Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 153-159 ◽  
Author(s):  
Guenther Christian Feigl ◽  
Karin Pistracher ◽  
Andrea Berghold ◽  
Michael Mokry

Object Causes of pituitary insufficiencies as a side effect of Gamma Knife surgery (GKS) following irradiation of the hypothalamopituitary axis are still under debate. In an investigation of pituitary insufficiencies after GKS, the authors' main focus is on what role can be attributed to the hypothalamus with regard to endocrinological changes in hypothalamopituitary function following GKS. Methods A total of 108 patients consecutively treated between April 1992 and July 2003 were included in this retrospective study. All patients had undergone either transsphenoidal or transcranial surgery prior to GKS. The spot dosimetry method was used to determine doses delivered to structures of the hypothalamopituitary axis. For statistical analyses, endocrine insufficiency and deterioration in pituitary function were defined as a decrease in hormonal blood levels below the normal range for 1 or more anterior pituitary lobe hormones. Additionally, an analysis of the rate of patients requiring hormone replacement therapy after GKS due to new endocrinopathies was performed. Results Complete patient records of 61 male and 47 female patients with a mean age of 51.9 years (range 9.1–81.2 years) were available for our investigation. The overall tumor control rate was 97% and the endocrinological cure rate was 61.2%. Mean treatment doses in patients with and without new endocrine insufficiencies (shown as with/without insufficiencies and followed by probability values) were as follows: 1.3/0.8 Gy to the hypothalamus (p = 0.2); 2.2/1.6 Gy to the median eminence (p = 0.1); 6.5/4.1 Gy to the pituitary stalk (p = 0.004); and 12.4/9.5 Gy to the pituitary gland (p = 0.05). The median overall duration of follow-up after GKS was 6.7 years, with 84 patients (77.7%) whose follow-up was longer than 12 months. The median follow-up time after GKS in patients who developed a new pituitary dysfunction was 79.5 months (6.6 years, SD 3.8 years), and the median follow-up time in patients with no new insufficiencies was 78.4 months (6.5 years, SD 4 years). Conclusions Gamma Knife surgery is a safe and effective treatment for patients with residual and recurrent pituitary adenomas. The rate of pituitary insufficiencies after GKS is still lower than that after conventional radiotherapy. Very low radiation doses are directed to the hypothalamus, and thus this structure does not play a major role in the development of pituitary insufficiencies after GKS. The results of this study show that patients in whom the pituitary stalk and pituitary gland receive a high mean point dose are more likely to develop pituitary insufficiencies after GKS than those who receive a lower dose.

2006 ◽  
Vol 105 (Supplement) ◽  
pp. 26-30 ◽  
Author(s):  
Mooseong Kim ◽  
Sunghwa Paeng ◽  
Seyoung Pyo ◽  
Yeonggyun Jeong ◽  
Sunil Lee ◽  
...  

ObjectPituitary adenomas have been treated using a variety of modalities including resection, medication, fractionated radiotherapy, and stereotactic radiosurgery. The policy has been that all adenomas should first be treated with resection to reduce the volume of the tumor. The authors' study was conducted to determine the efficacy of using Gamma Knife surgery (GKS) for pituitary adenomas invading the cavernous sinus.MethodsOf 397 patients with pituitary tumors who underwent GKS between October 1994 and October 2005, 68 patients had pituitary macroadenomas invading the cavernous sinus. Sixty-seven cases were available for follow up. The mean age of the patients in these cases was 42.8 years (range 14–73 years). The male/female ratio was 0.8:1. The mean adenoma volume was 9.3 cm3. A total of 24 patients had undergone craniotomies and resection, and 11 patients had undergone transsphenoidal surgery prior to GKS. The mean follow-up period was 32.8 months. Tumor control was defined as a decrease or no change in tumor volume after GKS. Endocrinological improvement was defined as a decline in hormone levels to below 50% of the pre-GKS level.Tumor control was achieved in 95.5% of the cases. Endocrinological improvement was achieved in 68% of 25 patients. One patient suffered hypopituitarism after GKS.Conclusions Gamma Knife surgery is a safe and effective treatment for invasive pituitary macroadenoma with few complications.


2021 ◽  
pp. 1-9
Author(s):  
I. Jonathan Pomeraniec ◽  
Zhiyuan Xu ◽  
Cheng-Chia Lee ◽  
Huai-Che Yang ◽  
Tomas Chytka ◽  
...  

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17–2.68, p = 0.006). CONCLUSIONS SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.


2007 ◽  
Vol 106 (6) ◽  
pp. 980-987 ◽  
Author(s):  
Jay Jagannathan ◽  
Jason P. Sheehan ◽  
Nader Pouratian ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yanli Li ◽  
Lisha Wu ◽  
Tingting Quan ◽  
Junyi Fu ◽  
Linhui Cao ◽  
...  

ObjectiveThis study aimed to report the characteristic of tumor regrowth after gamma knife radiosurgery (GKRS) and outcomes of repeat GKRS in nonfunctioning pituitary adenomas (NFPAs).Design and MethodsThis retrospective study consisted of 369 NFPA patients treated with GKRS. The median age was 45.2 (range, 7.2–84.0) years. The median tumor volume was 3.5 (range, 0.1–44.3) cm3.ResultsTwenty-four patients (6.5%) were confirmed as regrowth after GKRS. The regrowth-free survivals were 100%, 98%, 97%, 86% and 77% at 1, 3, 5, 10 and 15 year, respectively. In multivariate analysis, parasellar invasion and margin dose (<12 Gy) were associated with tumor regrowth (hazard ratio [HR] = 3.125, 95% confidence interval [CI] = 1.318–7.410, p = 0.010 and HR = 3.359, 95% CI = 1.347–8.379, p = 0.009, respectively). The median time of regrowth was 86.1 (range, 23.2–236.0) months. Previous surgery was associated with tumor regrowth out of field (p = 0.033). Twelve patients underwent repeat GKRS, including regrowth in (n = 8) and out of field (n = 4). Tumor shrunk in seven patients (58.3%), remained stable in one (8.3%) and regrowth in four (33.3%) with a median repeat GKRS margin dose of 12 (range, 10.0–14.0) Gy. The actuarial tumor control rates were 100%, 90%, 90%, 68%, and 68% at 1, 3, 5, 10, and 15 years after repeat GKRS, respectively.ConclusionsParasellar invasion and tumor margin dose (<12 Gy) were independent risk factors for tumor regrowth after GKRS. Repeat GKRS might be effective on tumor control for selected patients. For regrowth in field due to relatively insufficient radiation dose, repeat GKRS might offer satisfactory tumor control. For regrowth out of field, preventing regrowth out of field was the key management. Sufficient target coverage and close follow-up might be helpful.


2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 44-47 ◽  
Author(s):  
Cheng-Loong Liang ◽  
Kang Lu ◽  
Po-Chou Liliang ◽  
Han-Jung Chen

Optic pathway/hypothalamic gliomas represent approximately 2%–5% of brain tumors in children. Total excision, subtotal excision, subtotal excision followed by irradiation, radiation therapy alone, chemotherapy, and no treatment at all have been reported. In this article the authors discuss the results of Gamma Knife surgery (GKS) for optic gliomas in 2 children. Two pediatric patients, a boy and a girl, underwent GKS for optic gliomas at our hospital between March 2005 and August 2005. The children's ages were 10 and 16 years at presentation. The histological diagnosis was confirmed to be pilocytic astrocytoma in both cases. The tumor involved the optic chiasm in 1 patient and the right optic nerve in the other patient. Treatments were planned with the prescription of 11 Gy to the 50% isodose line for the optic chiasm glioma and 15 Gy to the 50% isodose line for the optic nerve glioma. In both patients, GKS was well tolerated. The follow-up periods were 60 and 55 months. Complete response with near-total disappearance of the tumors was observed in both patients. During the follow-up period, neither of the patients developed any endocrine dysfunction. Gamma Knife surgery permits treatment of optic glioma with good tumor control and no clinically relevant morbidity. With the ability to deliver a high dose to the tumor while sparing normal brain tissue, especially the optic nerve, optic chiasm, and pituitary gland, GKS should be the choice of treatment for optic gliomas. A larger number of patients and long-term follow-up are required for further evaluation of the efficacy and potential side effects of GKS.


2006 ◽  
Vol 105 (Supplement) ◽  
pp. 91-98 ◽  
Author(s):  
Guenther Christian Feigl ◽  
Gerhard A. Horstmann

ObjectBrain metastases are diagnosed in 20 to 40% of all cancer patients and are associated with a considerable drop in life expectancy and often also in quality of life for these patients. Several treatment options are available including surgery, chemotherapy, whole-brain radiotherapy, stereotactic radiotherapy, stereotactic radiosurgery, and Gamma Knife surgery (GKS). However, management of brain metastases still presents a challenge and there is no general consensus on the best treatment strategy. The aim of the authors' study was to further evaluate the efficacy of GKS in the treatment of brain metastases and to evaluate the predictive value of volumetric tumor follow-up measurement.MethodsConsecutive patients with controlled systemic cancer and variable numbers of brain metastases were included in this prospective study. Patients with severe symptoms of brain compression underwent surgery before GKS. Each follow-up examination included a thorough neurological examination and a neuroradiological quantitative volumetric tumor analysis.A total of 300 consecutive patients (mean age 58 years) with 703 brain metastases were treated between December 1998 and October 2005. The mean total tumor volume (TTV) was 2.1 cm3. The overall local tumor control rate was 84.5%. In 79% of all treated metastases a mean TTV reduction of 84.7% was achieved using a mean prescription dose of 21.8 Gy. Only few, mostly mild, side effects were observed during the mean follow-up period of 12.7 months. The overall mean progression-free survival period was 9.4 months. There was a statistically significant difference in survival of patients with one compared with multiple metastases, regardless of the histological type and preceding treatment.Conclusions Gamma Knife surgery is a safe and effective treatment for patients with brain metastases regardless of the history of treatment and histological tumor type. It achieves excellent tumor control, significant TTV reduction without causing severe side effects, and accordingly, preserves quality of live. Volume changes after GKS did not serve as a predictor for treatment outcome and survival.


2005 ◽  
Vol 102 ◽  
pp. 189-194 ◽  
Author(s):  
Guenther C. Feigl ◽  
Otto Bundschuh ◽  
Alireza Gharabaghi ◽  
Madjid Samii ◽  
Gerhard A. Horstmann

Object.The purpose of this study was to evaluate the volume-reducing effects of gamma knife surgery (GKS) of meningiomas with and without previous surgical treatment.Methods.A group of 127 patients with a mean age of 57.1 years (range 9–81 years) with 142 meningiomas (128 World Health Organization Grade I and 14 Grade II) were included in this study. The management strategy reduces tumor volume with surgery when necessary (81 patients). Stereotactic GKS with a Gamma Knife model C was performed in all tumors of suitable size. Magnetic resonance imaging follow-up examinations with volumetric tumor analysis was performed 6 months after treatment and annually thereafter.The mean tumor volume was 5.9 cm3(range < 5 to > 40 cm3). The mean follow-up time after GKS was 29.3 months (range 11–61 months). The mean prescription dose was 13.8 Gy (range 10–18 Gy). A reduction in volume occurred in 117 (82.4%) of all tumors, and in 20 tumors (14.1%) growth ceased. The overall tumor control rate of 96.4%. The mean volume reduction achieved with GKS was more than 46.1%. Only five tumors (3.5%) showed a volume increase.Conclusions.Gamma knife surgery was effective in reducing meningioma volume at short-term follow up. Further studies are needed to examine the development of these findings over a longer period.


2013 ◽  
Vol 119 (2) ◽  
pp. 446-456 ◽  
Author(s):  
Jason P. Sheehan ◽  
Robert M. Starke ◽  
David Mathieu ◽  
Byron Young ◽  
Penny K. Sneed ◽  
...  

Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1–223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02–1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96–4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.


2013 ◽  
Vol 119 (6) ◽  
pp. 1486-1492 ◽  
Author(s):  
Jason P. Sheehan ◽  
Zhiyuan Xu ◽  
David J. Salvetti ◽  
Paul J. Schmitt ◽  
Mary Lee Vance

Object Cushing's disease is a challenging neuroendocrine disorder. Although resection remains the primary treatment option for most patients, the disease persists if there is residual or recurrent tumor. Stereotactic radiosurgery has been used to treat patients with persistent Cushing's disease after a prior resection. The authors report on the long-term risks and benefits of radiosurgery for Cushing's disease. Methods A retrospective review of a prospectively collected database of radiosurgery patients was undertaken at the University of Virginia. All patients with Cushing's disease treated with Gamma Knife surgery (GKS) were identified. Those without at least 12 months of clinical and radiological follow-up were excluded from this analysis. Rates of endocrine remission, tumor control, and adverse events were assessed. Statistical methods were used to identify favorable and unfavorable prognostic factors. Results Ninety-six patients with the required follow-up data were identified. The mean tumor margin dose was 22 Gy. The median follow-up was 48 months (range 12–209.8 months). At the last follow-up, remission of Cushing's disease occurred in 70% of patients. The median time to remission among all patients was 16.6 months (range 1–165.7 months). The median time to remission in those who had temporarily stopped taking ketoconazole at the time of GKS was 12.6 months, whereas it was 21.8 months in those who continued to receive ketoconazole (p < 0.012). Tumor control was achieved in 98% of patients. New loss of pituitary function occurred in 36% of patients. New or worsening cranial neuropathies developed in 5 patients after GKS, with the most common involving cranial nerves II and III. Conclusions Gamma Knife surgery offers a high rate of tumor control and a reasonable rate of endocrine remission in patients with Cushing's disease. The cessation of cortisol-lowering medications around the time of GKS appears to result in a more rapid rate of remission. Delayed hypopituitarism and endocrine recurrence develop in a minority of patients and underscore the need for long-term multidisciplinary follow-up.


2012 ◽  
Vol 116 (3) ◽  
pp. 598-604 ◽  
Author(s):  
Brian D. Milligan ◽  
Bruce E. Pollock ◽  
Robert L. Foote ◽  
Michael J. Link

Object Gamma Knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors. Methods Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm3 (range 5.3–19.1 cm3). The median maximum posterior fossa diameter was 2.8 cm (range 2.5–3.8 cm). The median tumor margin dose was 12 Gy (range 12–14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26–121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection. Results Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction. Conclusions Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.


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