Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion

Background: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly. Methods: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible. Results: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism. Conclusions: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission.

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MON-298 IGF-1 in the Early Post-operative Assessment of Acromegaly

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.287 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Diane Donegan ◽

Alicia Algeciras-Schimnich ◽

Dana Z Erickson

Keyword(s):

Cavernous Sinus ◽

Surgical Intervention ◽

Patient Anxiety ◽

Cavernous Sinus Invasion ◽

Delayed Treatment ◽

First Line Therapy ◽

Significant Difference ◽

Suppression Test ◽

Operative Assessment

Abstract Introduction: Transsphenoidal surgery is recommended as first line therapy in the vast majority of patients with acromegaly. Successful surgical intervention is determined by normalization of insulin like-growth factor (IGF) - 1 and adequate suppression of growth hormone (GH) during glucose GH suppression test or random GH levels <1.0 ng/mL. Given the long half-life of IGF-1, evolution of IGF-1 and GH assays and limitations of GH suppression test, clinicians remain reliant on IGF-1 results 3–6 months following surgery to assess disease remission following surgical intervention. This can lead to delayed treatment of patients with persistent disease and significantly increase patient anxiety. Aim: To determine if IGF-1 levels at 6 weeks were equally predictive of surgical outcomes when compared to IGF-1 levels at 3–6 months postoperative. Methods: Retrospective review of patients with newly diagnosed acromegaly who had surgery between 2010–2019 and had post-operative IGF-1 level measured at 6 weeks and 3–6 months. IGF-1 was measured using the Siemens Immulite assay until 2016 when it was replaced by a LC-MS/MS assay. IGF-1 measurements at 6 weeks are obtained based on clinician discretion. Results: 69 patients (mean age 49 ± 14.8, female 31/69, 44.9%) with acromegaly had surgery and IGF-1 follow-up measurements at 6 weeks and 3–6 months. Persistent acromegaly was noted in 45/69 at 3–6 months. The median IGF-1 pre-operative was 701 ng/ mL (289–1600), 6 weeks postoperative was 286 ng/ mL (109–1038) and at 3–6 months was 267 ng/ mL (77–996). The median pre-operative IGF-1 was significantly higher than the median IGF-1 level at 6 weeks and 3–6 months (P=<0.001). Although a statistically significant difference was seen between IGF-1 levels at 6 weeks and 3–6 months, the mean difference between these time points was small (20 ng/mL, P=<0.001). There was a greater percent reduction in IGF-1 at 6 weeks following surgery in those who had a normal IGF-1 at 3–6 months compared to those who did not (63% vs 35%, P=<0.01). Among patients who were deemed in remission at 3–6 months (24/69, 35%), 3/24 patients (all male with macroadenoma and no cavernous sinus invasion) had mildly elevated IGF-1 levels at 6 weeks (≤1.12 upper limit of normal) which subsequently normalized. In all of these patients, GH was <1 ng/mL post-op. In 1 male (macroadenoma and cavernous sinus invasion), IGF-1 levels increased from normal at 6 weeks to abnormal when measured at 3–6 months. Conclusion: In the vast majority of patients, 6 weeks post-operative IGF-1 can be used to assess response to surgery avoiding a delay in treatment. However, we would recommend repeating IGF-1 levels at 3–6 months in those who have marginally elevated IGF-1 above normal (≤ 1.12), without cavernous sinus invasion and a post-operative GH of <1 ng/mL prior to intervening if the IGF-1 is elevated 6 weeks as the IGF-1 may normalize.

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Early Results of Microsurgical Treatment of Acromegaly

International Neuroscience Journal ◽

10.1515/inj-2017-0004 ◽

2018 ◽

Vol 2 (1) ◽

pp. 22-29 ◽

Cited By ~ 1

Author(s):

Pablo Ajler ◽

Alvaro Campero ◽

Federico Landriel ◽

Ezequiel Goldschmidt ◽

Santiago Hem ◽

...

Keyword(s):

Cavernous Sinus ◽

Multivariate Logistic Regression Analysis ◽

Transnasal Approach ◽

Cavernous Sinus Invasion ◽

Early Results ◽

Contrast Enhanced ◽

Major Predictor ◽

Cure Rates ◽

Disease Persistence

Abstract Purpose Acromegaly is an unusual disorder caused by abnormal oversecretion of growth hormone by pituitary adenomas. Transsphenoidal surgery is frequently the first management option. The objective of this article is to establish the effectiveness of a transnasal transsphenoidal approach in the treatment of GH-producing adenomas, and to identify risk factors for disease persistence. Methods We conducted a retrospective review of 81 patients treated for acromegaly with transsphenoidal microsurgery between 2006 and 2010. Results Macroadenomas accounted for 66.7% of the cases, contrast-enhanced MRI revealing cavernous sinus invasion in 28.4% of the patients (23 subjects). Cure was achieved in 72.8% (59 of 82). All microadenomas (27 cases) were managed effectively with surgery whereas cure rates stood at 66.7% for macroadenomas. Monovariate analysis showed that disease persistence was statistically associated with three variables. Odds ratio for remission stood at 1.68 for microadenomas and 0.033 for cavernous sinus invasion (p<0.001). Preoperative GH values were statistically associated with cure during follow up (p<0.05). Multivariate logistic regression analysis showed that only cavernous sinus invasion continued to be significantly associated with disease persistence (OR 3.52, p<0.05). Conclusion The transnasal approach proves effective in the treatment and cure of acromegaly. Cavernous sinus invasion is a major predictor of disease persistence.

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The outcomes of conservatively observed asymptomatic nonfunctioning pituitary adenomas with optic nerve compression

Journal of Neurosurgery ◽

10.3171/2020.4.jns192778 ◽

2020 ◽

pp. 1-8

Author(s):

Kihwan Hwang ◽

Yong Hwy Kim ◽

Jung Hee Kim ◽

Jung Hyun Lee ◽

Hee Kyung Yang ◽

...

Keyword(s):

Optic Nerve ◽

Natural History ◽

Cavernous Sinus ◽

Pituitary Adenomas ◽

Nerve Compression ◽

Cavernous Sinus Invasion ◽

Nonfunctioning Pituitary Adenomas ◽

History Of ◽

Optic Nerve Compression

OBJECTIVEThe authors investigated the natural history of asymptomatic nonfunctioning pituitary adenomas (NFPAs) with optic nerve compression.METHODSThis study retrospectively analyzed the natural history of asymptomatic NFPAs with documented optic nerve compression on MRI diagnosed between 2000 and 2016 from 2 institutions. The patients were followed up with regular endocrinological, ophthalmological, and radiological evaluations, and the endpoint was new endocrinopathy or neurological deficits.RESULTSThe study comprised 81 patients. The median age at diagnosis was 58.0 years and the follow-up duration was 60.0 months. As the denominator of overall pituitary patients, 2604 patients were treated with surgery after diagnosis at the 2 institutions during the same period. The mean initial and last measured values for tumor diameter were 23.7 ± 8.9 mm and 26.2 ± 11.4 mm, respectively (mean ± SD). Tumor growth was observed in 51 (63.0%) patients; however, visual deterioration was observed in 14 (17.3%) patients. Ten (12.3%) patients experienced endocrine deterioration. Fourteen (17.3%) patients underwent surgery for either visual deterioration (in 12 patients) or endocrine dysfunction (in 2 patients). After surgery, all patients experienced improvements in visual or hormonal function. The actuarial rates of treatment-free survival at 2, 3, and 5 years were 96.1%, 93.2%, and 85.6%, respectively. In the multivariate analysis, initial cavernous sinus invasion (HR 4.985, 95% CI 1.597–15.56; p = 0.006) was the only independent risk factor for eventual treatment.CONCLUSIONSThe neuroendocrinological deteriorations were not frequent and could be recovered by surgery with early detection on regular follow-up in asymptomatic NFPAs with documented optic nerve compression on MRI. Therefore, conservative management could be an acceptable strategy for these tumors. Careful follow-up is required for tumors with cavernous sinus invasion.

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Petroclival meningiomas: surgical experience in 109 cases

Journal of Neurosurgery ◽

10.3171/jns.1996.84.1.0020 ◽

1996 ◽

Vol 84 (1) ◽

pp. 20-28 ◽

Cited By ~ 206

Author(s):

William T. Couldwell ◽

Takanori Fukushima ◽

Steven L. Giannotta ◽

Martin H. Weiss

Keyword(s):

Cavernous Sinus ◽

Surgical Approaches ◽

Surgical Removal ◽

Total Removal ◽

Content Type ◽

Cavernous Sinus Invasion ◽

Petroclival Meningiomas ◽

High Incidence ◽

Progression Of Disease

✓ The surgical removal of petroclival meningiomas has historically been associated with a high incidence of morbidity and mortality. The 109 consecutive patients included in the present retrospective study represent a combined series of tumors operated on by the four authors during a period from 1980 to 1992. The series is composed of 40 men and 69 women ranging in age from 25 to 75 years (mean 51 years). Surgical approaches to tumors in this series included simple retromastoid (60 cases), combined supra- and infratentorial petrosal (22), transtemporal (primary transsigmoid retrolabyrinthine, translabyrinthine, or transcochlear (12)), subtemporal (11), and frontotemporal transcavernous (eight). Gross-total removal was achieved in 75 patients (69%). Recurrence or progression of disease occurred in 14 patients (13%) over a 6.1-year mean follow-up period, and it was found within the cavernous sinus in 12 of these cases. Four recurrent cases demonstrated histological compatibility with malignant meningioma. Perioperative death occurred in four patients, and there were 56 significant complications in 35 other patients. Review of this series, with the attendant complications, has facilitated the authors' decision-making when considering the risk of gross-total removal in selected patients with asymptomatic cavernous sinus invasion or tumor adherent to the brainstem.

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Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

Journal of Neurosurgery ◽

10.3171/jns/2008/108/4/0736 ◽

2008 ◽

Vol 108 (4) ◽

pp. 736-745 ◽

Cited By ~ 87

Author(s):

Edward F. Chang ◽

Gabriel Zada ◽

Sang Kim ◽

Kathleen R. Lamborn ◽

Alfredo Quinones-Hinojosa ◽

...

Keyword(s):

Overall Survival ◽

Cavernous Sinus ◽

Pituitary Adenomas ◽

Rank Test ◽

Tumor Control ◽

Cavernous Sinus Invasion ◽

Log Rank Test ◽

Nonfunctional Pituitary Adenomas

Object Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. Methods The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. Results Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4–14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. Conclusions Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

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Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors

Neurosurgery ◽

10.1093/neuros/nyx020 ◽

2017 ◽

Vol 81 (2) ◽

pp. 357-366 ◽

Cited By ~ 22

Author(s):

Harish Babu ◽

Alicia Ortega ◽

Miriam Nuno ◽

Aaron Dehghan ◽

Aaron Schweitzer ◽

...

Keyword(s):

Cavernous Sinus ◽

Transsphenoidal Surgery ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Endoscopic Transsphenoidal Surgery ◽

Cavernous Sinus Invasion ◽

Remission Rates

Abstract BACKGROUND: Long-term remission rates from endoscopic transsphenoidal surgery for acromegaly and their relationship to prognostic indicators of disease aggressiveness are not well documented. OBJECTIVE: To investigate long-term remission rates in patients with acromegaly after endoscopic transsphenoidal surgery, and correlate this with molecular and radiographic markers of disease aggressiveness. METHODS: We identified all patients undergoing endoscopic transsphenoidal surgery for acromegaly from 2005 to 2013 at Cedars-Sinai Pituitary Center. Hormonal remission was established by normal insulin-like growth factor (IGF)-1, basal serum growth hormone <2.5 ng/mL, and growth hormone suppression to <1 ng/mL following oral glucose tolerance test. Oral glucose tolerance test was performed at 3 months after surgery, and then as indicated. IGF-1 was measured at 3 months and then at least annually. We evaluated tumor granularity, nuclear expression of p21, Ki67 index, and extent of cavernous sinus invasion, and correlated these with remission status. RESULTS: Fifty-eight patients that underwent surgery had follow-up from 38 to 98 months (mean 64 ± 32.2 months). There were 21 microadenomas and 37 macroadenomas. Three months after surgery 40 of 58 patients (69%) were in biochemical remission. Four additional patients were in remission at 6 months after surgery, and 1 patient had recurrence within the first year after surgery. At last follow-up, 43 of 44 (74.1%) of patients remained in remission. Cavernous sinus invasion by tumor predicted failure to achieve remission. CONCLUSIONS: Prognostic markers of disease aggressiveness other than cavernous sinus invasion did not correlate with surgical outcome. Long-term remission after surgery alone was achieved in 74% of patients, indicating long-term efficacy of endoscopic surgery.

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Long term follow-up of growth hormone-secreting pituitary adenomas submitted to endoscopic endonasal surgery

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20170035 ◽

2017 ◽

Vol 75 (5) ◽

pp. 301-306 ◽

Cited By ~ 6

Author(s):

Caroline Martins dos Santos Leopoldo ◽

Felippe Martins dos Santos Leopoldo ◽

Américo Rubens Leite dos Santos ◽

José Carlos Esteves Veiga ◽

José Viana Lima Junior ◽

...

Keyword(s):

Growth Hormone ◽

Cavernous Sinus ◽

Remission Rate ◽

Effective Technique ◽

Endoscopic Transsphenoidal Surgery ◽

Endoscopic Endonasal ◽

Cavernous Sinus Invasion ◽

Long Term Follow Up

ABSTRACT Objective The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. Methods A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. Results The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease control. The most common complication was diabetes insipidus and the most severe was an ischemic stroke. Conclusion The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.

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