Transsphenoidal Surgery Research Articles

USE OF AUGUMENTED REALITY IN TREATMENT OF PITUITARY MICROADENOMAS

Introduction Transsphenoidal surgery, performed using endoscopic or microscopic techniques, is a safe and effective method for treating neuroendocrine pituitary tumors, including microadenomas. However, the precise location of microadenomas can be challenging to determine, particularly in acromegaly patients, who often exhibit a reduced intracarotid distance. Augmented reality (AR), particularly through heads-up displays (HUD) integrated into surgical microscopes, has been predominantly utilized in transcranial approaches but shows potential in enhancing transsphenoidal procedures. Aim This study aims to present the surgical workflow, techniques, and outcomes associated with using AR in microscopic transsphenoidal surgery for pituitary microadenomas. Material and Methods All procedures were conducted at the Targu Mures Clinical Emergency Hospital’s Department of Neurosurgery between 2019 and 2024. A total of 15 cases were treated using AR-assisted techniques. While the surgical operative time was comparable to non-AR-assisted procedures, the preoperative setup was more time-consuming and required staging to optimize the surgical workflow. In all cases, surgeons successfully identified and resected the microadenomas without complications related to navigation accuracy. Conclusions The findings suggest that integrating AR into transsphenoidal surgery enhances anatomical understanding and precise localization of microadenomas, providing a valuable tool for neurosurgeons. However, AR cannot replace surgical expertise and clinical judgment.

CTNI-34. A RANDOMIZED PROSPECTIVE TRIAL OF POST-OPERATIVE FLUID RESTRICTION TO DECREASE THE INCIDENCE OF DELAYED HYPONATREMIA AND READMISSION AFTER TRANSSPHENOIDAL SURGERY

Abstract BACKGROUND Delayed hyponatremia (hypoNa) is the leading cause of readmission following transsphenoidal surgery (TSS). Some institutions have adopted post-operative fluid restriction (FR) protocols based on retrospective studies. We present results of a prospective randomized controlled trial evaluating post-TSS FR. METHODS 300 participants scheduled for TSS (2016-2023) at a single institution were included. Patients with CKD, CHF, AVP deficiency on postoperative day (POD) 3, chronic hypoNa, untreated adrenal insufficiency/hypothyroidism, and those for whom FR was felt unsafe were excluded. Patients were randomly assigned to control (CON, n=94) or moderate FR (FR1, n=39). Participants in CON group were instructed to drink ad lib. Participants in FR1 were FR to 1.8 liters/day (2 liters/day if > 100 kg) from POD3-14. Based on interim analysis suggesting a trend toward reduced hypoNA, FR was changed to strict FR (FR2, n=62) of 1 liter/day (1.2 liters/day if > 100 kg). Serum sodium (Na) was monitored inpatient and on POD 3, 7, 10, and 14, and readmissions evaluated. Fluid intake and thirst were assessed. RESULTS In the intention-to-treat analysis, incidence of hypoNa (Na < 135 mEq/L) was 31.9% CON, 28.2% FR1, and 21% FR2, and severe hypoNa (Na < 125 mEq/L) 7.4% CON, 5.1% n FR1 and 0% FR2. Readmission for hypoNa occurred in 6.4% (n=6) CON, 7.7% (n=3) FR1 and 1.6% (n=1) FR2. Severe hypoNa occurred more frequently in CON vs. FR2 (P=0.04), and nadir Na was higher in FR2 vs. CON (P=0.02). Although thirst scores were similar among groups, an individual’s thirst score correlated with compliance CONCLUSION Results of this randomized study show a reduction in severe hypoNa and readmission for hypoNa in patients on FR from POD3-14 after TSS vs. patients instructed to drink ad lib. This provides strong evidence that post-TSS FR decreases rate of delayed hypoNa and related readmission.

SURG-56. TRANSCRIPTION FACTOR CELL LINEAGE DETERMINES AGGRESSIVE BEHAVIOR AMONG NONFUNCTIONAL PITUITARY ADENOMAS

Abstract INTRODUCTION Pituitary neuroendocrine tumors (PitNETs) are the second most common intracranial neoplasm. Silent or non-functional PitNETs represent a common neuro-oncological challenge due to their size and unpredictable invasion of parasellar structures. This makes their complete surgical resection difficult and puts patients at higher risk for recurrence. OBJECTIVE To characterize differences in tumor volume, cavernous sinus invasion, and recurrence in nonfunctional PitNETs. METHODS Out of 615 transsphenoidal surgeries from 2012 to 2024, there were 309 overall PitNETs and 181 nonfunctional PitNETs. Based on new WHO criteria for transcription factor profiling (PIT-1, TPIT, and SF-1), there were 98 silent gonadotroph adenomas (SGA), 31 silent corticotroph adenomas (SCA), 10 silent pleurihormonal tumors (PHT), and 2 null cell adenomas. Tumor volume was calculated using (AxBxC/2). Knosp grade was calculated. Cavernous sinus invasion was defined as Knosp ≥ 3. Residual disease at 3 months postoperative was recorded and surgical intervention for growing residual disease was captured. RESULTS Average tumor volume of PHT (18.08 cm3) was significantly higher than SGA (8.44 cm3, p=0.007) and similar to SCA (10.33 cm3, p=0.11). Percentage of cavernous sinus invasion was significantly different between SCA (31.82%) and SGA (10.20%, p=0.003), but not PHT (33.33%; p>0.05). There was a significantly higher residual rate in SCA compared to SGA (31.71% vs. 11.22%, p=0.006). There were significantly more reoperations in the SCA group compared to SGA and PHT. CONCLUSIONS Despite similar tumor volume between SCA and SGA, there was a significantly higher rate of cavernous sinus invasion and residual disease among SCA. This has important neuro-oncological implications regarding surgical technique, postoperative surveillance, and need for adjuvant therapy to mitigate aggressive recurrent disease.

NIMG-20. DWIBS FOR PRIMARY CANCER DETECTION IN INTRACRANIAL METASTASIS: TWO CASE REPORTS

Abstract INTRODUCTION Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis. CASE PRESENTATION Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung. DISCUSSION While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited. CONCLUSION Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.

Causes and treatment of secondary sphenoid sinus infection post-endoscopic transsphenoidal approach.

This study analyzed the causes of sphenoid sinus (SS) infection (SSI) following endoscopic transsphenoidal skull base surgery and determined appropriate treatment methods. This study included 31 cases of secondary SSI following the endoscopic transsphenoidal approach (ETSA; SSI group) and 246 cases without SSI (non-SSI group). Data collected included post-ETSA pathological results, types of artificial skull base reconstruction materials, and SS patency. For the SSI group, data included time from ETSA to symptom onset, endoscopic and imaging findings, intraoperative conditions during the second surgery, and changes in visual analog scale (VAS) scores. The incidence of secondary SSI was 11.19%. In the SSI group, 26 patients (83.87%) reported headaches, and 24 (77.42%) had stenosis or closure of the SS ostium (SSO). The non-SSI group reported no symptoms, and 236 patients (95.93%) had well-opened SSOs. Centripetal hyperosteogeny (CHO) in the SS walls was observed in 20 patients (64.5%) in the SSI group. Absorbable materials were used in five cases (16.13%) and 215 cases (87.40%) in the SSI and non-SSI groups, respectively, while non-absorbable materials were used in 24 cases (77.42%) and 20 cases (8.13%), respectively. SSI risk was 9.42 times higher with non-absorbable synthetic materials. VAS scores for SSI symptoms and Lund-Kennedy scores significantly decreased at 3 and 12 months post-second surgery. Secondary SSI after ETSA can cause persistent symptoms. Non-absorbable synthetic repair materials should be avoided to prevent secondary SSI. Extended sphenoidectomy and removal of artificial materials can lead to rapid resolution of SSI symptoms. 4.

The learning curve and outcomes of 1038 endoscopic endonasal transsphenoidal pituitary tumor surgeries – A single surgical team experience

The learning curve and outcomes of 1038 endoscopic endonasal transsphenoidal pituitary tumor surgeries – A single surgical team experience

Successful management of refractory Cushing's disease with severe hypercortisolemia using etomidate and temozolomide in post-surgical failure.

Corticotropinomas account for 20% of all aggressive pituitary tumors and pituitary carcinomas and are associated with high mortality. These tumors not only cause neurovascular compromise but can also be fatal due to severe hypercortisolemia itself. Although surgery is considered the primary treatment modality, it is often partially successful or unsuccessful. Moreover, these tumors frequently recur and may be resistant to conventional treatments, including surgery and radiotherapy. Therefore, early multimodal treatment and regular follow-up are necessary. We present a case of aggressive Cushing's disease managed with combined temozolomide therapy and radiotherapy following an unsuccessful transsphenoidal surgery, resulting in significant long-term radiological and biochemical remission. In addition, etomidate infusion was administered to achieve rapid cortisol reduction, highlighting its role as a bridging therapy to other modalities in treating life-threatening and severe hypercortisolemia outside an intensive care setting.

PATHOPHYSIOLOGY AND MANAGEMENT OF CUSHING SYNDROME: A SYSTEMATIC REVIEW OF CURRENT AND FUTURE PERSPECTIVES

Objective: The general objective of this study is to analyze the scientific literature on Cushing's Syndrome (CS), seeking to identify the main clinical manifestations, complications, and the impact on patients' quality of life. Methodology: Searches were performed in the PubMed Central (PMC) databases, using three descriptors in combination with the Boolean term “AND”: Cushing Syndrome, Clinical Manifestations, Complications, and Quality of Life. A total of 161 articles were found, which were subsequently submitted to the selection criteria. Twenty-two studies were selected to compose this systematic review, of which 12 were used. Results: Cushing's Syndrome is a condition characterized by hypercortisolism, which results in a wide range of clinical manifestations. Complications associated with CS include visceral obesity, arterial hypertension, diabetes mellitus, dyslipidemia, osteoporosis, and myopathy. In addition, CS has a significant impact on patients' mental health, including depression, anxiety, and cognitive impairment. Therapeutic approaches range from transsphenoidal surgery, radiotherapy, to targeted drug treatments to normalize cortisol levels and address comorbidities. Conclusion: CS is associated with several comorbidities that affect multiple body systems, resulting in a significant impact on patients' quality of life. Early diagnosis and multidisciplinary treatment are essential to improve clinical outcomes and quality of life in these patients.

Wrapping method for better fat handling in endoscopic trans-sphenoidal surgery.

Fat is commonly used for preventing cerebrospinal fluid (CSF) leakage during endoscopic transsphenoidal surgery (ETSS). However, fat is soft, slippery, and sometimes not easy to handle. The present study aimed to examine the efficacy of our Surgicel® wrapping method, which allows for better fat handling, in preventing the occurrence of CSF leakage among patients undergoing ETSS. We used fat tissues removed from the abdomen. The fat was cut with scissors into pieces that were approximately 5 mm in size. Surgicel® was also cut into 2.5 cm2. The fat tissues were encased with these Surgicel® squares and slightly moistened with a saline solution. Between January 2023 and August 2024, 34 patients aged 18-86 years (average 54.9 years) underwent ETSS. Among these patients, 20 had pituitary tumors, 6 had Rathke's cysts, and 8 had other conditions. None of the patients had CSF leakage postoperatively. The use of Surgicel®-wrapped fat during ETSS is better than the use of fat alone. The Surgicel® wrapping method allows for better fat handling during ETSS.

Long-Term Quality of Life Among Patients Undergoing Endoscopic Pituitary Gland Surgery.

Introduction/Objectives: The endoscopic approach to skull base lesions is widely regarded as less invasive and associated with reduced morbidity, offering favorable outcomes, particularly in terms of short-term quality of life (QOL). However, to date, long-term assessments of both nasal function and tumor-related QOL remain limited. To evaluate patients' long-term nasal- and tumor-related QOL after endoscopic endonasal resection of pituitary tumors and to detect predictors for poor postoperative QOL. Study Design: This study was a prospective cohort study. Methods: All patients with pituitary adenomas who underwent trans-sphenoidal surgery at Tel Aviv Sourasky Medical Center between 2014 and 2021 were recruited. Recruited patients completed the Anterior Skull Base Disease-Specific QOL (ASBS-Q) questionnaire and the Sinonasal Outcome Test 22 (SNOT-22) questionnaire before surgery and 1, 2, and 3-5 years after surgery. Clinical data were collected and analyzed. Results: The study included 43 patients (18 women). No significant decrease was observed in tumor-related quality of life (QOL) scores, measured by ASBS-Q and SNOT-22, throughout the 5-year follow-up period. SNOT-22 score differences from the preoperative baseline at years 1, 3, and 5 were 0.81 [-4.84-6.58], 3.35 [-4.32-11.02], and 3.73 [-2.22-9.68], respectively, with no statistically significant changes. ASBS-Q scores similarly showed no significant changes over time. Subgroup analyses revealed that tumor characteristics (secreting vs. non-secreting, size), surgical factors (intraoperative cerebrospinal fluid leak, gross tumor resection, use of nasoseptal flap), and endocrine remission did not significantly impact QOL (p > 0.05 for all variables). Conclusions: Our study demonstrated that patients who underwent endoscopic pituitary lesion resection maintained high nasal- and tumor-related quality of life over a 5-year follow-up period. However, given the limitations of our study, further multi-center studies with larger patient populations are warranted to validate these results.

Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery

Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

Analysis of the impact of a rhinologist-assisted endoscopic approach on a single neurosurgeon’s outcomes in transsphenoidal resection of pituitary adenomas

ObjectivesDetermine the improvements in outcomes of transsphenoidal pituitary adenoma resection following addition of a skull base rhinologist to the neurosurgical team. DesignAll patients that underwent transsphenoidal resection of pituitary adenoma were identified. Demographic data, Otolaryngology (ENT) involvement, initial adenoma size, extent of resection, hormonal secretion status, visual field exam, post-operative DI, CSF leak, recurrence, need for nasoseptal flap (NSF), re-operation rate were all collected. A linear-regression model adjusteds for confounders. SettingA single academic institution Participants271 patients who underwent transsphenoidal surgery between 2015 and 2020.Main Outcome MeasuresThe main outcome measures were Extent of Resection and Endocrinologic remission. ResultsOf the 271 patients identified, 228 (84 %) patients had macroadenomas, one-third of patients presented with bitemporal hemianopsia, and 27 % (72) were hormonally active. For these and demographics there were no statistically significant differences between the microscopic or endoscopic approach (EEA) groups. For patients with cavernous sinus invasion of >50 %, EEA was more likely to achieve gross total resection (GTR) (OR 2.6; p<0.001). For patients who had prior sellar surgery, EEA was 2.5x more likely to get a GTR (p=0.05). The EEA approach resulted in an extra hospital day (1–2 vs 2–3 p<0.05) and surgery lasted an additional hour (1.17 vs 2.5, p<0.05), but did not require fat grafts or lumbar drains on a routine basis. ConclusionsWhile the operating time and LOS were longer, the EEA approach performed by two specialized co-surgeons demonstrates superior value for adenomas that have had a prior surgical attempt or with significant cavernous sinus invasion.

Extended Endoscopic Transsphenoidal Surgery with Total Cyst Wall Decollement for Suprasellar Cystic Craniopharyngioma: Case Report and Literature Review.

For most cystic craniopharyngiomas, intracapsular debulking is a good strategy to get a large operation space and protect vital structures. However, this surgical strategy may lead to the residual and recurrence of the tumor capsule wall. Therefore, there is an urgent need for a new surgical strategy without residual capsule walls for the removal of cystic craniopharyngiomas. We reviewed a 45-year-old male with vision loss and visual field defects, whose head MRI revealed a suprasellar cystic lesion. The patient underwent extended endoscopic transsphenoidal surgery. The surgical strategy of total cystic wall decollement was adopted, which was that the lesion surrounded by the capsule was completely separated from the surrounding tissue without destroying the capsule and maintaining the tension of the capsule. The lesion was totally resected and pathological findings confirmed the diagnosis of craniopharyngioma. After the operation, both the visual acuity and pituitary function were significantly improved. In addition, he suffered from transient diabetes insipidus, which was subsequently relieved. During the 33-month follow-up, there was no tumor recurrence. Compared with the traditional surgical strategy of intracapsular debulking, the surgical strategy of total cystic wall decollement has the advantages of less residual tumor capsules, low tumor recurrence rates, etc. Therefore, for specific cystic craniopharyngiomas, the surgical strategy of total cystic wall decollement may be an effective surgical strategy to reduce tumor recurrence.

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.

Fluorescence detection of pituitary neuroendocrine tumour during endoscopic transsphenoidal surgery using bevacizumab-800CW: a non-randomised, non-blinded, single centre feasibility and dose finding trial [DEPARTURE trial

Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A). In part I, dose-escalation (0-4∙5-10-25mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10mg and 25mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed. Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10mg (TBR 2∙00 [1∙86, 2∙19]) and 25mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25mg group. With both 10mg and 25mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression. This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10mg and 25mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25mg group. NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov.

7594 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

9272 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

8117 Late-night Salivary Cortisol in the Diagnosis of Cushing's Disease Recurrence

Abstract Disclosure: A.E. Alexandre: None. P.C. Elias: None. M. De Castro: None. L.M. Mermejo: None. D.C. Aragon: None. A.C. Moreira: None. Cushing’s Disease (CD) remission following transsphenoidal surgery (TSS) is most often defined by low morning cortisol levels and the requirement of glucocorticoid (GC) replacement therapy. However, CD recurrence is not a well studied event. There is no standard definition of remission criteria and no accurate cutoff for biochemical tests on CD recurrence. Late-night salivary cortisol (LNSC) has been shown to have higher accuracy in confirming CD recurrence than urinary free cortisol and dexamethasone suppression test (DST). However, few studies addressed LNSC performance following remission after TSS. The study aimed to establish cutoff values of LNSC with higher sensitivity (S) and specificity (E) in CD recurrence diagnosis.In a retrospective cohort study of 65 patients with remitted CD after TSS, remission was defined as improvement of sign and symptoms related to CD and a plasma cortisol &amp;lt;5mcg/dL in 30 days following TSS. Eleven patients progressed to permanent adrenal insufficiency and were excluded from the study. All 54 patients had at least four LNSC sampling and a minimal follow-up of 24 months after TSS. LNSC was determined by RIA. A cutoff value of 270 ng/dl for LNSC is used for the diagnosis of CD. Patients were divided in three different groups: Overt Recurrence (OR): elevated LNSC and worsening of CD`s signs and symptoms. Remission (RM): normal LNSC and no clinical signs of CD recurrence. Biochemical Recurrence (BR): at least 2 elevated biochemical parameters (LNSC or DST) but no worsening of signs and symptoms associated with CD. The mean of the 2 LNSC last values when OR was diagnosed and the mean of 2 LNSC last values of follow up for RM patients were used to estimate the accuracy of LNSC for diagnosing recurrence using a ROC curve (AUC) and its 95% confidence interval. Of the 54 patients included, 46 females; 8 males; mean age at diagnosis: 32 years, (5 – 58 yrs); mean time of follow-up: 12.8 years (4 – 31.7 yrs). Thirteen were classified as OR, 18 as RM and 23 as BR; and mean time of GC use after TSS was: 8.7; 34 and 17 yrs, respectively, significantly lower in OR compared to RM (p:0.046). A LNSC cutoff value of 272 mcg/dL had sensitivity of 85% and specificity of 95% (AUC: 0.97; 95% IC = [0.93; 1,00]) for CD recurrence diagnosis. BR patients presented LSNC fluctuation along follow-up.LNSC is a useful tool for CD recurrence screening. Setting LSNC specific assay cutoff values might be needed. LSNC cutoff values were similar for the initial CD diagnosis, as well as for CD recurrence diagnosis. Shorter time of GC replacement may be an important predictor of CD recurrence. Patients with BR should be followed more carefully as they may be at higher risk of recurrence. Multiple LNSC sampling on successive days can be easily performed and may detect subtle changes in cortisol rhythm. Presentation: 6/1/2024

6570 Treatment of Cushing’s With Levoketoconazole: A Case Series

Abstract Disclosure: N. Chamorro-Pareja: None. M. Haines: None. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Research Investigator; Self; Recordati, NovoNordisk, Perspectum Ltd, Lumos Pharma, Pfizer, Inc.. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. B.M. Biller: Consulting Fee; Self; Xeris Pharmaceuticals, Recordati Rare Diseases, Sparrow, Lundbeck. Background: Endogenous Cushing’s syndrome (CS) is a rare condition of excess cortisol secretion; the most common cause is a pituitary corticotroph tumor (Cushing’s disease [CD]). Medical treatment for CD is primarily used to control hypercortisolism in patients with persistent or recurrent disease after transsphenoidal surgery (TSS). Levoketoconazole (LKCZ), a steroidogenesis inhibitor, was FDA approved in January 2022 for CS treatment. This reports 3 cases of patients who were treated with LKCZ for recurrent CS. Clinical Cases: Case 1: 44-year-old (yo) male (M) with a history of CD with urinary free cortisol (UFC) &amp;gt;26x upper limit of normal (ULN) who was treated preoperatively with ketoconazole (KCZ) 1000 mg/day with UFC improved to 6x ULN. KCZ was discontinued at TSS, and he achieved remission post-operatively. He was lost to follow-up and re-presented after several years with worsening hypertension, muscle weakness, edema, and anxiety with UFC 28x ULN and a recurrent pituitary lesion on MRI. He declined repeat TSS and underwent radiation therapy (RT) and medical treatment. LKCZ was initiated at 150 mg twice daily (BID) and increased to 300 mg BID. At LKCZ 300 mg BID, he had a low UFC and mild nausea but an adequate serum morning cortisol (10.4 ug/dL, ref:6-18.4 ug/dL); LKCZ was reduced to 150 mg BID with resolution of symptoms (sxs) and normal UFC. Case 2: 56 yo M with a history of CD (UFC &amp;gt;3x ULN) who underwent 2 TSSs and RT over 10 years prior with eventual remission, but later recurred. Sxs included brain fog and mood disturbances. He achieved control with pasireotide but discontinued due to abnormal liver function tests. He was then treated with KCZ 400 mg/day but remained hypercortisolemic (LNSC 1.1x ULN) and was interested in trying a new medication, so was switched to LKCZ 150 mg BID with significant improvement of sxs and normalization of LNSC. Case 3: 54 yo F with presumed cyclic CD (negative whole-body and octreotide scans) with UFC 1.7x ULN and LNSC 3x ULN. TSS was performed with negative pathology; she had persistent hypercortisolemia and sxs including insomnia, fatigue, and mood disturbances. She was intolerant to and/or uncontrolled on 4 medications, including KCZ at 1000 mg/day that was discontinued due to a rash. She was started on LKCZ 150 mg BID and achieved normal LNSC and UFC after about 1 month. The drug was discontinued due to the development of a rash similar to that with KCZ. Conclusion: LKCZ is a new option for the treatment of CS in patients whose disease persists after TSS. These 3 patients had improvement of sxs and normalization of cortisol levels while on LKCZ, although one patient discontinued LKCZ due to a rash that was previously experienced with KCZ. The other two patients are being carefully monitored for liver function test elevation, QTc abnormalities and adrenal insufficiency with no issues to date. To our knowledge, this is the first case series of CS patients treated clinically with LKCZ. Presentation: 6/1/2024

8594 Pasireotide and Pasireotide Combined Treatment in Aggressive, Giant Pituitary Neuroendocrine Tumours

Abstract Disclosure: K. Ciszek: None. A. Bogusławska: None. M. Komisarz-Calik: None. J. Kunicki: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None. Pasireotide is a second-generation somatostatin analogue that gained recognition as a treatment option for acromegaly and Cushing disease. Recently, there are single reports of pasireotide treatment in other subtype of pituitary neuroendocrine tumours (PitNETs).We present a case series of aggressive, giant PitNETs which were treated with pasireotide alone or as combined multimodal treatment. Case 1: A 59-year-old male presented in our Unit due to severe headaches and visual field deficits. The patient underwent transsphenoidal surgery (TSS) ten years ago. Histopathology results showed partially acidophilic adenoma (FSH- LH- GH- ACTH- PRL-). Control MRI showed tumour regrowth - 56x56x89mm and invasion of local structures. The patient was qualified for radiotherapy, to which he did not consent. Due to the progression of symptoms, temozolomide and pasireotide were introduced. After 5 months, significant improvement in headaches and vision was observed. In MRI stable pituitary mass was noted. Case 2: A 17-year-old male presented in our clinic due to daily severe headaches and peripheral vision loss who underwent two non-radical surgeries for dopamine-resistant giant prolactinoma. In control MRIs progressing mass 38x34x33mm invading local structures was observed. Due to resistance to dopamine agonists and worsening of the symptoms, pasireotide was introduced resulting in a decrease of headaches and improvement in vision. The tumour size remained stationary. Case 3: A 59-year-old male presented with severe headaches and life threatening tumour mass effect.In MRI a 48x48x33mm mass was observed. The patient underwent two non-radical TSS, 4 cycles of pasireotide, and cyberknife treatment. Histopathology showed gonadotroph PitNET. MRI showed tumour shrinkage to 45x46x29mm, with persistent severe headaches. The patient was re-qualified for pasireotide treatment. Case 4: A 33-year-old male reported to the Clinic due to severe headaches and vomiting. In MRI pituitary mass 33x39x55mm and a cerebral oedema were revealed. TSS with external ventricular drainage was performed -histopathology results showed densely granulated silent corticotroph adenoma subtype 1, Ki67&amp;lt;1%. After 3 months, MRI showed tumour progression to 39x40x30mm. Two emergency TSS followed by stereotactic radiotherapy were performed. Combined therapy with pasireotide, cabergoline and temozolomide was introduced. After 18 months, stabilization of the disease was observed with the complete disappearance of headaches. Conclusions: Our study demonstrates the clinical potential of pasireotide treatment in aggressive, giant PitNETs. The therapy alone, or in combination has a potential role in reducing the tumour size, and allows the stabilization of the disease. The analgesic and anti-inflammatory effect of pasireotide could potentially alleviate headaches in this subset of patients. Presentation: 6/2/2024