Factors Associated With Endocrine Deficits After Stereotactic Radiosurgery of Pituitary Adenomas

Abstract OBJECTIVE To analyze the factors associated with anterior pituitary deficits after pituitary adenoma stereotactic radiosurgery (SRS). METHODS The tumor, pituitary stalk, and pituitary gland were segmented on the dose plans of 82 patients (secreting tumors, n = 53; nonsecreting tumors, n = 29) for dose-volume analysis. No patient had undergone prior radiation therapy and all patients had at least 12 months of endocrinological follow-up (median, 63 months; mean, 69 months; range, 13–134). RESULTS Thirty-four patients (41%) developed new anterior pituitary deficits at a median of 32 months (range, 2–118) after SRS. The risk of developing new anterior pituitary deficits was 16% and 45% at 2 and 5 years, respectively. Multivariate analysis of the entire group showed that poor visualization of the pituitary gland (hazard ratio [HR] = 2.63, 95% confidence interval [CI] = 1.10–6.25, P = .03) was associated with a higher rate of new anterior pituitary deficits. Dosimetric analysis of 60 patients whose pituitary gland could be clearly identified showed that increasing mean pituitary gland radiation dose correlated with new anterior pituitary deficits (HR = 1.11, 95% CI = 1.02–1.20, P = .02). New anterior pituitary deficits stratified by mean pituitary gland radiation dose: ≤7.5 Gy, 0% (0/7); 7.6 to 13.2 Gy, 29% (7/24); 13.3 to 19.1 Gy, 39% (9/23); >19.1 Gy, 83% (5/6). CONCLUSION New endocrine deficits after pituitary adenoma radiosurgery were correlated with increasing radiation dose to the pituitary gland. Methods that limit the radiation dose to the pituitary gland during SRS may increase the probability of preserving pituitary function.

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Hypopituitarism After Stereotactic Radiosurgery for Pituitary Adenomas

Neurosurgery ◽

10.1227/neu.0b013e3182846e44 ◽

2012 ◽

Vol 72 (4) ◽

pp. 630-637 ◽

Cited By ~ 66

Author(s):

Zhiyuan Xu ◽

Mary Lee Vance ◽

David Schlesinger ◽

Jason P. Sheehan

Keyword(s):

Pituitary Adenoma ◽

Radiation Dose ◽

Stereotactic Radiosurgery ◽

Tumor Control ◽

Increased Risk ◽

Free Cortisol ◽

Suprasellar Extension ◽

New Onset ◽

Stimulating Hormone

Abstract BACKGROUND: Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. OBJECTIVE: We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. METHODS: This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately before SRS and in regular follow-ups. Assessment consisted of 24-hour urine free cortisol (patients with Cushing disease), serum adrenocorticotropic hormone, cortisol, follicle-stimulating hormone, luteinizing hormone, insulin-like growth factor-1, growth hormone, testosterone (men), prolactin, thyroid-stimulating hormone, and free T4. RESULTS: Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least 1 axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based on endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years after SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior radiation therapy, and age at SRS. CONCLUSION: SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were 2 independent predictors of SRS-induced hypopituitarism.

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Effect of Distance from Target on Hypopituitarism After Stereotactic Radiosurgery for Pituitary Adenomas

10.21203/rs.3.rs-1037768/v1 ◽

2021 ◽

Author(s):

Natasha Ironside ◽

Harrison Snyder ◽

Zhiyuan Xu ◽

David Schlesinger ◽

Ching-Jen Chen ◽

...

Keyword(s):

Pituitary Gland ◽

Stereotactic Radiosurgery ◽

Predictive Value ◽

Pituitary Adenomas ◽

Anterior Pituitary ◽

Pituitary Function ◽

Anterior Pituitary Function ◽

Function Preservation ◽

Hypothalamic Pituitary Axis

Abstract IntroductionDelayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. The aim of this study was to investigate the relationship between the distance from the hypothalamic-pituitary axis to the treatment target and anterior pituitary function preservation after SRS. MethodsBetween 2007 and 2020, consecutive adult patients who underwent single-session SRS for pituitary adenomas with ³6 months of follow-up were included. Distance measurements between hypothalamic-pituitary axis structures and the SRS target volume were quantified on MRI. The primary outcome was anterior pituitary function preservation. Outcomes were compared using multivariable regression and area under the receiver operator characteristic curve (AUROC) analyses. ResultsThe study cohort comprised 224 patients, who were categorized by preservation (n=168) and no preservation (n=56) of anterior pituitary function after SRS. Independent predictors of anterior pituitary function preservation were a greater distance between the center of the pituitary gland and center of the SRS target (OR=1.101 [1.000–1.213], p=0.050), and a shorter clinical follow-up duration (OR=0.985 [0.977–0.993], p<0.0001). The adjusted AUROC for the distance from the center of the pituitary gland and center of the SRS target in predicting anterior pituitary function preservation was 0.595. The sensitivity, specificity, positive predictive value and negative predictive value in predicting anterior pituitary function preservation at the optimal cut-off distance of 15mm were 30.0%, 88.0%, 89.9% and 26.2%, respectively.ConclusionsGreater distance between the normal pituitary gland and the SRS target is associated with anterior pituitary function preservation and increasing this distance should be a goal of adenoma resection. Larger prospective, multi-center studies are necessary to corroborate this finding and establish the effects of distance on hypopituitarism after SRS for pituitary adenomas.

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An unrecognized endocrinology emergency masquerading as a hypertensive emergency: A can’t miss diagnosis

Case Reports in Internal Medicine ◽

10.5430/crim.v4n1p21 ◽

2016 ◽

Vol 4 (1) ◽

pp. 21

Author(s):

Yanerys Agosto Vargas ◽

Sharon Velez Maymi ◽

Paola Mansilla Letelier ◽

Luis Raul Hernandez-Vazquez ◽

Samayra Miranda Rodriguez ◽

...

Keyword(s):

Risk Factors ◽

Pituitary Adenoma ◽

Mortality Rate ◽

Pituitary Gland ◽

Pituitary Apoplexy ◽

Systemic Hypertension ◽

Pituitary Macroadenoma ◽

Rare Entity ◽

Factors Associated ◽

Multiple Risk Factors

Pituitary apoplexy secondary to sellar tumors is a rare entity that carries a high mortality rate. It could be secondary to infarction or hemorrhage of the pituitary gland. The incidence remains unclear, most are reported in men between the ages of 50 to 60. In the majority of times, apoplexy is idiopathic in nature, without a clear discernible cause. However, there are multiple risk factors associated with this entity, such as systemic hypertension, among others. There are few cases of pituitary apoplexy caused by infarction of a pituitary macroadenoma. We present this case of pituitary apoplexy secondary to infarction of a nonfunctional pituitary adenoma in a young woman, with a fortunate resolution.

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CMET-41. OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY (SRS) FOR LIMITED BRAIN METASTASES - AN AUSTRALIAN SINGLE INSTITUTIONAL EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noz175.242 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi60-vi60

Author(s):

Lilly Shen ◽

Wee Loon Ong ◽

Briana Farrugia ◽

Anna Seeley ◽

Carlos Augusto Gonzalvo ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Cumulative Incidence ◽

Multivariate Analyses ◽

Primary Lung Cancer ◽

Factors Associated ◽

Distant Failure ◽

Kaplan Meier ◽

Institutional Experience

Abstract INTRODUCTION Despite increasing use of stereotactic radiosurgery (SRS) for management of brain metastases (BM), published Australian data is scarce. We aim to report on the outcomes following SRS for limited BM in a single Australian institution. METHODS This is a retrospective cohort of patients with limited BM treated with SRS between August 2015 and March 2019. A dose of 24Gy/3# were prescribed to intact lesion, and 21Gy/3# to surgical cavity post-surgical resection. All patients were followed with 3-monthly surveillance MRI brain. Primary outcomes were: local failure (LF: increased in size of SRS-treated BM lesion/ recurrence in surgical cavity), distant failure (DF: intracranial progression outside of the SRS-treated lesion/ cavity), and overall survival (OS). LF, DF and OS were estimated using the Kaplan-Meier method. Multivariate Cox regressions were used to evaluate factors associated with outcomes of interest, with death as competing-risk events for LF and DF. RESULTS 76 courses of SRS were delivered in 65 patients (54 unresected BM lesions, and 22 surgical cavities). 43 (66%) patients were ECOG 0–1. 35 (54%) patients had solitary BM. 41 (63%) had symptomatic BM. Half of the patients had primary lung cancer. Median follow-up was 4.8 months (range:0.1–39 months). 10 LF were observed at a median of 3.5 month post-SRS, with 6- and 12-month LF cumulative incidence of 14% and 24% respectively. 30 DF were observed at a median of 3.3 months, with 6- and 12-month DF cumulative incidence of 38% and 63% respectively. The 12- and 24-month OS were 39% and 26% respectively. In multivariate analyses, better ECOG status, solitary BM lesion, resection of BM pre-SRS, and use of subsequent systemic therapy were independently associated with improved OS. CONCLUSION This is one of the few Australian series reporting on outcomes following SRS for limited BM, with comparable outcomes to published international series.

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Radiosurgical Management of Benign Cavernous Sinus Tumors: Dose Profiles and Acute Complications

Neurosurgery ◽

10.1097/00006123-200105000-00011 ◽

2001 ◽

Vol 48 (5) ◽

pp. 1022-1032 ◽

Cited By ~ 33

Author(s):

Joseph C.T. Chen ◽

Steven L. Giannotta ◽

Cheng Yu ◽

Zbigniew Petrovich ◽

Michael L. Levy ◽

...

Keyword(s):

Surgical Treatment ◽

Pituitary Adenoma ◽

Radiation Dose ◽

Cavernous Sinus ◽

Cranial Nerve ◽

Cranial Nerve Palsy ◽

Nerve Palsy ◽

Tumor Volume ◽

Grade Iii

Abstract OBJECTIVE Radiosurgery has emerged as an alternative treatment modality for cranial base tumors in patients deemed not suited for primary surgical extirpation, patients with recurrent or residual tumor after open surgery, or patients who refuse surgical treatment. We review our short-term experience with radiosurgical management of cavernous sinus region tumors with the Leksell gamma knife. METHODS From August 1994 to February 1999, 69 patients with cavernous sinus lesions were treated in 72 separate treatment sessions. The tumor type distribution was 29 pituitary adenomas, 35 meningiomas, 4 schwannomas, and 1 paraganglioma. The median follow-up was 122 weeks. Lesions were stratified according to a five-level surgical grade. The grade distribution of the tumors was as follows: Grade I, 13; Grade II, 21; Grade III, 19; Grade IV, 12; Grade V, 4. Median tumor volume was 4.7 cm3. The median radiation dose was 15 Gy to the 50% isodose line. Median maximal radiation dose was 30 Gy. RESULTS Analysis of tumor characteristics and radiation dose to optic nerve and pontine structures revealed a significant correlation between distance and dose. Much lower correlation coefficients were found between tumor volume and dose. One lesion in this series had evidence of transient progression and later regression on follow-up radiographic studies. No other lesions in this series were demonstrated to have exhibited progression. Complications after radiosurgical treatment were uncommon. Two patients had cranial nerve deficits after treatment. One patient with a surgical Grade III pituitary adenoma had VIth cranial nerve palsy 25 months after radiosurgical treatment that spontaneously resolved 10 months later. A patient with a bilateral pituitary adenoma experienced bilateral VIth cranial nerve palsy 3 months after treatment that had not resolved at 35 months after treatment. Six patients with preoperative cranial nerve deficits experienced resolution or improvement of their deficits after treatment. One patient with a prolactin-secreting adenoma experienced normalization of endocrine function with return of menses. CONCLUSION Radiosurgical treatment represents an important advance in the management of cavernous sinus tumors, with low risk of neurological deficit in comparison with open surgical treatment, even in patients with high surgical grades.

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Abstract TP490: Long Term Clinical Results of Linear Accelerator Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Single Institution Experience of 18 Years

Stroke ◽

10.1161/str.51.suppl_1.tp490 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yung Ki Park ◽

Hae-Won Koo

Keyword(s):

Adverse Event ◽

Radiation Dose ◽

Stereotactic Radiosurgery ◽

Linear Accelerator ◽

Clinical Results ◽

Single Institution ◽

High Radiation ◽

Cerebral Avms

Introduction: Cerebral arteriovenous malformation (AVM) is an intracranial pial vascular lesion which is treated with microsurgery, endovascular treatment or stereotactic radiosurgery (SRS). We introduce the long-term clinical results of linear accelerator (LINAC) stereotactic radiosurgery for cerebral AVM which is treated in single institution for 18 years period. Methods: Retrospective chart review was held in cerebral AVM patients treated with Novalis (BrainLAB AG, Heimstetten, Germany) stereotactic radiotherapy from 2001 to 2018. Clinical results such as obliteration rate, hemorrhage rate after SRS, and radiosurgery related adverse event was analyzed. Furthermore, predictors for obliteration and symptomatic radiosurgery induced adverse event was analyzed with multivariate logistic regression test. Results: Among 117 patients with cerebral AVMs treated with LINAC-based SRS, 72 were included in study. Total obliteration rate was 80.6% (58/72) for mean 57.0±48.3 months follow up period. Post-SRS hemorrhage and mortality rate was 6.9% (4/72) and 1.4% (1/72), respectively. Mean radiation dose and volume was 22.8Gy and 3.7cc, respectively. Independent predictive factors for nidus obliteration was: (1) radiation dose (OR 1.43, 95% CI 1.04-2.08, p=0.0374), (2) Ruptured AVM (OR 12.18, 95% CI 2.38-86.47, p=0.0054), (3) Virginia AVM score (OR 0.21, 95% CI 0.07-0.53, p=0.0028), and (4) follow up period months (OR 1.03, 95% CI 1.01-1.06, p=0.0261). Independent risk factors for symptomatic radiosurgery related adverse event was radiation volume (OR 1.61, 95% CI 1.09-2.65, p=0.0326). Conclusion: LINAC-based SRS is effective and relatively safe method for treatment of cerebral AVMs. Independent predictive factors for obliteration was high radiation dosage, ruptured status, low Virginia AVM score, and long follow up period. High radiation volume was related to symptomatic radiation induced adverse event.

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Anterior Pituitary Function in Patients with Nonfunctioning Pituitary Adenoma: Results of Longitudinal Follow-up.

Endocrine Journal ◽

10.1507/endocrj.42.421 ◽

1995 ◽

Vol 42 (3) ◽

pp. 421-427 ◽

Cited By ~ 24

Author(s):

ATSUSHI TOMINAGA ◽

TOHRU UOZUMI ◽

KAZUNORI ARITA ◽

KAORU KURISU ◽

TAKASHI YANO ◽

...

Keyword(s):

Pituitary Adenoma ◽

Anterior Pituitary ◽

Pituitary Function ◽

Nonfunctioning Pituitary Adenoma ◽

Anterior Pituitary Function

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Negative surgical exploration in patients with Cushing’s disease: benefit of two-thirds gland resection on remission rate and a review of the literature

Journal of Neurosurgery ◽

10.3171/2017.5.jns162901 ◽

2018 ◽

Vol 129 (5) ◽

pp. 1260-1267 ◽

Cited By ~ 3

Author(s):

Steven B. Carr ◽

Bette K. Kleinschmidt-DeMasters ◽

Janice M. Kerr ◽

Katja Kiseljak-Vassiliades ◽

Margaret E. Wierman ◽

...

Keyword(s):

Pituitary Gland ◽

Cushing’S Disease ◽

Remission Rate ◽

Cushing's Disease ◽

Entire Group ◽

Cell Hyperplasia ◽

Cell Adenoma ◽

Surgical Exploration ◽

Acth Cell

OBJECTIVEThe authors report their single-institution experience with the pathological findings, rates of remission, and complications in patients with presumed Cushing’s disease (CD) who underwent a two-thirds pituitary gland resection when no adenoma was identified at the time of transsphenoidal surgery (TSS). The authors also review the literature on patients with CD, negative surgical exploration, and histological findings.METHODSThis study is a retrospective analysis of cases found in neurosurgery and pathology department databases between 1989 and 2011. In all cases, patients had been operated on by the same neurosurgeon (K.O.L.). Twenty-two (13.6%) of 161 patients who underwent TSS for CD had no adenoma identified intraoperatively after systematic exploration of the entire gland; these patients all underwent a two-thirds pituitary gland resection. A chart review was performed to assess treatment data points as well as clinical and biochemical remission status.RESULTSOf the 22 patients who underwent two-thirds gland resection, 6 (27.3%) ultimately had lesions found on final pathology. All 6 patients were found to have a distinct adrenocorticotropic hormone (ACTH) cell adenoma. Sixteen (72.7%) of the patients had no tumor identified, with 3 of these patients suspected of having ACTH cell hyperplasia. The follow-up duration for the entire group was between 14 and 315 months (mean 98.9 months, median 77 months). Remission rates were 100% (6/6 patients) for the ACTH cell adenoma group and 75% (12/16) for the group without adenoma. Overall, 18 (81.8%) of the 22 patients had no evidence of hypercortisolism at last follow-up, and 4 patients (18%) had persistent hypercortisolism, defined as a postoperative cortisol level > 5 μg/dl. Of these 4 patients, 1 was suspected of harboring a cavernous sinus adenoma, 2 were found to have lung tumors secreting ACTH, and 1 remained with an undiagnosed etiology. Rates of postoperative complications were low.CONCLUSIONSThe diagnosis and treatment of CD can be challenging for neurosurgeons, endocrinologists, and pathologists alike. Failure to find a discrete adenoma at the time of surgery occurs in at least 10%–15% of cases, even in experienced centers. The current literature provides little guidance regarding rational intraoperative approaches in such cases. The authors’ experience with 161 patients with CD, when no intraoperative tumor was localized, demonstrates the utility of a two-thirds pituitary gland resection with a novel and effective surgical strategy, as suggested by a high initial remission rate and a low operative morbidity.

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Endocrinological outcome after pituitary transposition (hypophysopexy) and adjuvant radiotherapy for tumors involving the cavernous sinus

Journal of Neurosurgery ◽

10.3171/2011.2.jns10566 ◽

2011 ◽

Vol 115 (1) ◽

pp. 55-62 ◽

Cited By ~ 22

Author(s):

Philipp Taussky ◽

Ricky Kalra ◽

Jeroen Coppens ◽

Jahan Mohebali ◽

Randy Jensen ◽

...

Keyword(s):

Pituitary Gland ◽

Stereotactic Radiosurgery ◽

Cavernous Sinus ◽

Stereotactic Radiotherapy ◽

Pituitary Adenomas ◽

Residual Tumor ◽

Fractionated Stereotactic Radiotherapy ◽

Normal Pituitary Gland ◽

Radiotherapy Treatment

Object Stereotactic radiosurgery and fractionated stereotactic radiotherapy are commonly used in the treatment of residual or recurrent benign tumors of the skull base and cavernous sinus. A major risk associated with radiosurgical or radiotherapy treatment of residual or recurrent tumors adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors have used a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual tumor within the cavernous sinus. Here, the authors analyze the long-term endocrinological outcomes in patients with residual and recurrent tumors who undergo hypophysopexy and adjuvant radiosurgical or conformal fractionated radiotherapy treatment. Methods Pituitary transposition involves placement of a fat graft between the normal pituitary gland and residual tumor in the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and the graft is interposed between the pituitary gland and the residual tumor. The residual tumor may then be treated with stereotactic radiosurgery or conformal fractionated radiation therapy. The authors evaluated endocrinological outcome, safety of the procedure, and postoperative complications in patients who underwent this procedure during a 7-year period. Results Hypophysopexy has been used in 34 patients with nonfunctioning pituitary adenomas (19), functional pituitary adenomas (8), chordomas (2), meningiomas (2), chondrosarcoma (1), hemangiopericytoma (1), or hemangioma (1) involving the sella and cavernous sinus. Follow-up (radiographic and endocrinological) has been performed yearly in all patients. Two patients experienced postoperative endocrine deficits before radiosurgery (1 transient), but none of the patients developed new hypopituitarism during the median 4-year follow-up (range 1–8 years) after radiosurgery or fractionated stereotactic radiotherapy. Conclusions The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery or radiotherapy and effectively reduces the incidence of radiation injury to the normal pituitary gland when compared with historical controls.

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Endocrine Outcomes In Central Diabetes Insipidus: the Predictive Value of Neuroimaging “Mismatch Pattern”

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa540 ◽

2020 ◽

Vol 105 (11) ◽

Author(s):

Deborah Bianco ◽

Flavia Napoli ◽

Giovanni Morana ◽

Angela Pistorio ◽

Anna Elsa Maria Allegri ◽

...

Keyword(s):

Pituitary Gland ◽

Diabetes Insipidus ◽

Contrast Enhancement ◽

Anterior Pituitary ◽

Magnetic Resonance Images ◽

Central Diabetes Insipidus ◽

Pituitary Hormone ◽

Gland Size ◽

Pituitary Dysfunction

Abstract Context The etiology of central diabetes insipidus (CDI) in children is often unknown. Clinical and radiological features at disease onset do not allow discrimination between idiopathic forms and other conditions or to predict anterior pituitary dysfunction. Objective To evaluate the evolution of pituitary stalk (PS) thickening and the pattern of contrast-enhancement in relation with etiological diagnosis and pituitary function. Methods We enrolled 39 children with CDI, 29 idiopathic and 10 with Langerhans cell histiocytosis (LCH). Brain magnetic resonance images taken at admission and during follow-up (332 studies) were examined, focusing on PS thickness, contrast-enhancement pattern, and pituitary gland size; T2-DRIVE and postcontrast T1-weighted images were analyzed. Results Seventeen of 29 patients (58.6%) with idiopathic CDI displayed “mismatch pattern,” consisting in a discrepancy between PS thickness in T2-DRIVE and postcontrast T1-weighted images; neuroimaging findings became stable after its appearance, while “mismatch” appeared in LCH patients after chemotherapy. Patients with larger PS displayed mismatch more frequently (P = 0.003); in these patients, reduction of proximal and middle PS size was documented over time (P = 0.045 and P = 0.006). The pituitary gland was smaller in patients with mismatch (P < 0.0001). Patients with mismatch presented more frequently with at least one pituitary hormone defect, more often growth hormone deficiency (P = 0.033). Conclusions The PS mismatch pattern characterizes patients with CDI, reduced pituitary gland size, and anterior pituitary dysfunction. The association of mismatch pattern with specific underlying conditions needs further investigation. As patients with mismatch show stabilization of PS size, we assume a prognostic role of this peculiar pattern, which could be used to lead follow-up.

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