Cushings Awareness Day Holds Special Meaning for Local Woman


Dr. Cushing was born in Cleveland Ohio. The fourth generation in his family to become a physician, he showed great promise at Harvard Medical School and in his residency at Johns Hopkins Hospital (1896 to 1900), where he learned cerebral surgery under William S. Halsted

After studying a year in Europe, he introduced the blood pressure sphygmomanometer to the U.S.A. He began a surgical practice in Baltimore while teaching at Johns Hopkins Hospital (1901 to 1911), and gained a national reputation for operations such as the removal of brain tumors. From 1912 until 1932 he was a professor of surgery at Harvard Medical School and surgeon in chief at Peter Bent Brigham Hospital in Boston, with time off during World War I to perform surgery for the U.S. forces in France; out of this experience came his major paper on wartime brain injuries (1918). In addition to his pioneering work in performing and teaching brain surgery, he was the reigning expert on the pituitary gland since his 1912 publication on the subject; later he discovered the condition of the pituitary now known as "Cushing's disease".

On retiring from Harvard he spent his final years at Yale as professor of neurology and director of studies in the history of medicine; his bequest of his books on this latter field form the basis of Yale's medical history library.

America's most admired surgeon in his day, he was a man of many talents, even winning the Pulitzer Prize (1926) for his biography of the man who had greatly influenced his career, The Life of Sir William Osler.

From: Microsoft® Encarta® Online Encyclopedia 2000

Cushing, Harvey Williams

Cushing, Harvey Williams (1869-1939), innovative American brain surgeon. Born in Cleveland, Ohio, and educated at Harvard and Yale universities, Cushing was associate professor of surgery at Johns Hopkins University from 1902 until 1912.

He then served as professor of surgery at Harvard and surgeon in chief at the Peter Bent Brigham Hospital in Boston until 1933, when he became professor of neurology at Yale.

Cushing originated new techniques of brain surgery and made valuable contributions to the operative treatment of facial paralysis, cerebral tumors, and intracranial hemorrhage of newborn babies. He was also a pioneer in the use of X-rays and in the monitoring of blood pressure, and he drastically reduced the incidence of mortality in brain surgery. The extensive library that he bequeathed to Yale served as the nucleus for an outstanding collection of books on medical history. His writings include The Life of Sir William Osler (1925), which won the Pulitzer Prize, and 1915-1918 (1936).

"Cushing, Harvey Williams," Microsoft® Encarta® Online Encyclopedia 2000 © 1997-2000 Microsoft Corporation. All rights reserved.

Harvey Williams Cushing
Used with the permission of Ole Daniel Enersen, editor of, a biographical dictionary of medical eponyms on the Internet.

American neurosurgeon, born April 8, 1869, Cleveland, Ohio; died October 7, 1939, New Haven, Connecticut.

Associated eponyms:
Bailey-Cushing syndrome

A syndrome affecting both sexes with unsteadiness in balance, disturbed coordination of the body in space, walking very poor, good coordination when lying or with body well braced.

Cushing's clip
A small silver clip developed by Cushing in 1910.

Cushing's law
Increase in intracranial pressure causes compression of the cerebral blood vessels and cerebral ischemia.

Cushing's symphalangism
A syndrome of symphalangism with fusion of the midphalangeal joints, fusion of elbow and carpal and tarsal bones; absence of the normal articular folds.

Cushing's syndrome I
Glucocorticoid excess syndrome in which the hypersecretion of glucocorticoids is secondary to hypersecretion of adrenocorticotrophic hormone from the pituitary.

Cushing's syndrome II
A syndrome of multiple tumours of the spinal nerve roots and auditory nerves.

Cushing's syndrome III
A syndrome of bitemporal hemianopsia and associated primary optic atrophy

Cushing's triad
Signs of increased intracranial pressure.

Launois' syndrome
Syndrome that presents the characteristics of primary pituitary gigantism.

Neurath-Cushing syndrome
A syndrome combining the features of prepuberal adiposogenital dystrophy and gigantism.

Rokitansky-Cushing ulcer
Eponym used to indicate the gastrointestinal hemorrhagic complication arising after head injury or neurosurgery.

Slocumb's syndrome
A condition resulting from prolonged therapy of rheumatoid arthritis with corticoid steroids.



Harvey Williams Cushing was born in Cleveland, Ohio, the sixth son and the tenth child (seven lived to maturity) of Henry Kirke Cushing and Betsey Maria Williams Cushing. The Cushing family on the paternal side originated from Gravesend, England. Matthew Cushing, a deacon, emigrated to Boston in 1638. His great grandfather David (1768-1814) was country doctor, his grandfather Erastus (1802-1893) was also a general practitioner. His father, a stern puritanical doctor, combined a large practice with the professorship of midwifery, diseases of women, and medical jurisprudence at Cleveland Medical College and was also for many years a trustee of Case Western Reserve University. Reserved with his children, he left much responsibility for their upbringing to his wife, a gracious, highly intelligent woman quite capable of the task. He imposed strict discipline in his household and provided comfortably for physical needs - generously for education. Harvey’s mother came from a pioneer mid-western stock. One son entered the law, another geology; two became physicians. They attended the Presbyterian church, public schools in Cleveland, and eastern universities for their college and post-graduate training.

Student years
At the age of 18 Harvey Cushing went to Yale College, where four years nurtured an abiding loyalty to his alma mater, largely through the close friendships formed there and maintained and treasured all his life. After receiving his A.B. at Yale University in 1891, he followed his brother Edward into Harvard Medical School in 1891, becoming the fifth Cushing to enter medicine. Before enrolling at Harvard he was directed by his father to abstain from smoking, drinking, boating, baseball and other forms of intemperance. In 1894, the year before graduation, he visited London for the first time, meeting Jonathan Hutchinson (1828-1913) at his rooms and Thomas Barlow (1845-1945) at Great Ormond Street Hospital.

He received his MD cum laude in 1895 and became a surgical house officer at the Massachusetts General Hospital, Boston. Here he collaborated with Ernest Amory Codman (1869-1940), with whom he had devised the first anaesthetic chart, “The ether chart” in 1894, while still a student, prompted by the death of a patient during surgical procedure. This gave brief details of the patient and the operation and allowed both the anaesthetist and the surgeon to follow the condition of the patient throughout the operation by recording pulse, respiration and temperature. This innovation led to a considerable reduction in mortality rate from anaesthesia. Cushing and Codman now collaborated on the clinical use of X-rays, whose discovery had only been made in December the previous year by Röntgen. Even at this early stage in his career Cushing’s driving energy and his taskmaster attitude to his junior were becoming apparent.

Johns Hopkins
In 1896, at the age of 27, Cushing went on to become assistant resident at the newly founded Johns Hopkins Hospital where for four years he worked under William Stewart Halsted (1852-1922), the pre-eminent among American surgeons. Cushing was unimpressed both by the city of Baltimore and the hospital - "the hospital is a very sloppy place and the work of everyone most unsystematic, i.e. on the surgical side. Dr. Hallsted has only operated once this month and rarely appears. Hope things clear out or I can't stand it" - an extract from a letter he wrote home. He lived. However, next door to William Osler and a great friendship developed. The first professors at the newly established medical school were men of extraordinary high calibre, among them, besides Osler, was William Henry Welch (1850-1934) in the chair of pathology, and Howard Atwood Kelly (1858-1943) in charge of obstetrics.

Stimulated by these men, Cushing’s restless and inquiring mind and enormous capacity for work found full expression. Their interest in medical history spurred him in his collection of medical books; he was also encouraged by his father, who passed along volumes from his own library that also often carried the signatures of his grandfather and great-grandfather.

In 1898 Cushing had his first experience of military medicine and in surgery in dealing with soldiers, mostly suffering from typhoid fever, who were evacuated to Baltimore during the Spanish-American war in Cuba. From this resulted two of his early papers, on the treatment of typhoid perforation of the intestine.

Europe calls
After completing his time at Johns Hopkins, Cushing went to Europe and in Bern where he experimented under the direction of Theodor Kocher (1841-1917) on the relationship between systolic blood pressure and cranial pressure. In Bern he also worked with Hugo Kronecker (1839-1914) on the effects of raised intracranial pressure and noted the rise in blood pressure that accompanies it. From Bern he went to England, working with Victor Horsley in London, and during a month in Liverpool took part in Sir Charles Scott Sherrington's (1857-1952) experiments on the ape motor cortex. Perhaps the most important aspect of his visit was that William Osler, too, was spending the summer of 1900 in England, and it was during this period that Cushing began the firm friendship with Osler that was to continue until Osler’s death. Much of the success of this European visit was due to the numerous introductions that Osler could make for his young colleague. On this trip Cushing also visited surgical centres in France, Germany and Italy.

After spending the year 1900-1901 in Europe, Cushing in 1902 returned to Johns Hopkins, where he ran courses in surgical anatomy, and organized an experimental surgical laboratory in which junior students carried out operative surgical procedures on dogs. It was at this time that he began to move toward neurological surgery, particularly turning his attention during the next three years to patients with pituitary tumours. He was the first American to devote full time to the development of neurological surgery.

Family life
In 1902 Cushing married Katharine Stone Crowell, a Cleveland childhood friend. They had five children: William Harvey, Mary Benedict, Bestey, Henry Kirke and Barbara. The situation in his fathers household was repeated in his: he spent long hours at the hospital, then devoted evenings to writing. Yet many house officers and students remember the warm hospitality of a friendly family and Dr. and Mrs. Cushing as gracious hosts. Their elder son, William, a Yale student, was killed in an automobile accident in 1926, and Cushing's sorrow was deepened because he had only begun to know him.

Into neurosurgery
Cushing’s first experience of pituitary disease was in 1901, when he carried out a decompression of a girl aged 14 who had complained of headaches and visual failure. She was fat and sexually immature. At post mortem she was found to have a large pituitary cyst, In the same year, Alfred Fröhlich (1871-1953) reported a similar case from Vienna, a boy of 15 with headache, failure of vision, obesity and sexual immaturity. The patient was operated on by Anton von Eiselsberg (1860-1939), who drained a cystic tumour of the pituitary. Fröhlich syndrome passed eponymously into medical terminology. In this work it has been entered as Babinski-Fröhlich syndrome, named for Joseph Babinski (1857-1932) who described the condition in 1900, one year before Fröhlich.

Pity the pituitary
In March 1909 Cushing carried out his first operation for acromegaly. The patient was a 38-year old farmer referred by Charles Mayo. The approach to the pituitary was via a frontal flap opening the frontal sinuses. The patient made a remarkable recovery and lived until 1930. This was only the second successful case, the first having been operated by Herman Schloffer (1868-1937), then professor of surgery at Innsbruck, in 1907. Between 1909 and 1911, Cushing collected 46 patients with lesions involving the pituitary and most of these were subjected to surgery. The dangers and difficulties of these early operations are demonstrated by the fact that of three patients in this series with acromegaly who were operated upon, two died.

Cushing was associate Professor of Surgery at Johns Hopkins from 1903 to 1912. In 1910 he had accepted the appointment as Mosley Professor of Surgery and chairman of the department at Harvard Medical School, and Surgeon-in-Chief at the Peter Bent Brigham Hospital on the Harvard Medical School campus. He entered his new tenure when the new school opened in 1913, and remained until his retirement in 1932. The first patient to enter the surgical service – a woman with varicose veins of the legs – was admitted on January 27, 1913.

During World War I he was briefly in France in 1915 at the military hospital established at Neuilly outside Paris in the converted Lycée Pasteur, and again from 1917 to 1919 as chief of Base Hospital No. 5. During this time he had a brush with the military hierarchy. As a Colonel with a Harvard Unit serving with the British Expeditionary Forces, in a letter to his wife which was intercepted by French sensors, he made some harsh criticism of a British surgeon. The letter was handed over to the British government and he was threatened with a court martial. The matter was smoothed over eventually by him being transferred to an American command.

In 1936 he published From a Surgeons Journal, 1915-19 of his experiences in World War I which gives poignant descriptions of the wounded and a sad account of the death of Osler's only child Revere, at whose side he stayed until he died. He comments on the irony of a grandchild of the famous American patriot, Paul Revere, being buried wrapped in a Union Jack.

The roaring twenties
The 1920’s were a particularly fruitful period for Cushing. His clinical output was prodigious, and he trained a series of remarkable men, both from the USA and Europe, who themselves and, in turn, through their trainees spread the Cushing technique throughout the world. Among the most distinguished of those from the USA was Walter Edward Dandy (1886-1946), who introduced ventriculography and the radical excision of acoustic tumours.

Cushing's perhaps most important work in the 1920’s was in the problem of haemorrhage. One of the major technical problems that Cushing had to overcome in the development of surgery of the central nervous system was haemorrhage. The scalp itself is particularly vascular. In 1910 he developed a small silver clip (Cushing’s clip). Suction was introduced to deal with bleeding in deeply placed recesses of the skull. Most important, however, was his work on the application of electrical coagulation to neurosurgery. A large part of this was done with the physicist Dr. William Bovie. In 1926 he used the high-frequency current to remove a vascular myeloma invading the scalp. A previous attempt by Cushing to excise the tumour had failed because of haemorrhage. On this occasion, Cushing’s operation notes read,

”With Dr Bovies help I proceeded to take off most satisfactorily the remaining portion of the tumour with practically none of the bleeding which was occasioned in the preceding operation. The loop acted perfectly and blood stilling was almost complete but whether we would venture to use anything of this kind in the brain tissue itself I am at a loss to know because almost certainly it would cause convulsion.”

As he gradually solved the problems of brain surgery, patients and young physicians came to his clinic from all over the world. The results of his labours are recorded in 330 books and papers. In 1932, at the retirement age of 63, Cushing retired as Mosley professor, after occupying the chair for 20 years. He was replaced by Elliott Carr Cutler (1888-1947), who had been one of the early members of Cushing's house staff at the Bingham. In 1933 Cushing moved to Yale as Sterling Professor of Neurology from (1933-1937) and also was made Director of Studies in the History of Medicine. There he published selections from his war diaries, completed an extensive monograph on the meningiomas, and made plans for leaving his library of some 8.000 items, many of great rarity, to Yale University. The establishment of the Medical Library at Yale in 1941 was largely due to the efforts of Cushing and his friends, Dr. Arnold Carl Klebs (1870-1943) of Switzerland and John Farquhar Fulton (1899-1960), a Yale physiologist. Calling themselves “The Tritarians” these three great figures of twentieth-century medicine, together with other friends with smaller collections, gave their extensive library collections to Yale to form the nucleus of one of the great medical historical libraries of the world. John Fulton later received the Pulitzer Prize for his biography of Cushing.

The list of Cushing's honours, honorary doctorates and other distinctions fills several pages. He was awarded honorary degrees from nine American and thirteen European universities; several decorations: Distinguished Service Medal, Companion of the Bath, Officier de la Légion d’Honneur, and order of El Sol del Perú; and many prizes and awards. He was a member of the American Philosophical Society, the National Academy of Sciences, and the American Academy of Arts and Sciences; a foreign member of the Royal Society; and a member, often honorary, of more than seventy medical, surgical, and scientific societies in the United States, South America, Europe, and India. Some thirty-five of his young associates formed the Harvey Cushing Society in 1932; it is now called the American Association of Neurological Surgeons

In 1939, as a surgeon, he was made an Honorary Fellow of the Royal College of Physicians in London. Cushing wrote and thanked. This is from a letter written by the secretary of the Royal College in reply to Cushing's letter:

"I had a fleeting glance at your welcome reply to the President, and saw that you were interested to know whether a surgeon had ever before enjoyed the honour. No, the distinction is yours alone. King Edward VII, when Prince of Wales, was elected an Honorary Fellow in 1897; and in 1928, to mark the auspicious occasion of the Tercentary of the publication of Harvey's De motu cordis, the College elected four Honorary Fellows, namely, Lord Balfour, Lord Rutherford, Professor Pavlov and Professor Wenckebach. Of these, professor Wenkebach is happily with us. You are the only other Honorary Fellow. It will be an additional interest to you to know that, including yourself, only six individuals have enjoyed the distinction of Honorary Fellowship in the course of two and a half centuries."

The four honorary fellows referred to are the then former British foreign minister Arthur James Balfour, 1st Earl of Balfour (1848-1930), the physicist Ernest Rutherford (1871-1937), the Russian experimental physiologist Ivan Petrovich Pavlov (1849-1936), and the Dutch-born Austrian internist Karel Frederik Wenckebach (1864-1940).

Greatest of neuro surgeons
In the USA Cushing is generally recognised as a pioneer, maybe the greatest in neuro surgery. Although he improved and developed several surgical procedures, there is no particular "Cushing surgical procedure", but it is obvious that he, more than any other, proved the feasibility of intracranial surgery. Besides, he was exceptionally considerate to his patients, which came from all over the USA and from Europe, some of them prominent figures. He seems to have spent an enormous lot of time on his surgical activities, for periods operating every day, and, to the despair of his staff, not infrequently even on Saturdays and Sundays.

Cushing contributed to the study of blood pressure during surgery and developed the method of local anaesthesia during surgery. He improved techniques and introduced, among others, the transphenoidal method of operation. His most brilliant achievements, however, were in the treatment of brain tumours, operations that had previously almost invariably led to the death of the patients. Cushing's neurosurgical skills reduced the rate of mortality at brain surgery from some 90 % to approximately 8 %, skills brilliantly demonstrated when, in 1910, he was called upon to operate on Major General Leonard Wood, Chief of Staff of the U.S. Army, to remove a large meningioma. The general returned to his official duties within a month and served throughout World War I and finally became Governor of the Philippines.

Cushing’s extraordinary achievement (based on a series of more than 2.000 verified cases of tumor) of reducing mortality from almost 100 percent to less than 10 percent would have been impossible without early and continuing recourse to the experimental laboratory. He was responsible for establishing the Hunterian Laboratory at Johns Hopkins in 1905 and also the Laboratory of Surgical research at Harvard. Not only did they afford a place for his own investigations, but his course in operative surgery for students, begun in 1902, was basic to another of his important contributions - the training of a generation of surgeons who have extended the boundaries of neurosurgery. From these laboratories came more than 325 papers by his pupils.

Cushing was highly estimated by his colleagues in neuro surgery, and at the gatherings of the Harvey Cushing Society, established 1932, brought together several of the world's greatest neuro surgeons.

In September 1926, occasioned by Cushing receiving the prestigious Cameron Prize for 1924-1925, and giving his three obligatory lecture at the University of Edinburgh, London Hospital gazette wrote:

"There can be few more interesting figures in the surgical world of today than Professor Harvey Cushing. Starting out some twentyfive years ago to specialize in the surgery of the brain, Dr. Cushing rapidly attained a position of great distinction. The way in which it was done can be gathered from a study of his Cameron Lectures, now issued in book form ... His distinction is - and it is a distinction which places him for all time in the front rank of scientific investigators, and his almost unique position among surgical specialists - his distinction is that he has regarded and studied his specialty from every conceivable angle ... Here is the right kind of specialist fit to join such former Cameron Prizemen as Pasteur, Lister, Horsley. Si sic omnes!"

Certain technical problems had to be solved before brain surgery could be successful. In Switzerland in 1900-1901 Cushing studied the blood-pressure-spinal-pressure problem and demonstrated in a classic experiment that as the spinal fluid pressure of a dog is increased, there is initially a vagal effect with bradycardia followed by a high rise in arterial blood pressure. This finding started physiologists such as Walter Cannon on years of further study; for Cushing it made possible safer craniotomes.

In 1901 Cushing visited the University of Pavia, where he met Scipione Riva-Rocci (1863-1937) and became familiar with Riva-Rocci’s apparatus – the mercury sphygmomanometer. He took back to America a model of the apparatus, and was instrumental in its adoption.

The management of haemorrhage was most important, and for this Cushing devised silver clips still used to control bleeding. In 1925 he introduced electrocautery in brain surgery and was able to call back many patients whose tumours he had not dared earlier to attack.

The man and the physician
With his patients Cushing was almost charming, friendly and compassionate, never in a hurry of any kind. To his fellow workers, however, Cushing could be an extremely exasperating and hard task master. His sarcasm and stormy outbursts occurred most frequently in the operating theatre when he would reduce student nurses to tears (sometimes he apologised).

One frequently told story about Cushing is that during his Johns Hopkins days when exchanging stories on Paris with William George MacCallum (1874-1944), Cushing casually remarked "let us meet at the top of the Eiffel Tower ten years from now on July 4th at 2.00 in the afternoon, and continue this conversation". The incident was not mentioned again. MacCallum went to Paris and went to the top of the Eiffel Tower but could not find Cushing; he then noticed an iron staircase which went up to the very top; on clambering up, he was greeted from a small lookout with "Well, Willy, I had almost despaired of you getting here."

In his time, the Mecca of neuro surgery was in his clinics. His social circle and his correspondence with colleagues all over the world were intense - the majority of them also being his students. Numerous travels helped to uphold the contact.

Cushing's unique position in medical establishment is even more conspicuous when judged from his circle from outside neuro surgery. He was visited by Ivan Pavlov (1849-1936), Theodor Kocher (1841-1917), Archibald Vivian Hill (1886-1977) and Lord Charles Sherrington (1857-1952), all recipients of the Nobel Prize for Physiology or Medicine, and he also visited some of them in their own countries. His correspondence with them often lasted for many years. Fulton's detailed account of Cushing's circle in this respects reads like a "Who is who in science?". His broad knowledge of many fields of medicine, maybe most of all the history of medicine, contributed to this standing.

Even outside medicine he devoted himself to wide interests giving incitements to visits and correspondence. He was an excellent illustrator, leaving a large collection of drawings of people he had met. He was also an accomplished writer, and many consider his book Life of Sir William Osler (1925) his most brilliant work. It is one of the finest works in medical biography, and won him the Pulitzer Prize for 1926. He was also a great collector of books, and his large and valuable book collection, particularly on the history of medicine, was to become the basis for the Historical Library at Yale. This was taken over by John Fulton after the death of Cushing.

Cushing died while working on a monograph on the 1600th century anatomist Andreas Vesalius, in which he took a great interest through most of his active life. The heart attack which killed him was triggered as he lifted a heavy folio volume of Vesalius's work.

Handsome and of wiry grace, Harvey Cushing maintained his slight figure through life by moderate participation in sports - baseball in college, tennis in later years. Cushing contracted influenza during the pandemic of 1918 and thereafter suffered from chronic disability, which prevented him from taking more than a few steps at a time.

Cushing died on October 7, 1939 at the age of 70 of myocardial infarction. Autopsy showed a posterior coronary occlusion, complete occlusion of the femoral artery on both sides and, in line with the belief that doctors often develop the disease in which they have specialized, a 1 cm colloid cyst of the third ventricle.

A 1988 United States stamp and postcard feature a portrait of Harvey Cushing, the first person in the United States to use X rays for the diagnosis of neurological problems.

Some quotations

"His death was not the end. Harvey Cushing, like a truly great teacher, had merely turned over his work to his pupils in clinics and operating rooms the world over.

“He was recognised as perhaps the ablest man in his class at the medical school and was an extremely hard worker. As house officer I was his junior and suffered severely in that position for a year. He was an extremely hard man to work with, whether one was over him or under him, as his tremendous ambition for success made it impossible for him to allow anyone else to get any credit for work done. As you know, when he wanted to be he was one of the most charming people in the world, but working with him I found that he couldn’t tolerate anyone else in the limelight." Franklin S. Newell, who served under Cushing at the Massachusetts General Hospital, and later became professor of obstetrics at Harvard. 1942.

“As a research man he was of the deductive type of mind. Some investigators gather their data and try to draw their conclusions from them. He was inclined to have a theory and then use all of his efforts and ingenuity to prove the validity of it... Cushing's interpretation of certain facts which were produced experimentally under his direction undoubtedly has been rather too enthusiastic and has been and will be questioned. When he was reminded of these facts by some of his contemporaries, he usually remarked: 'I never expected to settle these things; I had set others thinking about them and this is the main purpose, after all'." Cushing's associate and admirer, Conrad Jacobsen, on Cushing as a research scientist.

"As an investigator Harvey Cushing had conspicuous faults as well as obvious virtues. In the papers on posterior pituitary secretion he had been led astray, but despite an imposing array of evidence to the contrary, he never really admitted that he had been wrong; in addition, he unfortunately caused a number of his junior associates to waste valuable time and effort in attempting to establish his original contention. It was a curious foible in a man who had achieved so much in so many directions." John Fulton

«To the medical profession, if not to the community in general, The Dispensary [by Samuel Garth, 1661-1718] must always remain of historic import, commemorating as it does the first attempt to establish those out-patient rooms, which since have become such a universal charity.» Quoted by Mary Lou McDonough in Poet Physicians

«We are tending to become a standarized country, and it is perhaps on standardization that industrial progress is founded. But standardization of our education system is apt to stamp out individualism and defeat the very ends of education by leveling the product down rather than up. The qualities that really count in this world are quite beyond pigeonholing, quite beyond measurement by scales, tape, or mental tests, quite beyond rating by any known system of examination, all of which fail in giving us an estimate of that most precious of all qualities, personality. The capacity of the man himself is only revealed when, under stress and responsibility, he breaks through his educational shell and he may then be a splendid surprise to himself no less than to his teachers.» Consecratio Medici, Ch. 1.

«Who have made the greatest gifts to their fellow man? Those who have left an idea that has supplied, like the utterances of Christ, what minds have yearned for? Those who have added to his physical comforts and have found ways to lessen hunger and want? Those who have added to his conveniences and devised means to lighten his labor? Those who have, like Lincoln, freed him from bondage and like Lister released him from the horror of suppuration? One answer certainly can be made: that only when the gift requires self-denial and only if the giver be one that walketh uprightly, and worketh rigteousness and speaketh the truth in his heart, will he, like Saint Francis, come to be canonized and forever blest.» Consecratio Medici, Ch. XIV.

«A physician is obligated to consider more than a diseased organ, more even than the whole man - he must view the man in his world.» Quoted by René J. Dubos in Men Adapting, Ch. XII.

There is only one ultimate and effective preventive for the maladies to which flesh is heir, and that is death.» The Medical Career and Other Papers, «Medicine at the Crossroads.

«In spite of all the discouraging things they are permitted to learn about the units composing society, the doctor and the priest continue to have not only hope for but faith in their fellow men, and expect them, in spite of their frailties, to be unselfish and honest till they prove themselves otherwise; whereas in trade, politics, and the law, we are told, a man is primarily taken to be self-seeking until he proves the contrary.» The Medical Career and Other Papers, «Medicine at the Crossroads.

«Why not put the surgical age of retirement for the attending surgeon at sixty and the physician at sixty-three or sixty-five, as you think best? I have an idea that the surgeon’s fingers are apt to get a little stiff and thus make him less competent before the physicians cerebral vessels do. However, as I told you, I would like to see the day when somebody would be appointed surgeon somewhere who had no hands, for the operative part is the least part of the work. Then, of course, many of us may get vascularly speaking, a little inelastic well on this side of sixty, or may remain in this respect as youthful at seventy as are others at fifty. This is all a lottery of inheritance and habits, and I shall be very glad, for one, to have legislated to stop active work at sixty.» Letter to Dr. Henry Christian, November 20, 1911.

«In these days when science is clearly in the saddle and when our knowledge of disease is consequently advancing at a breathless pace, we are apt to forget that not all can ride and that he also serves who waits and who applies what the horseman discovers.» Consecratio Medici, Ch. 1

We thank Roberto Knerich for correcting an error in the original entry.

A full bibliography of Cushing’s publications was published anonymously by the Harvey Cushing Society in 1939. A reference copy is in the library of the Royal College of Surgeons of England, inscribed and presented by Harvey Cushing. It is entitled A Bibliography of the Writings of Harvey Cushing Prepared on the Occasion of his Seventieth Birthday April 8, 1939 by the Harvey Cushing Society. Attached to the RCS copy is a letter from John Fulton noting that the anonymous compilers were, in fact, Louise Eisenhardt, Madeline Stanton and John Fulton Himself.

  • A method of total extirpation of the Gasserian ganglion for trigeminal neuralgia, by a route through the temporal fossa and beneath the middle meningeal artery. Journal of the American Medical Association, Chicago, 1900, 34: 1035-1041.
  • On the avoidance of shock in major amputations by cocainization of large nerve-trunks preliminary to their division. Annals of Surgery, Philadelphia, 1902, 36: 321-345.
  • On routine determination of arterial tension in operating room and clinic. Boston Medical and Surgical Journal, 1903, 148: 250-256.
  • Pneumatic tourniquets: With special reference to their use in craniotomies. Medical News, 1904, 84: 577-580. First report of tourniquet with pneumatic pressure of measurable degree. This inflatable cuff was the forerunner of the modern technique used generally in surgery.
  • Concerning surgical intervention for the intracranial hemorrhages of the new-born. The American Journal of the Medical Sciences, Phildelphia,1905, 130: 563-581. Successful operative intervention in intracranial haemorrhage of the new-born.
  • The establishment of cerebral hernia as a decompressive measure for inaccessible brain tumors. Surgery, Gynecology and Obstetrics, Chicago, 1905, 1: 297-314.
  • Sexual infantilism with optic atrophy in cases of tumor affecting the hypophysis cerebri. Journal of Nervous and Mental Disease, Chicago, 1906, 33: 704-716.
  • Surgery of the head. In: Surgery, Its Principles and Practice, edited by William Williams Keen, 3: 17-276. Philadelphia, W. B. Saunders, 1908. Cushing's first treatise on neurosurgery. “As a result of this detailed monograph, neurological surgery became almost at once recognized as a clear-cut field of surgical endeavour” (J. F. Fulton, Harvey Cushing [1947] 268).
  • Some aspects of the pathological physiology of intracranial tumors. Boston Medical and Surgical Journal, 1909.
  • The functions of the pituitary body. American Journal of the Medical Sciences, Philadelphia, 1910, 139: 473-484.
  • The special field of neurological surgery: Five years later. Bulletin of the Johns Hopkins Hospital, Baltimore, 1910, 21: 325-339.
  • The Pituitary Body and its Disorders. Clinical States produced by Disorders of the Hypophysis Cerebri. Philadelphia, J. B. Lippincott, 1912. 350 pages with 319 figures and detailed reports on 50 patients with endocrine disturbance of the gland. The textual matter, case histories, and illustrations in this pioneer work have scarcely been improved upon to this day. This landmark in endocrinology also includes Cushing’s pioneering method of operating on tumours of the pituitary.
  • Tumors of the Nervus Acusticus and the Syndrome of the Cerebello-pontile Angle. Philadelphia, W. B. Saunders, and London, 1917. Reprinted 1963. This book consists primarily of detailed and well-illustrated case histories of patients with surgically challenging lesions of the brain stem. It reveals the carefully documented case histories Cushing kept and the self-discipline with which he worked.
  • A study of a series of wounds involving the brain and its enveloping structures. British Journal of Surgery, London, 1918, 5: 558-684.
  • The special field of neurological surgery after another interval. Archives of Neurology and Psychiatry, Chicago, 1920, 4: 603-637.
  • The Life of Sir William Osler. 2 volumes. Oxford, Clarendon Press, 1925.
  • Studies in Intracranial Physiology & Surgery. London, 1926. Cushing delivered the three papers in this book as the Cameron Prize Lectures at the University of Edinburgh in October 1925. The three lectures were: 1. The third circulation and its channels. 2. The pituitary gland as now known. 3. Intracranial tumours and the surgeon. Very little is known about the founder of these lectures, Andrew Robertson Cameron. He was born in Torland, Aberdeenshire, and completed his medical studies at Edinburgh in 1861. He emigrated to Australia, settled in New South Wales, and died there in 1878.
  • A Classification of the Tumors of the Glioma Group on a Histogenic Basis with a Correlated Study of Prognosis. Written with Percival Bailey. Philadelphia, London and Montreal, J. B. Lippincott Company, 1926. 121 pages. With 108 illustrations. First German translation by A. Cammann: Die Gewebsverschiedenheiten der Hirngliome und ihre Bedeutung für die Prognose. Jena, Gustav Fischer Verlag, 1930.
  • The Meningiomas Arising from the Olfactory Grove and their Removal by the Aid of Electro-surgery. Glasgow, 1927.
  • Tumors Arising from the Blood-Vessels of the Brain: Angiomatous Malformations and Hemangioblastomas. With Percival Bailey. Springfield, Illinois and Baltimore, C.C.Thomas, 1928. This monograph contains the first extensive classification and description of angiomatous malformations and hemangioblastomas. The detailed and profusely illustrated case reports are, like all of Cushing's case reports, a course of instruction in themselves.
  • Electro-surgery as an aid to the removal of intracranial tumors. With a preliminary note on a new surgical-current generator by W. T. Bovie. Surgery, Gynecology and Obstetrics, Chicago, 1928, 47: 751-784. Bovie is the physicist Dr. William Bovie, who in 1926 worked with Cushing when the latter used the high-frequency current to remove a vascular myeloma invading the scalp.
  • Consecratio Medici and Other Papers. Essays, Boston, 1928.
  • The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bulletin of the Johns Hopkins Hospital, Baltimore, 1932; 50: 137.
  • Intracranial Tumors. Springfield, Illinois, C. C. Thomas, 1932. Cushing’s operating technique reduced the mortality rate dramatically in intracranial surgery. This was his last published report on the statistical results of brain tumours as a whole.
  • Papers Relating to the Pituitary Body, Hypothalamus and Parasympathetic Nervous System. Springield Illinois, C. C. Thomas, 1932. The four papers in this volume were "brought together for the convenience of those whom the general theme might interest." The papers had all been published elsewhere and were the basis for four different lectures Cushing had given in England, Canada and America during the years 1930 to 1932.
  • Intracranial Tumours; Notes upon a Series of Two Thousand Cases with Surgical-Mortality Percentages Pertaining Thereto. Springfield, Illinois, 1932. The material covered in this book formed the basis of a report Cushing made to the International Neurological Congress in Berne, Switzerland on September 1, 1931.
  • From a Surgeon’s Journal, 1915-1918. Boston, 1936.
  • Meningiomas. Their Classification, Regional Behaviour, Life History and Surgical End Results. With the collaboration of Louise Charlette Eisenhardt (1891-1967). Springfield, Illinois, Charles C. Thomas, 1938. Reprint in two volumes: New York, Hafner, 1962. "The present treatise was commenced in 1915 soon after the completion of his volume on the pituitary disorders, and it therefore represents nearly twenty-five years of work; by common consent it is regarded as Dr. Cushing's greatest clinical monograph. It is the embodiment of all the things he has stood for during his career as a clinician: his painstaking case records and photographs, his unusual artistic ability evident in his own numerous operative sketches, and his extraordinary knowledge of the day to day life of his patients" (Harvey Cushing Society). Dr. Eisenhardt, nurse, physician, brilliant neuropathologist, and devoted friend and colleague of Dr. Cushing, collaborated in the publication of the work, and her microphotographs easily support the classification used in this most exhaustive work on the subject of intracranial meningiomas.
  • Bibliography of Andreas Vesalius. 1943. 2nd edition, Hamden, Connecticut, 1962. A third edition has later appeared.
  • The Harvey Cushing Collection of Books and Manuscripts. New York, Schuman’s, 1943. Catalogue, without annotations, of the books and manuscripts bequeathed by Cushing to the Historical Library in the Cushing/Whitney Medical Library at the Yale University School of Medicine. Harvey Cushing and E. C. Streeter edited a facsimile edition of Giovanni Battista (Giambattista) Canano’s (1515-1579) work Musculorum humani corporis picturata dissectio, first printed (probably) in Ferrara, 1541. Facsimile edition, Florence, 1925. With John Homans (1877-1954), Cushing was co-author of Samuel James Crowe’s (1883-1955) article Experimental hypophysectomy. Johns Hopkins Hospital Bulletin, 1910, 21: 127-169. This book gave the first experimental evidence of the relationship between the pituitary and the reproductive system. See also:
  • H. Schloffer: Erfolgreiche Operation eines hypophysen Tumors auf nasalem Wege. Wiener klinische Wochenschrift, 1907, 20: 621-624, 670-671, 1075-1078. Schloffer’s operation by the nasal route.
  • John F. Fulton: Harvey Cushing. A biography. Springfield, Illinois, C. C. Thomas, 1946.
  • R. M. Goldwyn: Bovie: The man and the machine. Annals of Plastic Surgery, Boston, 1979, 2: 135-153.
  • Jeremiah A Barondess: Cushing and Osler: The Evolution of a Friendship. Transactions and Studies of the College of Physicians of Philadelphia, 1985, 7: 79-112.
  • N. P. Hirsch, G. B. Smith: Harvey Cushing: his contribution to anaesthesia. Anesthesia and Analgesia, New York, 1986, 65: 288-293.
  • Peter M. Black, editor: Harvey Cushing at the Brigham. American Association of Neurological Surgeons, 1993.

Friday, April 2, 2010

Researchers quantify benefits of minimally invasive removal of hard-to-reach tumors

A minimally invasive endoscopic procedure holds promise for safely removing large brain tumors from an area at the bottom of the skull, near the sinus cavities, clinical researchers at the Brain Tumor Center at the University of Cincinnati Neuroscience Institute (UCNI) at University Hospital have found.

The findings, to be published in the April 2010 issue of the Journal of Neurosurgery and previously published online in October 2009, have important implications for patients with large pituitary tumors (pituitary macroadenomas).

"This is the first time that a quantitative advantage has been shown for the use of endoscopy in cranial surgery," says Philip Theodosopoulos, MD, principal investigator of the study, director of skull base surgery at UC and a neurosurgeon with the Mayfield Clinic.

"This signals the dawn of a new era in minimally invasive cranial surgery. We have moved from the realm of assessing whether it is feasible to studying its clinical effectiveness. In this way, it is slowly starting to change from a novelty to standard treatment, setting the bar for the quality of surgical outcomes higher than ever before."

Although tumors of the pituitary gland, located near the base of the skull, are benign, pituitary macroadenomas can wreak havoc, causing acromegaly (an overproduction of growth hormone), Cushing disease (an overproduction of the hormone cortisol) and hyperthyroidism, as well as visual problems, headaches and dizziness.

When removing pituitary macroadenomas (tumors that are larger than 10 millimeters), surgeons have employed three distinct routes to the tumor:

  • Through the skull, in a procedure called a craniotomy.
  • Through an incision under the upper lip and then through the septum, which must be split apart.
  • Through the nostrils -- a transnasal approach -- without an incision.

The endoscopic transsphenoidal approach, Theodosopoulos says, follows natural anatomical corridors and causes less disruption of nasal tissues. This approach, as the new study reveals, also holds benefits related to complete tumor removal, which is important for the patient's quality of life.

Removing an entire pituitary macroadenoma can be difficult because the tumor's growth pattern can cause it to extend through the sinus corridor, which is out of the surgeon's view.

Surgeons can ensure that the entire tumor has been removed if their hospital operating room is equipped with a technology known as intraoperative MRI, or ioMRI. The surgery-prolonging technology enables surgeons to take MRI scans while the patient is still under anesthesia and on the operating table. The UC Neuroscience Institute at University Hospital has had ioMRI since 1999, but the expensive technology is not available at most hospitals.

An endoscopic approach, by contrast, allows the surgeon to check for remaining tumor with "intrasellar endoscopy." Using a tiny, sophisticated camera on an angled endoscope, the surgeon can peer around bends and into crevasses to identify any remaining tumor. "The endoscopic approach holds the potential for less invasive treatment for all patients and more complete tumor resections for individuals treated in hospitals without access to intraoperative MRI," Theodosopoulos says.

During the retrospective study at University Hospital, the team analyzed surgical outcomes of 27 consecutive patients between 2005 and 2007 who had undergone endoscopic removal of pituitary macroadenomas. The search for unexpected residual tumor was conducted two ways in all patients: first with the tiny endoscopic camera (intrasellar endoscopy) and then with intraoperative MRI.

Following the initial endoscopic tumor removal, intrasellar endoscopy revealed that 23 of the 27 patients (85 percent) had no unexpected residual tumor. Surgeons were able to safely perform additional surgery on three of the four patients who had unacceptable residual tumor.

Following the endoscopic procedures, all patients were checked with intraoperative MRI, which revealed that tumor removal was successful in 26 patients (96 percent).

The study results show that maximum tumor removal can be successfully achieved with endoscopy and without intraoperative MRI, Theodosopoulos says. He adds, however, that the findings could be strengthened by a larger study.

Provided by University of Cincinnati Academic Health Center