Postoperative GH and Degree of Reduction in IGF-1 Predicts Postoperative Hormonal Remission in Acromegaly

PurposeDetermine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas.MethodsWe identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values.ResultsPatients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity).ConclusionPOD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.

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Endoscopic endonasal transsphenoidal approach for pituitary adenomas: technical aspects and report of casuistic

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2010000400024 ◽

2010 ◽

Vol 68 (4) ◽

pp. 608-612 ◽

Cited By ~ 16

Author(s):

Américo Rubens Leite dos Santos ◽

Roberto Monteiro Fonseca Neto ◽

José Carlos Esteves Veiga ◽

José Viana Jr ◽

Nilza Maria Scaliassi ◽

...

Keyword(s):

Pituitary Adenomas ◽

Pituitary Tumors ◽

Hormonal Control ◽

Subtotal Resection ◽

Endoscopic Endonasal ◽

Technical Aspects ◽

Transphenoidal Approach ◽

Acth Secreting ◽

Csf Leaks

OBJECTIVE: Analyse technical aspects, effectiveness and morbidity of the endoscopic endonasal transphenoidal approach for pituitary adenomas. METHOD: From January 2005 to September 2008, 30 consecutive patients underwent endoscopic endonasal resection of pituitary adenomas with a follow up from 3 to 36 months. Their medical charts were retrospectively analysed. RESULTS: There were 18 women and 12 men, mean age 44 years (range 17-65 yr). Among the 30 patients, 23 had macroadenomas and 7 microadenomas. Twelve patients had non-functioning tumors, 9 had ACTH-secreting tumors, 8 had GH-secreting tumors and 1 prolactinoma. Complete resection and hormonal control was achieved in all microadenomas. Macroadenomas were completely removed in 6 patients, subtotal resection in 6 and partial resection in 11. Three patients had diabetes insipidus and 5 had CSF leaks treated with lumbar drainage. CONCLUSION: The endonasal endoscopic approach for pituitary tumors is effective and has low morbidity.

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Cavernous Sinus Involvement by Pituitary Adenomas: Clinical Implications and Outcomes of Endoscopic Endonasal Resection

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0036-1598022 ◽

2017 ◽

Vol 38 (03) ◽

pp. 273-282 ◽

Cited By ~ 9

Author(s):

Abdulrazag Ajlan ◽

Achal Achrol ◽

Abdullah Feroze ◽

Erick Westbroek ◽

Peter Hwang ◽

...

Keyword(s):

Cavernous Sinus ◽

Pituitary Adenomas ◽

Surgical Complication ◽

Treatment Algorithm ◽

Additional Treatment ◽

Long Term Outcomes ◽

Endoscopic Endonasal ◽

Surgical Strategies

Background Parasellar invasion of pituitary adenomas (PAs) into the cavernous sinus (CS) is common. The management of the CS component of PA remains controversial. Objective The objective of this study was to analyze CS involvement in PA treated with endoscopic endonasal approaches, including incidence, surgical risks, surgical strategies, long-term outcomes, and our treatment algorithm. Methods We reviewed a series of 176 surgically treated PA with particular attention to CS involvement and whether the CS tumor was approached medial or lateral to the internal carotid artery. Results The median duration of follow-up was 36 months. Macroadenomas and nonfunctional adenomas represented 77 and 60% of cases, respectively. CS invasion was documented in 23% of cases. CS involvement was associated with a significantly diminished odds of gross total resection (47 vs. 86%, odds ratio [OR]: 5.2) and increased the need for subsequent intervention (4 vs. 40%, OR: 14.4). Hormonal remission was achieved in 15% of hormonally active tumors. Rates of surgical complication were similar regardless of CS involvement. Conclusion Our tailored strategy beginning with a medial approach and adding lateral exposure as needed resulted in good outcomes with low morbidity in nonfunctional adenomas. Functional adenomas involving the CS were associated with low rates of hormonal remission necessitating higher rates of additional treatment.

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Long-term tumor control after endoscopic endonasal resection of craniopharyngiomas: comparison of gross-total resection versus subtotal resection with radiation therapy

Journal of Neurosurgery ◽

10.3171/2021.5.jns202011 ◽

2021 ◽

pp. 1-9

Author(s):

Saniya S. Godil ◽

Umberto Tosi ◽

Mina Gerges ◽

Andrew L. A. Garton ◽

Georgiana A. Dobri ◽

...

Keyword(s):

Radiation Therapy ◽

Diabetes Insipidus ◽

Endocrine Function ◽

Gross Total Resection ◽

Tumor Control ◽

Subtotal Resection ◽

Total Resection ◽

Endoscopic Endonasal

OBJECTIVE Surgical management of craniopharyngiomas (CPAs) is challenging. Controversy exists regarding the optimal goals of surgery. The purpose of this study was to compare the long-term outcomes of patients who underwent gross-total resection with the outcomes of those who underwent subtotal resection of their CPA via an endoscopic endonasal approach. METHODS From a prospectively maintained database of all endoscopic endonasal approaches performed at Weill Cornell Medicine, only patients with CPAs with > 3 years of follow-up after surgery were included. The primary endpoint was radiographic progression. Data were collected on baseline demographics, imaging, endocrine function, visual function, and extent of resection. RESULTS A total of 44 patients with a mean follow-up of 5.7 ± 2.6 years were included. Of these patients, 14 (31.8%) had prior surgery. GTR was achieved in 77.3% (34/44) of all patients and 89.5% (34/38) of patients in whom it was the goal of surgery. Preoperative tumor volume < 10 cm3 was highly predictive of GTR (p < 0.001). Radiation therapy was administered within the first 3 months after surgery in 1 (2.9%) of 34 patients with GTR and 7 (70%) of 10 patients with STR (p < 0.001). The 5-year recurrence-free/progression-free survival rate was 75.0% after GTR and 25.0% after STR (45% in subgroup with STR plus radiotherapy; p < 0.001). The time to recurrence after GTR was 30.2 months versus 13 months after STR (5.8 months in subgroup with STR plus radiotherapy; p < 0.001). Patients with GTR had a lower rate of visual deterioration and higher rate of return to work or school compared with those with STR (p = 0.02). Patients with GTR compared to STR had a lower rate of CSF leakage (0.0% vs 30%, p = 0.001) but a higher rate of diabetes insipidus (85.3% vs 50%, p = 0.02). CONCLUSIONS GTR, which is possible to achieve in smaller tumors, resulted in improved tumor control, better visual outcome, and better functional recovery but a higher rate of diabetes insipidus compared with STR, even when the latter was supplemented with postoperative radiation therapy. GTR should be the goal of craniopharyngioma surgery, when achievable with minimal morbidity.

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Long-term outcomes after endoscopic endonasal surgery for nonfunctioning pituitary macroadenomas

Journal of Neurosurgery ◽

10.3171/2019.11.jns192457 ◽

2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Mina M. Gerges ◽

Kavelin Rumalla ◽

Saniya S. Godil ◽

Iyan Younus ◽

Walid Elshamy ◽

...

Keyword(s):

Radiation Therapy ◽

Pituitary Adenomas ◽

Tumor Volume ◽

Endoscopic Endonasal Surgery ◽

Endonasal Surgery ◽

Ki 67 ◽

Endoscopic Endonasal ◽

Pituitary Macroadenomas

OBJECTIVENonfunctioning pituitary adenomas are benign, slow-growing tumors. After gross-total resection (GTR) or subtotal resection (STR), tumors can recur or progress and may ultimately require additional intervention. A greater understanding of long-term recurrence and progression rates following complete or partial resection and the need for further intervention will help clinicians provide meaningful counsel for their patients and assist data-driven decision-making.METHODSThe authors retrospectively analyzed their institutional database for patients undergoing endoscopic endonasal surgery (EES) for nonfunctioning pituitary macroadenomas (2003–2014). Only patients with follow-up of at least 5 years after surgery were included. Tumor volumes were measured on pre- and postoperative MRI. Tumor recurrence was defined as the presence of a 0.1-cm3 tumor volume after GTR, and tumor progression was defined as a 25.0% increase in residual tumor after STR.RESULTSA total of 190 patients were included, with a mean age of 63.8 ± 13.2 years; 79 (41.6%) were female. The mean follow-up was 75.0 ± 18.0 months. GTR was achieved in 127 (66.8%) patients. In multivariate analysis, age (p = 0.04), preoperative tumor volume (p = 0.03), Knosp score (p < 0.001), and Ki-67 (p = 0.03) were significant predictors of STR. In patients with GTR, the probability of recurrence at 5 and 10 years was 3.9% and 4.7%, and the probability of requiring treatment for recurrence was 0.79% and 1.6%, respectively. In 63 patients who underwent STR, 6 (9.5%) received early postoperative radiation and did not experience progression, while the remaining 57 (90.5%) were observed. Of these, the probability of disease progression at 5 and 10 years was 21% and 24.5%, respectively, and the probability of requiring additional treatment for progression was 17.5% and 21%. Predictors of recurrence or progression in the entire group were Knosp score (p < 0.001) and elevated Ki-67 (p = 0.03). Significant predictors of progression after STR in those who did not receive early radiotherapy were cavernous sinus location (p < 0.05) and tumor size > 1.0 cm3 (p = 0.005).CONCLUSIONSFollowing GTR for nonfunctioning pituitary adenomas, the 10-year chance of recurrence is low and the need for treatment even lower. After STR, although upfront radiation therapy may prevent progression, even without radiotherapy, the need for intervention at 10 years is only approximately 20% and a period of observation may be warranted to prevent unnecessary prophylactic radiation therapy. Tumor volume > 1 cm3, Knosp score ≥ 3, and Ki-67 ≥ 3% may be useful metrics to prompt closer follow-up or justify early prophylactic radiation therapy.

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Comparative preoperative characteristics and postoperative outcomes at a private versus a safety-net hospital following endoscopic endonasal transsphenoidal resection of pituitary adenomas

Journal of Neurosurgery ◽

10.3171/2019.12.jns192506 ◽

2020 ◽

pp. 1-8

Author(s):

Janelle Cyprich ◽

Dhiraj J. Pangal ◽

Martin Rutkowski ◽

Daniel A. Donoho ◽

Mark Shiroishi ◽

...

Keyword(s):

Pituitary Adenomas ◽

Vision Loss ◽

Underserved Populations ◽

Pituitary Tumors ◽

Safety Net ◽

Postoperative Outcomes ◽

Endoscopic Endonasal ◽

Cavernous Sinus Invasion ◽

Safety Net Hospital

OBJECTIVESociodemographic disparities in health outcomes are well documented, but the effects of such disparities on preoperative presentation of pituitary adenomas (PA) and surgical outcomes following resection are not completely understood. In this study the authors sought to compare the preoperative clinical characteristics and postoperative outcomes in patients undergoing PA resection at a private hospital (PH) versus a safety-net hospital (SNH).METHODSThe authors conducted a retrospective review over a 36-month period of patients with PAs who underwent endoscopic endonasal transsphenoidal surgery performed by the same attending neurosurgeon at either a PH or an SNH at a single academic medical institution.RESULTSA total of 92 PH patients and 69 SNH patients were included. SNH patients were more likely to be uninsured or have Medicaid (88.4% vs 10.9%, p < 0.0001). A larger percentage of SNH patients were Hispanic (98.7% vs 32.6% p < 0.0001), while PH patients were more likely to be non-Hispanic white (39.1% vs 4.3%, p < 0.0001). SNH patients had a larger mean PA diameter (26.2 vs 22.4 mm, p = 0.0347) and a higher rate of bilateral cavernous sinus invasion (13% vs 4.3%, p = 0.0451). SNH patients were more likely to present with headache (68.1% vs 45.7%, p = 0.0048), vision loss (63.8% vs 35.9%, p < 0.0005), panhypopituitarism (18.8% vs 4.3%, p = 0.0031), and pituitary apoplexy (18.8% vs 7.6%, p = 0.0334). Compared to PH patients, SNH patients were as likely to undergo gross-total resection (73.9% vs 76.1%, p = 0.7499) and had similar rates of postoperative improvement in headache (80% vs 89%, p = 0.14) and vision (82% vs 84%, p = 0.74), but had higher rates of postoperative panhypopituitarism (23% vs 10%, p = 0.04) driven by preoperative endocrinopathies. Although there were no differences in tumor recurrence or progression, loss to follow-up was seen in 7.6% of PH versus 18.6% (p = 0.04) of SNH patients.CONCLUSIONSPatients presenting to the SNH were more often uninsured or on Medicaid and presented with larger, more advanced pituitary tumors. SNH patients were more likely to present with headaches, vision loss, and apoplexy, likely translating to greater improvements in headache and vision observed after surgery. These findings highlight the association between medically underserved populations and more advanced disease states at presentation, and underscore the likely role of academic tertiary multidisciplinary care teams and endoscopic PA resection in somewhat mitigating sociodemographic factors known to portend poorer outcomes, though longer-term follow-up is needed to confirm these findings.

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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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MON-319 Impact of Tumor Characteristics and Preoperative IGF-1 Levels on Postoperative Hormonal Remission Following Endoscopic Transsphenoidal Surgery in Patients with Acromegaly: A Single-Surgeon Series

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.994 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Tyler Cardinal ◽

Martin Rutkowski ◽

Tanu Patel ◽

Mark Shiroishi ◽

John David Carmichael ◽

...

Keyword(s):

Growth Hormone ◽

Medical Therapy ◽

Tumor Control ◽

Subtotal Resection ◽

Tumor Diameter ◽

Endoscopic Endonasal ◽

Cavernous Sinus Invasion ◽

Biochemical Remission ◽

Craniofacial Features

Abstract Introduction: Acromegaly is a potentially fatal neuro-endocrinopathy caused by a growth hormone (GH)-secreting pituitary adenoma (PA). A lack of consensus on factors that reliably predict patient outcomes in acromegalic patients following endoscopic endonasal approaches (EEA) warrants additional investigation. Methods: Pre- and postoperative tumor and endocrinological characteristics from 55 acromegalic patients who underwent EEA for resection of a GH-secreting PA were evaluated as potential predictors of postoperative hormonal remission (defined as age- and sex- normalized IGF-1 levels). Results: The 55 patients included had a mean age of 50.1 ± 13.5 years and a mean follow-up time of 18 ± 17.4 months. Fifty-three patients (96%) presented with dysmorphic craniofacial features, with 22 (40%) presenting with prognathism, 22 (40%) exhibiting frontal bossing, and 18 (33%) presenting with macroglossia. Ten (18%) had microadenomas and 45 (82%) had macroadenomas. Five (9.4%) had giant adenomas. Forty-five (92%) tumors were invasive, with 44 (83%) exhibiting infrasellar invasion, 17 (32%) extending above the sella, and 9 (18%) with cavernous sinus invasion. Thirty-three patients (66%) underwent gross total resection (GTR; mean maximal tumor diameter = 1.52 cm), and 17 (34%) underwent subtotal resection (STR; mean maximal tumor diameter = 2.77 cm). Invasive tumors were significantly larger and Knosp scores were negatively correlated with GTR. Thirty-three patients (65%) achieved hormonal remission after EEA resection alone, which increased to 80% with adjunctive medical therapy. Additionally, 90% of patients who underwent GTR and 63% of patients who underwent STR demonstrated postoperative remission. Six patients (11%) exhibited biochemical remission after postoperative medical therapy with an average time to remission of 5.2 months. These patients all had significantly higher preoperative IGF-1 levels and larger tumors than patients who remitted immediately postoperatively. In all patients preoperative IGF-1 levels were inversely correlated with hormonal remission. Conclusions: This study indicates that endoscopic transsphenoidal resection of growth hormone secreting pituitary adenomas is a safe and highly effective management strategy for achieving hormonal remission and tumor control for patients with acromegaly. When combined with postoperative medical therapy, we observed endocrinological remission rates of 80% based on normalized IGF-1 levels. Our results support the conclusions of current literature that smaller and less invasive tumors are more likely to be fully resected. We additionally suggest that patients with lower preoperative IGF-1 are more likely to undergo postoperative biochemical remission, irrespective of tumor size and invasion.

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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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