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Martin H. Weiss

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Jason P. Sheehan, Nader Pouratian, Ladislau Steiner, Edward R. Laws and Mary Lee Vance

Object

Gamma Knife surgery (GKS) is a common treatment for recurrent or residual pituitary adenomas. This study evaluates a large cohort of patients with a pituitary adenoma to characterize factors related to endocrine remission, control of tumor growth, and development of pituitary deficiency.

Methods

A total of 418 patients who underwent GKS with a minimum follow-up of 6 months (median 31 months) and for whom there was complete follow-up were evaluated. Statistical analysis was performed to evaluate for significant factors (p < 0.05) related to treatment outcomes.

Results

In patients with a secretory pituitary adenoma, the median time to endocrine remission was 48.9 months. The tumor margin radiation dose was inversely correlated with time to endocrine remission. Smaller adenoma volume correlated with improved endocrine remission in those with secretory adenomas. Cessation of pituitary suppressive medications at the time of GKS had a trend toward statistical significance in regard to influencing endocrine remission. In 90.3% of patients there was tumor control. A higher margin radiation dose significantly affected control of adenoma growth.

New onset of a pituitary hormone deficiency following GKS was seen in 24.4% of patients. Treatment with pituitary hormone suppressive medication at the time of GKS, a prior craniotomy, and larger adenoma volume at the time of radiosurgery were significantly related to loss of pituitary function.

Conclusions

Smaller adenoma volume improves the probability of endocrine remission and lowers the risk of new pituitary hormone deficiency with GKS. A higher margin dose offers a greater chance of endocrine remission and control of tumor growth.

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Dibyendu Kumar Ray, Chun Po Yen, Mary Lee Vance, Edward R. Laws, Beatriz Lopes and Jason P. Sheehan

Lymphocytic hypophysitis is a relatively uncommon autoimmune inflammatory disorder affecting the pituitary gland. It most frequently occurs in women of child-bearing age. The authors report on their experience with a patient who presented with diplopia and marked enlargement of the pituitary gland. She underwent transsphenoidal surgery, and histopathological analysis confirmed the diagnosis of lymphocytic hypophysitis. The disease proved refractory to resection, and any attempt at withdrawal of corticosteroid therapy resulted in a return of the patient's symptoms and enlargement of the sellar contents.

The patient underwent Gamma Knife surgery (GKS) to the sella and both cavernous sinuses. After GKS, the patient was able to discontinue steroid therapy without return of her symptoms. Follow-up MR images demonstrated no evidence of recurrence of lymphocytic hypophysitis.

For persistent lymphocytic hypophysitis, GKS is a reasonable treatment option.

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William J. Mauermann, Jason P. Sheehan, Daniel R. Chernavvsky, Edward R. Laws, Ladislau Steiner and Mary Lee Vance

Object

Patients with adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas may require a bilateral adrenalectomy to treat their Cushing's disease. Approximately one third of these patients, however, will experience progressive enlargement of the residual pituitary adenoma, develop hyperpigmentation, and have an elevated level of serum ACTH. These patients with Nelson's syndrome can be treated with Gamma Knife surgery (GKS).

Methods

The prospectively collected University of Virginia Gamma Knife database of patients with pituitary adenomas was reviewed to identify all individuals with Nelson's syndrome who were treated with GKS. Twenty-three patients with a minimum of 6 months of follow up were identified in the database. These patients were assessed for tumor control (that is, lack of tumor growth over time) with neuroimaging studies (median follow-up duration 22 months) and for biochemical normalization of their ACTH levels (median follow-up duration 50 months). Neuroimaging follow-up studies were available for 22 patients, and endocrine follow up was available for 15 patients in whom elevation of ACTH levels was documented prior to GKS.

In the 22 patients in whom neuroimaging follow-up studies were available, 12 had a decrease in tumor size, eight had no tumor growth, and two had an increase in tumor volume. Ten of 15 patients with elevated ACTH levels prior to GKS showed a decrease in their ACTH levels at last follow up; three of these 10 patients achieved normal ACTH levels (< 50 pg/ml) and the other five patients with initially elevated values had an increase in ACTH levels.

Ten patients were thoroughly evaluated for post-GKS pituitary function; four were found to have new pituitary hormone deficiency and six did not have hypopituitarism after GKS. One patient suffered a permanent third cranial nerve palsy and four patients are now deceased.

Conclusions

Gamma Knife surgery may control the residual pituitary adenoma and decrease ACTH levels in patients with Nelson's syndrome. Delayed hypopituitarism or cranial nerve palsies can occur after GKS. Patients with Nelson's syndrome require continued multidisciplinary follow-up care. Given the difficulties associated with management of Nelson's syndrome, even the modest results of GKS may be helpful for a number of patients.

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Martin H. Weiss and William T. Couldwell

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Jay Jagannathan, Jason P. Sheehan, Nader Pouratian, Edward R. Laws, Ladislau Steiner and Mary Lee Vance

Object

In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas.

Methods

A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy).

Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes.

Conclusions

Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.

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Jason P. Sheehan, Ajay Niranjan, Jonas M. Sheehan, John A. Jane Jr., Edward R. Laws, Douglas Kondziolka, John Flickinger, Alex M. Landolt, Jay S. Loeffler and L. Dade Lunsford

Object. Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas.

Methods. Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas.

A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low.

Conclusions. Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.

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Jonas M. Sheehan, Mary L. Vance, Jason P. Sheehan, Dilantha B. Ellegala and Edward R. Laws Jr.

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.

Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.

Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.

Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

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Clival encephalocele

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George J. Kaptain, David A. Vincent, Jason P. Sheehan and Edward R. Laws Jr.