Preoperative Growth Hormone Research Articles

Preoperative predictors of biochemical remission in somatotroph adenoma resections: a single-institution retrospective review.

There is persistent debate in the literature surrounding the true predictors of biochemical remission after resection of somatotroph adenoma. A multimodal analysis of a large number of patients is needed to better understand which patients may be at higher or lower risk for remission failure after surgery. A retrospective review was performed on patients undergoing somatotroph adenoma resection. Biochemical remission was defined as age- and sex-adjusted normalization of serum insulin growth factor-1 (IGF-1) levels at least 6 months after surgery. Patient case characteristics and clinicopathologic variables were tested for statistical associations with remission and were included in a random forest machine learning model to assess for their importance in determining remission status. Preoperative variables found to be significant remission predictors on statistical testing and important in the random forest model were subsequently assessed via receiver operating characteristic (ROC) analysis to determine numeric thresholds that optimally predicted preoperative likelihood of remission success or failure. Eighty patients were identified with somatotroph adenoma who underwent transsphenoidal resection, with 60 patients (75%) achieving biochemical remission. Statistical testing found that patients with failed remission were more likely to have larger tumors (1.9 vs 1.6 cm by the largest axis, p = 0.014; and 3.61 vs 2.66 cm3 by 3D volume, p = 0.013) that invaded the cavernous sinus more frequently (70% vs 22% of patients, p < 0.001) and have higher preoperative IGF-1 level (860 vs 660 ng/ml, p = 0.044). An optimized random forest machine learning model with 10,000 iterations found that tumor size, preoperative growth hormone and IGF-1 levels, and cavernous sinus invasion were important preoperative predictors of remission status. ROC analysis revealed that 96% of patients with preoperative 3D tumor volume less than 1.51 cm3 (area under the curve [AUC] 0.691, p = 0.003) and 100% with nonadjusted preoperative IGF-1 level less than 718.5 ng/ml (AUC 0.736, p = 0.002) achieved remission. Important preoperative predictors of postoperative remission for somatotroph adenoma resection include serum IGF-1 level, cavernous sinus invasion, and tumor size. Ninety-five percent of patients who achieved postoperative remission had preoperative 3D tumor volume less than 1.51 cm3.

Variable anatomical features of acromegaly in the nasal cavity and paranasal sinuses: implications for endoscopic endonasal transsphenoidal surgery.

Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly. Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed. In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171). The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients.

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.

The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a low Risk of Recurrence in Acromegaly.

a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype. To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure. Retrospective, observational study. Two tertiary care centers. We investigated 254 patients with acromegaly who were cured by surgery. All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar). Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04). our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.

Management of growth hormone-secreting pituitary adenomas causing acromegaly: a practical review of surgical and multimodal management strategies for neurosurgeons.

This review aimed to highlight the history, diagnostic criteria, preoperative prognostic factors, surgical management, and multimodal adjuvant therapies recommended to provide a comprehensive and multifaceted understanding of and clinical approach to treating growth hormone-secreting pituitary adenomas (GHPAs) in patients with acromegaly. The authors collated and reviewed published studies, many written by skull base neurosurgeons, endocrinologists, and radiation oncologists with expertise in pituitary adenoma management, to produce a practical and contemporary update pertaining to the optimal management of acromegaly for neurosurgeons. Acromegaly is a debilitating disease for which surgery can be curative in more than two-thirds of patients. Recent rates of hormonal remission by the authors' group and others following the resection of GHPAs are on the order of 70%-80%, and these increase to more than 85% with the addition of medical therapy in a minority of patients who do not achieve remission with surgery alone. Most tumors are accessible via a direct endoscopic endonasal transsphenoidal approach, which can be augmented with a variety of extended approaches to gain access to suprasellar, clival, and parasellar compartments as needed. Preoperative growth hormone levels, cavernous sinus invasion, and pituitary adenoma consistency are important factors in determining the extent of resection. In most patients with residual or recurrent disease, medical therapy (e.g., somatostatin analogs and dopamine agonists) can be used to help achieve hormonal remission. Repeat surgery can be safely performed in most cases if needed, whereas stereotactic radiosurgery is usually reserved for medically resistant tumors in surgically inaccessible compartments. The neurosurgeon has a primary and often definitive role in the management of acromegaly. The involvement of an integrated and multidisciplinary team consisting of experts from neurosurgery, otolaryngology, endocrinology, and radiation oncology optimizes the chances for a biochemical cure, even in large and aggressive GHPAs.

Perioperative hormone level changes and their clinical implications in patients with pituitary adenoma: a retrospective study of 428 cases at a single center.

This study employs case data analysis to elucidate alterations in hormone levels pre and post-surgery among patients with pituitary adenoma. Moreover, it investigates the influence of various associated factors on endocrine function. A retrospective analysis was conducted on clinical data from 428 patients who underwent surgical treatment within a short period at a single center. Statistical methods were employed to examine detailed hormone level fluctuations before and after surgery in patients with pituitary adenoma, along with their interrelations with different factors. Between January 2016 and October 2022, a total of 428 consecutive patients with pituitary adenoma underwent surgical treatment. Of these, 232 were males and 196 were females, with an average age of 45.91 years (range: 16-84, standard deviation: 12.18). Univariate analysis indicated that females exhibited a higher susceptibility to preoperative endocrine dysfunction (p < 0.05). Conversely, males, patients with larger tumor volumes, and older patients were more prone to preoperative pituitary insufficiency. Postoperatively, the most substantial remission rate occurred in prolactin (77.4%), followed by growth hormone (GH) (71.8%) and cortisol (4/6). The highest recovery rate in functions was observed in growth hormone secretion function (80%), followed by pituitary-adrenal axis hormone secretion function (56.3%) and pituitary-thyroid axis hormone secretion function (47.5%). The most noteworthy incidence of newly developed postoperative endocrine deficiencies was found in the pituitary-adrenal axis (31.8%), while the occurrence rates of deficiencies in other axes were relatively low. The elevated postoperative remission rate of growth hormone correlated with a higher surgical resection rate and lower preoperative growth hormone levels. Additionally, lower preoperative prolactin levels corresponded to a higher remission rate of prolactin postoperatively. Furthermore, the restoration of postoperative thyroid hormone secretion function was associated with higher preoperative free thyroxine levels. Reduced postoperative cortisol secretion function was linked to multiple surgeries and an extended interval between hormone retesting and surgery. Surgical intervention effectively ameliorates endocrine disorders in pituitary adenoma patients, thereby mitigating symptoms and enhancing their quality of life. Preoperative management of growth hormone and prolactin levels facilitates an increased remission rate of these hormones post pituitary adenoma surgery. Patients displaying preoperative thyroid hormone secretion dysfunction should be considered for active supplementation therapy. Whenever feasible, complete tumor resection is recommended. For patients undergoing reoperation or multiple surgeries, vigilant postoperative cortisol monitoring and supplementation should be thoughtfully administered.

THU044 The Subcellular Localization Of β-Catenin Is Associated With Tumor Size And The Surgical Remission Rate In Growth Hormone-producing Pituitary Adenomas

Abstract Disclosure: S. Kuwabara: None. H. Kameda: None. H. Nomoto: None. K. Cho: None. A. Nakamura: None. Y. Ishi: None. H. Motegi: None. F. Miki: None. H. Miyoshi: None. T. Atsumi: None. The Wnt/β-catenin pathway is the best understood Wnt signaling pathway and controls cell proliferation. In the presence of Wnt, the translocation of β-catenin from the cytoplasm to the nucleus leads to pathway activation. It has been reported that the nuclear accumulation of β-catenin is associated with Ki-67 expression in pituitary adenomas and that the invasiveness of growth hormone (GH)-producing pituitary adenomas is associated with β-catenin expression. We aimed to clarify the effects of the Wnt/β-catenin pathway in GH-producing pituitary adenomas. We performed immunofluorescence staining using antibodies against GH and β-catenin in pathological samples of pituitary adenoma from 62 patients with acromegaly who underwent pituitary surgery at our hospital between January 2008 and December 2021. We also obtained clinical data for the patients, including the results of endocrine testing, and evaluated the relationships of key indices with the intracellular localization of β-catenin. Samples from 26 cases (42%) showed strong punctate expression of β-catenin in the nuclei (dot pattern (DP) group), and samples from 36 cases (58%) showed β-catenin expression in the cytoplasm or cell membrane (non-DP group). There were no differences in the sex, age, GH concentration, or insulin-like growth factor I (IGF-1) SD scores of the two groups, but the DP group had larger tumors (diameters 18±8 vs. 13±7 mm) and a higher prevalence of macroadenomas (77% vs. 53%). In the DP group, a paradoxical preoperative GH response (an increase of ≥30% of the basal concentration) to 75-g oral glucose tolerance testing was more frequent (46 vs. 22%, p&amp;lt;0.05) and postoperative remission was less frequent (23% vs. 50%, p&amp;lt;0.05). Accordingly, the Wnt/β-catenin pathway appears to be more active in the DP group. The larger tumors and lower postoperative remission rate of the DP group suggest that the Wnt/β-catenin pathway may influence tumor growth. Wnt/β-catenin pathway could play a major role in GH-producing pituitary tumor growth, therefore this pathway would be a potential therapeutic target in the affected patients. Presentation: Thursday, June 15, 2023

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

Self-reported symptoms in patients with acromegaly: a 6-month follow-up in a single neurosurgical center.

Acromegaly is characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), accompanied by a compromise in the perception of wellness. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) is relevant to assessing signs and symptoms but is mainly used to evaluate the efficacy of a pharmacological intervention. To explore the perioperative variation in symptom severity, the divergence between subgroups stratified according to clinical outcomes or treatment modalities, and the interaction between symptom scores and clinical indices, we prospectively recruited 106 patients with acromegaly from 2016 to 2018. Oral glucose tolerance and GH tests were performed, and PASQ was administered before treatment and 6 months postoperatively. Patients were divided into active (n = 49) and remission (n = 57) groups according to postoperative GH and IGF-1 levels. PASQ scores and GH and IGF-1 levels decreased significantly postoperatively in both groups. A significantly higher preoperative headache score and greater extent of decrease in arthralgia were seen in the active and remission groups, respectively. No significant variation in PASQ scores was found between patients receiving surgery alone and those receiving preoperative somatostatin analogs. Preoperative fasting GH (GH0) levels were positively correlated with preoperative excessive perspiration. Further regression analyses validated the variation in GH0 as a noteworthy determinant of the extent of change in soft-tissue swelling, excessive perspiration, fatigue, and total PASQ scores. Patient-reported symptoms were substantially alleviated after surgery, independent of endocrine remission or use of preoperative somatostatin. A GH level decrease was a notable coefficient for PASQ scores.

The Prognostic-Based Approach in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors (PitNET): Tertiary Reference Center, Single Senior Surgeon, and Long-Term Follow-Up

Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26-156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy's and Knosp's grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp's grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp's grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.

Delayed postoperative hyponatremia in patients with acromegaly: incidence and predictive factors.

Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the twogroups. The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

Machine learning as a clinical decision support tool for patients with acromegaly

To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. ML models may serve as valuable tools in the prediction of remission and SRL resistance.

High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

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.

Predictors of postoperative biochemical remission in acromegaly.

Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3months in patients after surgery. Of the 546 surgical cases (mean age: 36.8years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28μg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28μg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

MON-310 Factors Associated with Remission After Surgery for Acromegaly

Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas. Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma. Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test <0.4 ng/mL. Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (<2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006). Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.

The acromegaly registry of ten different centers in Turkey

ObjectivesTo describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. MethodsRetrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. ResultsA total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. ConclusionsThis is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Preoperative growth hormone (GH) peak values during a GH releasing peptide-2 test reflect the severity of hypopituitarism and the postoperative recovery of GH secretion in patients with non-functioning pituitary adenomas.

Non-functioning pituitary adenoma (NFPA) is one common cause of adult growth hormone deficiency (AGHD). In Japan, a GH-releasing peptide (GHRP)-2 test is used to evaluate GH secretion. Although the cut-off for peak GH during a GHRP-2 test for severe AGHD is ≤9 ng/mL, severe AGHD may further diminish responses (range, nearly no-response to ≤9 ng/mL). We studied whether the peak GH responses during a GHRP-2 test could be predicted based on clinical characteristics of patients with NFPA. We compared patients with almost no-response during a GHRP-2 test with other patients considered as severe AGHD. Among the 76 patients with NFPA who were admitted to our institution, 36 patients (mean age, 61 years; male/female, n = 23/n = 13) were diagnosed with severe AGHD based on a preoperative GHRP-2 test. Based on the preoperative median peak GH concentration (2.83 ng/mL), patients were divided into two groups (<median = low or group L, n = 18; ≥median = moderate or group M, n = 18). Clinical manifestations, body mass index, severity of hypopituitarism and tumor size, volume, and extension were analyzed retrospectively. Compared with group M, group L patients were significantly older and more gonadotropin and ACTH deficient. A lower peak GH release during a GHRP-2 test was associated with a higher number of anterior pituitary hormone deficiencies across all 76 patients. Postoperatively, seven in group M and no patient in group L were assessed as having no longer severe AGHD, respectively. Preoperative peak GH concentrations assessed during a GHRP-2 test reflected the severity of hypopituitarism and the recovery of postoperative GH secretion.