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An Update on Pituitary Surgery for Cushing’s Disease

IntroductionQuestions to ask Neurosurgeon

Although there are now several new methods for the medical management of Cushing’s disease, for patients who have progressive severe signs and symptoms, surgery provides the best chance of a long lasting remission. Making the diagnosis of a pituitary tumor secreting excess levels of ACTH as the cause of Cushing’s disease can be complicated, but is essential before proceeding to surgery. These tumors are often very small in size. The type of surgery recommended is usually through a nasal approach, called transsphenoidal surgery. Although many neurosurgeons have extensive experience in neck, spine and brain surgery, significant experience with the diagnosis and treatment of Cushing’s disease is extremely important for successful treatment. This applies to both the endocrinologist and the neurosurgeon involved. Standards for Pituitary Centers of Excellence have been proposed, and these specialty centers generally include neurosurgeons who operate on as many as 50 or more pituitary tumors per year, and endocrinologists with similar experience.4 In the hands of experienced pituitary neurosurgeons, successful remission of Cushing’s disease occurs in 70-90% of patients after surgery. Although these tumors are almost always benign, recurrences can develop, and long term follow-up is required.

How is Pituitary Surgery Done?

Cushing’s tumors are generally small, whereas other types of pituitary tumors can be significantly larger. Each presents a unique surgical challenge. Small tumors can be difficult to locate; large tumors may be invasive in nature and can be difficult to remove completely.

Very rarely, Cushing’s disease may be related to a large pituitary tumor (macroadenoma). These unusual tumors can be operated upon by a craniotomy, or with the use of the intraoperative MRI.

The vast majority of tumors in Cushing’s disease are microadenomas (< 10 mm in diameter), can be seen on modern MRI, and can be detected in approximately 60% of adults and 55% of children with Cushing’s disease. These small tumors are operated on using a minimally invasive trans-nasal transsphenoidal approach. The surgeon uses either the operating microscope or the operating endoscope for visualization, depending on the surgeon’s preference and experience.

The microscope has been used since the late 1960s and has become a highly sophisticated instrument, with the advantage of providing three-dimensional visualization. With this technique, a speculum is introduced through the nostril, providing a narrow but secure route of access to the pituitary area. Most neurosurgeons have been trained to use the microscope for pituitary surgery.

The endoscope was introduced to pituitary surgery in the 1990s, and has also undergone steady improvement. The major advantage of the endoscope is that it provides a broad panoramic view of the pituitary area and surrounding structures. The endoscope can provide either 2-D or 3-D visualization and a close view of the pituitary tumor and the normal pituitary gland.

By far the most important factor in selecting a pituitary neurosurgeon is the surgeon’s experience with Cushing’s tumors, not whether the microscope or endoscope will be used for the procedure.

In many centers, an ENT surgeon is involved in performing the approach, particularly if there has been prior nasal surgery, a nasal septal deviation, or other issues related to the nasal anatomy. An ENT surgeon familiar with the operation can also be helpful in dealing with nasal issues post-surgery.

In some cases, an abdominal fat graft taken from a small area under the umbilicus is used to fill the space left after removing the tumor, or to seal a spinal fluid leak. Nasal packing is occasionally necessary, but with current techniques is not routinely applied.

The usual uncomplicated surgical operation, done under general anesthesia lasts 3 to 4 hours. In most patients, postoperative care in the ICU is not necessary.

What should be expected after pituitary surgery for Cushing’s disease?

In successful surgery, cortisol levels decrease over a few days. This is checked with frequent blood levels. As soon as they are shown to be very low, patients may have headache, nausea and fatigue requiring cortisol replacement. Other pituitary hormones such as thyroid levels may be affected by surgery; these can be replaced with medication with the help of an endocrinologist. The usual hospital stay is about 3 days. Recovery from all of the symptoms of Cushing’s disease is often slow, and can take many months.

What is the future of pituitary surgery?

In addition to the development of new advances in medical therapy, many exciting prospects for the future involve better detection of the small tumors producing Cushing’s disease. New MRI methods include those with a major increase of sensitivity of detection using a 7T MRI instrument. Another MRI technique called MR elastance can help determine whether a tumor is firm or soft in consistency. A new technique called MALDI spectroscopy shows promise in detecting areas of the pituitary gland where the ACTH tumor cells are clustered. New metabolic imaging techniques using an isotope specific to neuroendocrine tumors may be very helpful in detecting sources of excess ACTH in the pituitary and elsewhere in the body (ectopic sources). Technical advances in visualization such as the 3D endoscope may help provide surgeons the ability to perform more precise operations on the pituitary gland.


  1. Barkhoudarian G, Becerra Romano A, Laws ER. Evaluation of the three dimensional endoscope in transsphenoidal surgery. Neurosurgery. 2013
  2. Dunn IF, Laws ER Jr. The surgical management of Cushing’s disease. Bronstein MD (ed). In: Cushing’s Syndrome: Pathophysiology, Diagnosis and Treatment. Humana Press: 2009. p. 121-30
  3. Laws ER, Starke RM, Reames DL, Chen CJ, Jane JA Jr. Endoscopic transsphenoidal surgery for Cushing’s disease. Neurosurgery. 2013; 72:420-427
  4. McLaughlin, N, Laws ER, Oyesiku N, Katznelson L, Kelly DF. Pituitary centers of excellence. Neurosurgery 2012; 71:916-26
  5. Starke RM, Reames DL, Ching-Jen C, Laws ER, Jane JA. Endoscopic transsphenoidal surgery for Cushing disease: techniques, outcomes, and predictors of remission. Neurosurgery. 2013: 72: 240-247.

By Edward R. Laws, MD, FACS and Sherry L. Iuliano, NP-C, Winter, 2016

Editor’s Note: Dr. Edward Laws is the Surgical Director of the Pituitary and Neuorendocrine Center at Brigham and Women’s Hospital, and Professor of Neurosurgery at Harvard Medical School. Dr. Edward Laws has performed over 5,800 transsphenoidal operations for pituitary disorders. Sherry Iuliano is the Nurse Practitioner for Dr. Laws.

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