Surgery For Acromegaly Research Articles

Outcome of endoscopic transsphenoidal surgery for acromegaly: Comparison of using and not using the floor standing pneumatic powered endoscope-holder system

IntroductionEndoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system. MethodsEndoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes. ResultsThere was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0–2), and low revised Knosp grade (0–3A). In the conventional Knosp grade 0–2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0–3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44. ConclusionThe outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.

Obstructive Sleep Apnea Screening and Effects of Surgery in Acromegaly: A Prospective Study.

To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with acromegaly. We prospectively enrolled adults with acromegaly scheduled for endoscopic transsphenoidal surgery. All measurements were conducted when participants were admitted for a baseline work-up for acromegaly before surgery and surveillance approximately 3 to 6 months after surgery. Respiratory event index (REI) was used as a surrogate for apnea-hypopnea index (Trial Registration: NCT03526016). Of the 35 patients with acromegaly (median age, 47 years; 40% men; median body mass index, 24.4 kg/m2), 24 (68.6%) had OSA (REI ≥5/hour), 15 (42.9%) had moderate-to-severe OSA (REI ≥15/hour). At baseline, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with the REI (ρ=0.53, P=0.001). The sensitivity and negative predictive value of a Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, age, Neck circumference, and Gender (STOP-Bang) score ≥ 3 were 93.3% and 87.5%, respectively, detecting moderate-to-severe OSA. Biochemical acromegaly remission was achieved in 32 (91.4%) patients. The median difference in the REI was -9.5/hour (95% confidence interval, -13.3 to -5.3). Half of the 24 patients diagnosed with OSA preoperatively had REI <5/hour postoperatively. In a linear mixed-effects model, changes in the REI across surgery were related to changes in IGF-1 levels. The STOP-Bang questionnaire is a reliable tool for OSA among patients with acromegaly. Improvement in OSA severity after surgery is related to decreased IGF-1 levels.

THU063 Somatostatin Analog Neoadjuvant Treatment Before Endoscopic Surgery For Growth-Hormone Producing Pituitary Adenomas Invading The Cavernous Sinus: Case Series, Systematic Literature Review And Meta-analysis

Abstract Disclosure: B. Rapoport: None. A. Halstrom: None. A. Kelly: None. M. Roytman: None. J. Lantos: None. D. Phillips: None. R. Ramakrishna: None. T. Schwartz: None. G.A. Dobri: None. Background: Pituitary surgery remains the first line of treatment for acromegaly, yet 35-50% of patients with macroadenomas do not achieve biochemical remission postoperatively. Macroadenomas invading the cavernous sinus (Knosp grades 3 and 4) are particularly refractory to surgical management. Adjuvant therapy with somatostatin analogs in refractory cases is well established, but neoadjuvant use of these agents to consolidate invasive tumors prior to surgery remains controversial. Methods: We retrospectively analyzed our series of 84 consecutive cases of acromegaly treated with endoscopic transsphenoidal pituitary surgery between 2004 and 2020. We have used neoadjuvant pretreatment with somatostatin analogs for adenomas invading the cavernous sinus since 2017. We compared radiographic and long-term biochemical outcomes in the first 10 of these patients with a cohort of historical control patients who underwent resection only. We also performed a systematic review and meta-analysis of studies investigating neoadjuvant use of somatostatin analog therapy prior to transsphenoidal surgery for acromegaly. Results: Neoadjuvant therapy significantly reduced total tumor volume and volume of tumor in the cavernous sinus prior to surgery (mean reductions 30% and 48%, respectively, p&amp;lt;0.01), and was associated with trends toward increased rates of gross total resection and biochemical cure. Of those pretreated with neoadjuvant therapy, 60% were found to be in biochemical remission postoperatively compared to 50% in the control group, P 1. In addition, 70% of those pretreated had a gross total resection compared to 50% of controls, P 0.65. Gross total resection was achieved in all patients with Knosp grade 3 tumors, regardless of pretreatment status, and all of these patients entered biochemical remission. In patients with Knosp grade 4 tumors, gross total resection was achieved in 29% of surgery-only patients and 57% of pretreated patients; biochemical remission was achieved in 14% of surgery-only patients, and 29% of pretreated patients. The differences were not statistically significant. Conclusions: In this series of acromegalic patients with macroadenomas invading the cavernous sinus, neoadjuvant somatostatin analog therapy was associated with a trend toward increased rates of gross total resection and biochemical remission. Of note, those who were not in remission in the pretreatment group had a milder biochemical elevation and required lower-intensity medical therapy postoperatively. The systematic literature review and meta-analysis that we have performed confirm a statistically significant increase in remission rate in patients receiving neoadjuvant therapy. Presentation: Thursday, June 15, 2023

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway

PurposeSustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors.MethodsPatients operated for GH-secreting pituitary adenomas between 2005–2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control.ResultsA total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38–59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96–0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57–1.00), p = 0.053).ConclusionIn unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

A challenging-to-manage biphasic response following pituitary surgery for acromegaly

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictive factors of biochemical remission after transsphenoidal surgery in acromegaly

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Assessment of clinical and histopathological predictors for remission after transsphenoidal surgery for acromegaly

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Determinants of immediate and long-term remission after initial transsphenoidal surgery for acromegaly and outcome patterns during follow-up: a longitudinal study on 659 patients.

Treatment outcomes following initial transsphenoidal surgery (TSS) for acromegaly are erratic. Identifying outcome patterns can assist in informing patients about possible treatment outcomes and planning for individualized adjuvant treatments in advance. In this study, the authors aimed to investigate the immediate and long-term endocrine remission rates following initial TSS for acromegaly, identify clinical determinants of treatment outcomes, and explore outcome patterns during a long-term follow-up and the pattern-specific patient features. This prospective, single-center, longitudinal cohort study enrolled patients with acromegaly who underwent TSS in the period from 2015 to 2018 at the authors' institution. Immediate remission, assessed on the 2nd postoperative morning, and long-term remission, assessed at least 18 months after TSS, were evaluated according to the strict 2010 consensus criteria (random growth hormone [GH] < 1 ng/ml or GH nadir < 0.4 ng/ml after oral glucose tolerance test, and age- and sex-normalized insulin-like growth factor 1). Univariate and bivariate regression analyses were used to identify determinants of remission. A total of 659 patients with acromegaly (average age 42 years, 44% males) underwent TSS for pituitary adenomas (macroadenomas, 85%; invasive tumors, 35%) and were followed up during a median of 51 months. Immediate and long-term remission rates after initial TSS were 37% and 69%, respectively. Older age at diagnosis (OR 1.7), male sex (OR 1.6), smaller tumors (OR 2.0), noninvasive tumors (OR 4.8), and tumors positive for follicle-stimulating hormone/luteinizing hormone (OR 1.5) were predictors of immediate surgical remission. In addition to the above predictors, lower preoperative GH (OR 2.4), absence of preoperative central hypothyroidism (OR 2.6), and endoscopic TSS (OR 10.6) were predictors of long-term remission. Regression analyses revealed that endoscopic TSS (OR 2.8, 95% CI 1.524-5.291, p = 0.001), absence of cavernous sinus invasion (OR 4.1, 95% CI 2.522-6.613, p < 0.001), older age (OR 1.03, 95% CI 1.006-1.048, p = 0.013), and male sex (OR 2.0, 95% CI 1.224-3.247, p = 0.006) were independent determinants of long-term remission. Five outcome patterns were identified based on the changes in hormonal results during follow-up, including continuous remission (34%), refractory acromegaly (28%), delayed remission (21%), remission after adjuvant therapy (14%), and recurrence after initial remission (3%). The clinical characteristics of each subgroup were identified. Cavernous sinus invasion, age at diagnosis, and sex are the best determinants of immediate and long-term remission after initial TSS for acromegaly. Endoscopic TSS predicts a higher long-term remission rate than that with microscopic TSS. The authors identified five outcome patterns in acromegaly and group-specific patient characteristics for clinical decision-making.

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.

Surgery for acromegaly: Indications and goals.

Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.

Cerebral Salt Wasting after Pituitary Surgery for Acromegaly: A Case Report

Cerebral salt wasting, a rare complication of cranial neurosurgery, has not been reported after a functional pituitary tumor resection. The simultaneous presentation of diabetes insipidus (DI) and cerebral salt wasting after pituitary surgery presents a unique diagnostic challenge. We present a case of a 27 y.o. man with a 6-month history of acromegaly as evident by an IGF-1 of 1040 ng/mL (reference range: 101-307 ng/mL). MRI of the pituitary revealed a 3.2 cm × 3.2 cm × 3.1 cm macroadenoma extending beyond the sella turcica.

Endoscopic surgery for acromegaly: results and predictors of outcome from a 22-year experience of a referral Pituitary Centre

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Surgery for acromegaly: Indications and goals

Surgery for acromegaly: Indications and goals

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Machine learning-based clinical outcome prediction in surgery for acromegaly

PurposeBiochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly.MethodsUsing data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed.ResultsThe derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59–0.88) for GTR, 0.63 (0.40–0.82) for BR, as well as 0.77 (0.62–0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively.ConclusionsGross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission

Background Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. Objective To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. Methods A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. Results A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. Conclusion Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

Value of Early Post-Operative Growth Hormone Testing in Predicting Long-Term Remission and Residual Disease after Transsphenoidal Surgery for Acromegaly

Introduction: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. Methods: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2–5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir <0.4 μg/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. Results: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 ± 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of <0.4 (N = 43), between 0.4 and 1 (N = 28), and >1 μg/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). Conclusions: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.

Impact of Experience on Outcomes After Endoscopic Transsphenoidal Surgery for Acromegaly

Acromegaly is a syndrome of metabolic alterations secondary to increased growth hormone levels from a somatotroph pituitary adenoma. A multidisciplinary approach beginning with surgery, followed by adjuvant radiation or medical therapy for residual disease, is considered standard of care. Several factors affect the likelihood of remission after surgery, but the impact of surgical experience on remission rates has not been adequately assessed. Retrospective review of 203 patients, divided into 2 eras (era 1, 102 patients; era 2, 101 patients) of patients who underwent transsphenoidal surgery for acromegaly by a single surgeon over 11 years, was performed, determining the effect of surgical experience on rates of remission and various complications. Remission was defined according to the 2014 Endocrine Society Clinical Practice Guideline. The rate of surgical remission was 40.6% (62.9% among noninvasive adenomas). Rates of surgical remission significantly improved in the latter half of this cohort (31.2% in the first half vs. 50% in the second half), despite other factors being comparable. On multivariate analysis, surgeon experience, cavernous sinus invasion, and preoperative growth hormone levels affected the rates of surgical remission. Rates of cerebrospinal fluid leak and hypopituitarism were lower in the second half, whereas resolution of acromegaly-associated comorbidities was increased. We report, in this large single-surgeon review of endoscopically operated acromegaly cases, increased rates of surgical remission and reduced complications with increasing surgeon experience. The overall experience of the treating team in dealing with perioperative and intraoperative factors also contributes to improved outcomes.

Transsphenoidal surgery in acromegaly: Experience in a tertiary hospital

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study.

ContextTranssphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy.ObjectiveTo identify predictors for remission after TSS in acromegaly.MethodsLarge multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n = 282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction.ResultsA larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P ≤ .0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P = .0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P = .0053) were associated with a lower chance of long-term remission.ConclusionMaximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.