Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes

2011 ◽  
Vol 114 (2) ◽  
pp. 303-309 ◽  
Author(s):  
Jason P. Sheehan ◽  
Nader Pouratian ◽  
Ladislau Steiner ◽  
Edward R. Laws ◽  
Mary Lee Vance
Keyword(s):  
Pituitary Adenoma ◽  
Radiation Dose ◽  
Tumor Growth ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Gamma Knife Surgery ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency

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.

scholarly journals Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study

2019 ◽  
Vol 131 (4) ◽  
pp. 1188-1196 ◽  
Author(s):  
Diogo Cordeiro ◽  
Zhiyuan Xu ◽  
Gautam U. Mehta ◽  
Dale Ding ◽  
Mary Lee Vance ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Proportional Hazards Model ◽  
Gamma Knife Radiosurgery ◽  
Cox Proportional Hazards Model ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
New Onset

OBJECTIVERecurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.METHODSSeventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing’s disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6–246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.RESULTSAt last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months.In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).CONCLUSIONSHypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.

Gamma Knife surgery for adrenocorticotropic hormone–producing pituitary adenomas after bilateral adrenalectomy

2007 ◽  
Vol 106 (6) ◽  
pp. 988-993 ◽  
Author(s):  
William J. Mauermann ◽  
Jason P. Sheehan ◽  
Daniel R. Chernavvsky ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Cranial Nerve ◽  
Adrenocorticotropic Hormone ◽  
Gamma Knife Surgery ◽  
Nelson’S Syndrome ◽  
Nelson's Syndrome ◽  
Follow Up Studies

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.

Gamma Knife surgery for invasive pituitary macroadenoma

2006 ◽  
Vol 105 (Supplement) ◽  
pp. 26-30 ◽  
Author(s):  
Mooseong Kim ◽  
Sunghwa Paeng ◽  
Seyoung Pyo ◽  
Yeonggyun Jeong ◽  
Sunil Lee ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Cavernous Sinus ◽  
Pituitary Adenomas ◽  
Gamma Knife Surgery ◽  
Tumor Control ◽  
Pituitary Macroadenoma ◽  
Female Ratio ◽  
Fractionated Radiotherapy ◽  
The Mean

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.

Gamma Knife surgery for Cushing's disease

2007 ◽  
Vol 106 (6) ◽  
pp. 980-987 ◽  
Author(s):  
Jay Jagannathan ◽  
Jason P. Sheehan ◽  
Nader Pouratian ◽  
Edward R. Laws ◽  
Ladislau Steiner ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Cranial Nerve ◽  
Gamma Knife Surgery ◽  
Cushing's Disease ◽  
Free Cortisol ◽  
Radiation Induced ◽  
The Mean

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.

scholarly journals Gamma Knife in the Treatment of Pituitary Adenomas: Results of a Single Center

2013 ◽  
Vol 40 (4) ◽  
pp. 546-552 ◽  
Author(s):  
F. A. Zeiler ◽  
M. Bigder ◽  
A. Kaufmann ◽  
P. J. McDonald ◽  
D. Fewer ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Gamma Knife Radiosurgery ◽  
Tumor Diameter ◽  
Average Dose ◽  
Complication Rates ◽  
Average Maximum ◽  
Lost To Follow Up

Abstract:Introduction:Gamma Knife (GK) radiosurgery for pituitary adenomas can offer a means of tumor and biologic control with acceptable risk and low complication rates.Methods:Retrospective review of all the patients treated at our center with GK for pituitary adenomas from Nov 2003 to June 2011.Results:We treated a total of 86 patients. Ten were lost to follow-up. Mean follow was 32.8 months. There were 21 (24.4%) growth hormone secreting adenomas (GH), 8 (9.3%) prolactinomas (PRL), 8 (9.3%) adrenocorticotropic hormone secreting (ACTH) adenomas, 2 (2.3%) follicle stimulating hormone/luteinizing hormone secreting (FSH/LH) adenomas, and 47 (54.7%) null cell pituitary adenomas that were treated. Average maximum tumor diameter and volume was 2.21cm and 5.41cm3, respectively. The average dose to the 50% isodose line was 14.2 Gy and 23.6 Gy for secreting and non-secreting adenomas respectively. Mean maximal optic nerve dose was 8.87 Gy. Local control rate was 75 of 76 (98.7%), for those with followup. Thirty-three (43.4%) patients experienced arrest of tumor growth, while 42 (55.2%) patients experienced tumor regression. Of the 39 patients with secreting pituitary tumors, 6 were lost to follow-up. Improved endocrine status occurred in 16 (50.0%), while 14 (43.8%) demonstrated stability of hormone status on continued pre-operative medical management. Permanent complications included: panhypopituitarism (4), hypothyroidism (4), hypocortisolemia (1), diabetes insipidus (1), apoplexy (1), visual field defect (2), and diplopia (1).Conclusions:Gamma Knife radiosurgery is a safe and effective means of achieving tumor growth control and endocrine remission/stability in pituitary adenomas.

scholarly journals From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum – a KIMS analysis

2009 ◽  
Vol 161 (suppl_1) ◽  
pp. S75-S83 ◽  
Author(s):  
M Klose ◽  
B Jonsson ◽  
R Abs ◽  
V Popovic ◽  
M Koltowska-Häggström ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Gh Deficiency ◽  
Dynamic Condition ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Multiple Pituitary Hormone Deficiency ◽  
Pituitary Hormone Deficiency ◽  
Gh Replacement ◽  
Baseline Characteristics

ObjectiveTo describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD.DesignObservational prospective study.MethodsBaseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 IGHD, 3006 MPHD).ResultsIGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed in 35% of IGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of IGHD into MPHD was not predicted by aetiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits were predicted by age (P<0.001) and pituitary disease duration (P<0.01).ConclusionBoth AO-IGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 years of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years after the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with IGHD, is warranted.

Aggressive Cushing disease five years after the treatment of a nonfunctional pituitary adenoma

2016 ◽  
Vol 62 (5) ◽  
pp. 77-78
Author(s):  
Minodora Betivoiu ◽  
Sorina Martin ◽  
Iulia Soare ◽  
Alexandra Nila ◽  
Simona Fica
Keyword(s):  
Pituitary Adenoma ◽  
Gamma Knife ◽  
Pituitary Adenomas ◽  
Histopathological Examination ◽  
Case Reports ◽  
Dependent Diabetes Mellitus ◽  
Ki 67 ◽  
The Right ◽  
Gamma Knife Therapy

Introduction. Cushing's disease (CD) represents 10%–12% of all pituitary adenomas and is seen predominantly in women, with a female-to-male ratio of 8:1. Although most patients with ACTH-secreting adenomas present with benign, small tumors, some have invasive macroadenomas. Rarely, nonfunctional pituitary adenomas (NFPAs) may gain secretory function, but there have been a few case reports of metamorphosis to CD.Case report. We report the case of a 59-year-old female diagnosed in 2007 with a NFPA and panhypopituitarism. She had two transsphenoidal surgeries and Gamma Knife therapy and started replacement treatment with levothyroxine 75mcg/day and prednisone 5mg/day. The postoperative course was favorable and imagistic follow-up between 2007-2014 showed progressive reduction of the residual tumor and empty sella. From personal history we note noninsulin-dependent diabetes mellitus, postmenopausal osteoporosis treated with bisphosphonates. In January 2015 she suffered visual loss on the right eye. Pituitary MRI showed supra and parasellar tumor recurrence of 27/24/17mm, infiltrating the right side of the cavernous sinus, extending around the right internal carotid artery and optic nerve, compressing the optic chiasm. In March 2015 a third transsphenoidal partial excision of the tumor was performed and in August Gamma Knife therapy was repeated. The histopathological examination was consistent with a pituitary adenoma but immunohistochemical staining for ACTH was positive, with Ki-67=25%. She had no non-specific cushingoid features. Laboratory test: glucose=116mg/dl, HbA1c=7.5%, FSH=3.34mIU/ml, LH=0.585mIU/ml TSH=0.044mcIU/ml, FT4=1.13ng/dl. Prednisone replacement therapy was stopped and CD was confirmed: 8AMcortisol=13.3mcg/dl, 23PMcortisol=11.3mcg/dl, ACTH=70.2pg/ml, 8AMcortisol after 1mg dexamethasone overnight=13.8mcg/dl. Ophthalmic exam: blindness in the right eye, slightly decreased visual field in the left eye. Pituitary MRI 8-month postsurgery revealed a 28/31/28mm invasive tumor. We started treatment with Cabergoline 3mg/week and recommended closely biological and imagistic follow-up, hoping for a good response to radiotherapy.Conclusions: Our case stresses the importance of regular, lifelong follow-up of patients with NFPAs. Chiloiro et al have reported that pituitary adenomas with Ki-67≥1.5% have a higher risk of recurrence. Although the characteristics of patients with CD have been well known for decades, the diagnosis and management of this disease are often challenging.

scholarly journals Phenotypic Variability in Familial Combined Pituitary Hormone Deficiency Caused by a PROP1 Gene Mutation Resulting in the Substitution of Arg→Cys at Codon 120 (R120C)1

1998 ◽  
Vol 83 (10) ◽  
pp. 3727-3734 ◽  
Author(s):  
Christa Flück ◽  
Johnny Deladoey ◽  
Kuno Rutishauser ◽  
Andrée Eblé ◽  
ULRICH Marti ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Failure To Thrive ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Ames Dwarf ◽  
Hypothalamic Pituitary Axis ◽  
Prop1 Gene

As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). A mutation in a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df) mouse phenotype, and thereafter, different PROP1 gene alterations have been found in humans with CPHD. We report on the follow-up of two consanguineous families (n = 12), with five subjects affected with CPHD (three males and two females) caused by the same nucleotide C to T transition, resulting in the substitution of Arg→Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype, even among patients with the same mutation. The age at diagnosis was dependent on the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient TSH deficiency was the first symptom of the disorder, all patients became symptomatic by exhibiting severe growth retardation and failure to thrive, which was mainly caused by GH deficiency (n = 4). The secretion of the pituitary-derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All of the subjects entered puberty spontaneously, and the two females also experienced menarche and periods before a replacement therapy was necessary.

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