Nonfunctioning Tumors Research Articles

CcfDNA analysis for the classification of adrenocortical adenomas.

Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies. We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants. Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples. Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.

A retrospective analysis of 338 surgically treated pituitary adenomas.

To summarize the clinical characteristics, pituitary function assessment, postoperative pathological features, and postoperative recurrence of surgically treated pituitary adenomas (PAs). We retrospectively reviewed the data of 338 patients (169 women; average age: 50.01 ± 12.47 years) who underwent surgical PA resection at our hospital during 2016-2020. Pathological PA classification was based on postoperative immunohistochemical staining for pituitary hormones. The clinical, imaging, laboratory, and follow-up data of the patients were statistically analyzed using SPSS v25.0. The main complaints of PA patients were compressive symptoms, followed by endocrine symptoms; 23 tumors were incidentalomas. Compared with the 93 patients with functioning PAs, the 245 patients with non-functioning PAs were older, and had greater tumor diameters and rates of cavernous sinus invasion and pituitary apoplexy (P < 0.05). Postoperative hormonal staining most commonly revealed ACTH (27.4%) and FSH/LH positivity (20.6%); 23.1% of non-functioning tumors stained negative for pituitary hormones. Preoperative anterior hypopituitarism commonly involved the gonadal and thyroid axes, and was correlated with male sex and tumor diameter (P < 0.05). The optimal cut-off for tumor diameter was 1.95 cm for predicting preoperative hypopituitarism in patients with non-functioning PAs. The number of operations and preoperative hypopituitarism were correlated with postoperative pituitary dysfunction (P < 0.05). In the non-functioning PA group, tumor diameter was a risk factor for postoperative recurrence (optimal cutoff: 2.75 cm). The management of patients with surgically treated PAs is limited by deficiencies in pathological classification, assessment of hypopituitarism, and detection of recurrence.

The diagnostic dilemma of adrenal vascular tumors: analysis of 21 cases and systematic review of the literature.

Adrenal vascular tumors are mainly represented by adrenal cavernous hemangiomas (ACHs) and adrenal cystic lymphangiomas (ACLs). Their radiological features often overlap with malignant tumors, therefore ruling out malignancy becomes mandatory. We analyzed clinical, radiological, and histopathological data to identify specific characteristics of these tumors. We reviewed 21 patients with ACHs (n = 12), ACLs (n = 8), or adrenal cysts (n = 1) confirmed by histopathology. We selected 82 papers from PubMed to provide a systematic review of the literature. In our cohort, median age at diagnosis was 58 years, with sex evenly distributed. All tumors were unilateral (median size = 44 mm), with 6 cases of increasing tumor size. All tumors exhibited non-contrast CT density > 10 Hounsfield Unit (HU). Calcifications were found in 5 cases. Hormonal studies revealed 11 non-functioning tumors and 2 cortisol-secreting tumors. Elevated urinary metanephrines were found in 2 cases. Immunostaining showed CD31/CD34/factor VIII expression in ACHs (n = 5, 24%) and podoplanin expression in ACLs (n = 6, 29%). The literature review revealed 71 reported cases of ACHs and 104 reported cases of ACLs. Median age at diagnosis was 46 years, with slightly female prevalence (63%). Median tumor size was 48 mm. 84 cases were symptomatic, with life-threatening hemorrhage reported in only 3 patients. Calcifications were found in 23% of cases. Surgical approaches varied, with open and laparoscopic adrenalectomy performed in 55 and 42 patients respectively. ACHs and ACLs represent a diagnostic dilemma in clinical practice due to their rarity and their misleading imaging features.

Endoscopic-Ultrasound-Guided Radiofrequency Ablation for Pancreatic Tumors.

Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) is a promising minimally invasive technique for the treatment of pancreatic lesions. This review first focuses on the technical aspects in EUS-RFA: the procedure typically employs EUS probes with integrated radiofrequency electrodes, enabling accurate targeting and ablation of pancreatic lesions. Different types of RFA devices, monopolar and bipolar energy delivery systems, are discussed, along with considerations for optimal ablation, including energy settings, procedure time, and pre- and post-procedural management. This paper presents a comprehensive literature review of EUS-RFA applied to both solid and cystic pancreatic lesions, including functioning and non-functioning pancreatic neuroendocrine tumors (pNETs), pancreatic cystic lesions (PCLs), pancreatic ductal adenocarcinoma (PDAC), and pancreatic metastases (PMs), discussing current evidence on safety, efficacy, clinical outcomes, and adverse events (AEs). EUS-RFA is an emerging technique with expanding potential for the treatment of both benign and malignant conditions; however, further studies are needed to better define patient selection criteria, assess long-term benefits, and establish definitive indications for its use.

Temozolomide treatment in refractory pituitary adenomas and pituitary carcinomas.

Temozolomide (TMZ), a non-classical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs). Systematic evaluations indicate a radiological response rate of 41% and a hormonal response rate of 53%, underscoring TMZ clinical efficacy, particularly when combined with radiotherapy. Functional tumors demonstrate a higher response rate compared to non-functional tumors. While the optimal duration of TMZ treatment remains undetermined, studies suggest that longer therapy durations may lead to better prognoses. Additionally, prior to TMZ administration, it is advisable to conduct immunohistochemical analysis of O6-methylguanine-DNA methyltransferase (MGMT), MSH2, MSH6, MLH1, PMS2, and N-methylpurine DNA glycosylase (MPG) to assess the potential impact of repair mechanisms such as direct repair (DR), mismatch repair pathway (MMR), and base excision repair (BER) on TMZ treatment. The efficacy of TMZ analogs, combined TMZ therapies, and TMZ with nanomaterials following TMZ treatment failure remains uncertain. The involvement of experienced multidisciplinary pituitary teams in all management decisions for RPAs/PCs patients is essential.

NON-FUNCTIONING SPORADIC PANCREATIC NEUROENDOCRINE TUMOR IS AN INDEPENDENT RISK FACTOR FOR RECURRENCE AFTER SURGICAL TREATMENT.

Pancreatic neuroendocrine tumors (PNETs) are uncommon and heterogeneous neoplasms, often exhibiting indolent biological behavior. Their incidence is rising, largely due to the widespread use of high-resolution imaging techniques, particularly influencing the diagnosis of sporadic non-functioning tumors, which account for up to 80% of cases. While surgical resection remains the only curative option, the impact of factors such as tumor grade, size, and type on prognosis and recurrence is still unclear. To investigate prognostic risk factors and outcomes in patients with sporadic PNETs treated surgically. A retrospective analysis was conducted on patients with sporadic PNETs who underwent pancreatic resection. Data were collected from medical records. A total of 113 patients were included: 32 with non-functioning tumors (NF-PNETs), 70 with insulinomas, and 11 with other functioning tumors (OF-PNETs). Patients with insulinoma were significantly younger, had a higher BMI, lower prevalence of comorbidities and ASA scores, and underwent significantly more pancreatic enucleations compared to patients with OF-PNET and NF-PNET. The insulinoma group had more grade I tumors, smaller tumor diameter, lower TNM staging, and lower disease recurrence rates. In univariate analysis, age, tumor type, tumor size, and TNM staging were identified as potential risk factors for tumor recurrence. In multivariate analysis, only the NF-PNET type was identified as an independent prognostic factor for disease recurrence. NF-PNETs are an independent prognostic risk factor for disease recurrence. This finding supports the need for closer follow-up of patients with small tumors who are selected for conservative management.

Factors affecting hormonal outcomes in patients undergoing surgery for non-functioning pituitary neuroendocrine tumors: a prospective observational study.

Surgical resection of non-functioning pituitary neuroendocrine tumors (NF-PitNET) is associated with new onset hormonal axis (HA) dysfunction, and factors predicting HA dysfunction are controversial, especially in large and giant NF-PitNET. Thus, we evaluated the postoperative hormonal function and assessed factors affecting HA dysfunction in patients with NF-PitNET. This prospective observational study involved 50 patients who underwent endoscopic surgical resection of NF-PitNET in the Department of Neurosurgery (April 2023-March 2024). The preoperative tumor diameter and volume were calculated radiologically. Hormonal evaluation was performed preoperatively, and again postoperatively at 7-days and 90-days. At 90-days, 36% patients recovered HA function, 34% remained unchanged, while 30% worsened. Serum cortisol (p < 0.0001), adrenocorticotropic hormone (p = 0.012), growth hormone (p = 0.013), and luteinizing hormone (p = 0.020) levels increased significantly; serum prolactin (p = 0.016) decreased significantly; while serum thyroid-stimulating hormone, follicle-stimulating hormone, and testosterone levels remained unchanged (all p > 0.05). Overall, there was no significant change in grade of HA dysfunction (p > 0.05). Male sex (OR:5.630, 95%CI:1.648-19.232; p = 0.006), tumor volume (OR:3.511, 95%CI:1.308-9.423; p = 0.013) and tumor diameter (OR:9.489, 95%CI:2.916-30.878; p < 0.0001) were significantly associated with postoperative HA dysfunction. Tumor volume and diameter (cut-off: 8.87 cm3 and 2.95cm, respectively) predicted postoperative HA dysfunction with a sensitivity of 96.0% and 92.0%, and a specificity of 88.0% and 76.0%, respectively. New-onset diabetes insipidus (30%) was the predominant complication. Tumor diameter and volume are significant predictors of postoperative HA dysfunction. More than one third of patients improved their HA function, while it worsened in less than a third of patients.

Predictors Based on the Radiologic Characteristics for Aggressiveness of Small (< 20 mm) Nonfunctioning Pancreatic Neuroendocrine Tumors.

To find the association between preoperative computed tomography (CT) features combined with tumor marker and known high-risk factors of small nonfunctioning pancreatic neuroendocrine tumors (NF-PNETS), thereby selecting appropriate treatment strategy for these patients. One hundred fourteen patients with NF-PNETs< 20 mm who underwent surgical operation were retrospectively analyzed from 2009 to 2023. Univariate and multivariable logistic regression analyses were performed to find the relationship between preoperative clinical psychological and CT features and high-risk factors. The overall survival (OS) rates with and without high-risk factors were compared. Of 114 patients, 29(25%) had at least one of these high-risk factors. Main pancreatic duct dilation (OR, 3.315; 95% CI, 1.079-10.184; p = 0.036), irregular tumor margin (OR, 2.955; 95% CI, 1.021-8.551; p = 0.046), positive tumor marker (OR, 6.047; 95% CI, 1.408-25.963; p = 0.015) were associated with increased odds of having any of these high-risk factors. The time to death differed significantly between patients with and without high-risk factors. Patients combining with high-risk factors were associated with lower 3- and 5-year OS (100% vs. 81.8%, 93.1% vs. 81.8%, respectively; p = 0.035 for both). Main pancreatic duct dilation, irregular tumor margin and positive tumor marker could screen a subset of patients recommended for surgery.

Differential proteomic expression in non-functional pituitary neuroendocrine tumours and pituitary glands.

Pituitary neuroendocrine tumours (PitNETs) are common accounting for 10 to 25 % of all intracranial tumours. This project describes the feasibility of developing a novel membrane-based biomarker that could be used for fluorescent guided surgery. The aim was to catalogue the differential expression of membrane proteins between non-functional PitNETs and pituitary glands. Ten pituitary gland tissue specimens were obtained from the National Institute of Health (NIH) NeuroBio-Bank and twenty non-functional PitNETs were obtained from the Northwestern University Nervous System Tumour Bank. Mass spectrometry analysis using an Orbitrap Fusion Lumos Tribrid Mass Spectrometer linked to a Dionex Ultimate 3000 UPLC system was undertaken. Data Dependent Acquisition Mass Spectrometry and Data Independent Acquisition Mass Spectrometry was then completed. Pathway enrichment analysis was performed using clusterProfiler v4.6.0. Functional enrichment analysis was conducted using Gene Ontology terms and Reactome pathways. Differential expression analysis between the two groups revealed a total of 2110 significant differently expressed proteins (DEPs), with 1387 of these also having a Log2 fold change either greater than 1, or less than -1. Of the 2110 DEPs, 925 were upregulated in tumours compared to control, while 1185 were downregulated. We have demonstrated a proteomic comparison between non-functional PitNETs and normal pituitary glands. These results demonstrate differences consistent with contemporary literature but shows that NOTCH3 and PTPRJ are up-regulated in non-functional PitNETs compared to pituitary glands.

Circulating Chromogranin A is associated with disease extent, progression and recurrence in patients with non-functioning pancreatic neuroendocrine tumor (NF-PNET).

Non-functioning Pancreatic Neuroendocrine Tumors (NF-PNET) are rare tumors with heterogeneous biology. Radiology and serum biomarkers are used for post-resection surveillance; however, no universally established protocol exists. Serum Chromogranin A (CgA) concentration is elevated in NF-PNET, and generally correlates with burden of disease; many CgA studies include mixed gastrointestinal and pancreatic populations. We sought to review the NF-PNET literature with focus on post-resection surveillance and hypothesized that CgA is useful for surveillance after NF-PNET resection. Comprehensive English literature review by PICO criteria (P-human NF-PNET patients; I-pancreatectomy; C- none; O- CgA correlation with disease recurrence). Four studies yielded granular data for resected NF-PNET patients. From 333 patients, 113 recurred and 110 (97%) had elevated CgA. Additional 7 studies with mixed gastro-entero-pancreatic NET included 269 NF-PNET patients. In these patients, CgA uniformly predicted disease extent. Serum Chromogranin A correlates with disease extent in NF-PNET, and is useful for surveillance after resection of NF-PNET.

Impact of Female Sex and Mild Cortisol Secretion on Coagulation Profile in Adrenal Incidentalomas.

Studies describing the coagulation profile in adrenal adenomas still need to be added. We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas. Cross-sectional study. From January 2019 until April 2023, participants in the Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations trial (NCT04127552) diagnosed with adrenal adenoma were categorised according to the 1 mg overnight dexamethasone-suppression test (1 mg-DST). Coagulation parameters were evaluated, and two-way ANOVA was used to elucidate the cortisol-by-sex interaction. Of 153 patients screened, 90 were enrolled (62.2% female, mean age 62 ± 10 years): 41 with non-functioning adrenal tumour (1 mg-DST ≤ 1.8 µg/dL), and 49 with a MACS (1 mg-DST > 1.8 µg/dL). Platelet counts were higher in the MACS group (P = .01). Regression analysis identified female sex (B = 36.603, P = .011), 1mg-DST (B = 0.238, P = .042), and younger age (B = -1.452, P = .038) as independent predictors for elevated platelet count. In patients with MACS, women exhibited higher levels of procoagulant factors fibrinogen (P = .004) and factor VIII (P < .001), and coagulation inhibitors protein C (P = .003) and antithrombin III (P = .005) than males. No differences were observed in the non-functioning adrenal tumour group, providing a cortisol-by-sex interaction regarding fibrinogen (P = .047), factor VIII (P = .046), and protein C (P = .028). Our findings revealed a worse coagulation profile in women with MACS, underscoring the need for a sex-specific approach in clinical practice to manage thrombotic risks effectively. Dedicated prospective studies are needed to validate and integrate these findings into clinical strategies for thromboprophylaxis.

Radiation therapy in functioning and no functioning pituitary neuroendocrine tumor: systematic review of the recent literature after 2011.

Neuroendocrine pituitary tumor, a benign cells proliferation, can cause significant morbidity due to its local invasiveness and secretory properties. Historically, radiotherapy has been employed as a second or third-line treatment option, with studies dating back to the mid-20th century. However, advancements in radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery, and proton therapy, have revolutionized treatment approaches. This review aims to critically evaluate the recent literature (2011-2022) on the use of radiotherapy in both functioning and nonfunctioning neuroendocrine pituitary tumor. We employed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology to systematically analyze 52 articles, focusing on local and hormonal control, radiotherapy protocols, and treatment-related side effects.

Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model.

PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2cm). Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.

A Single Center Experience of Special Cases: Isolated Adrenal Myelolipoma and Adrenocortical Adenoma with Myelolipomatous Component.

Isolated adrenal myelolipoma (IAM) is an uncommon, nonfunctioning tumour of the adrenal gland, primarily composed of adipose tissue and hematopoietic trilinear cells. The etiopathogenesis and clinical relevance of this neoplasm remain poorly understood. However, similar myelolipomatous alterations can also occur within adrenocortical adenomas. This report presents our findings on IAM and adrenocortical adenomas with a myelolipomatous component (AMC), focusing on comparing these cases' clinical, demographic, and pathological characteristics. Data from twenty patients were retrospectively analyzed, including twelve diagnosed with IAM and eight with AMC, all of whom underwent adrenalectomy. In the IAM cohort, surgical intervention was primarily indicated based on tumour size and/or related symptoms, while in AMC cases, the indication was often driven by hormonal activity. Patients with IAM had an average age of 52.5 years, with a predominance of female patients (75%). A significant proportion of this group was obese, with concomitant hypertension (HT) and/or type 2 diabetes mellitus (DM). The tumours were predominantly right-sided, with a median size of 69.0 ± 40.0 mm. Notably, 58% of patients with IAM presented with flank or abdominal pain attributed to the mass effect. None of the IAM cases exhibited hormonal activity. Conversely, the AMC group had a younger average age of 46 years, with a high prevalence also in female patients (63%). The tumours were generally smaller, with a median size of 40.0 ± 16.0 mm, and were mostly left-sided. All patients in this group had a history of HT and/or DM, with six exhibiting hormonally active tumours, which manifested as various clinical syndromes, including Cushing syndrome, pheochromocytoma, and Conn syndrome. While IAM and AMC share several common features, they also demonstrate distinct differences. The presence of endocrinological syndromes was more frequent in AMC cases, whereas IAM cases rarely showed hormonal activity. The most pronounced difference between the two groups was the tumour size at diagnosis, which contributed to the varying clinical presentations upon hospital admission. Furthermore, the high prevalence of obesity, HT, and DM in both groups suggests that these comorbidities may play a role in the development of myelolipomatous patterns observed in these tumours.

Sinonasal Outcomes after Endoscopic Pituitary Surgery in Patients With Cushing's Disease.

The endoscopic endonasal approach (EEA) has become the preferred treatment for pituitary tumors, with minimal sinonasal morbidity. However, patients with Cushing's disease (CD) may represent a subgroup with prolonged impairment of sinonasal quality of life (QOL). We retrospectively identified patients with CD who underwent EEA at our institution. Control patients with non-functional tumors were matched by age, gender, and extent of EEA. The primary outcome was post-operative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Ten patients with CD met the selection criteria and 20 controls were selected for comparison. Nine of the CD patients achieved persistent endocrinologic remission post-operatively. Comparing the CD and control groups, there was no difference in post-operative SNOT-22 score at 1 or 3 months. At 6 months, SNOT-22 scores were significantly worse in the CD group (27.4 ± 21.6 vs. 2.8 ± 2.3, P = .039). SNOT-22 scores improved to normal from 1 to 6 months in the control cohort (P = .007), but not in the Cushing's group (P = .726). Morbidity was present across all SNOT-22 domains, but was highest in the sleep domain (P = .023). Only morbidity in the facial domain improved over time (P = .032). Patients with CD have significantly prolonged postoperative sinonasal QOL impairment following EEA compared to patients with non-functioning tumors, who normalize within 6 months. In CD patients, only morbidity in the facial domain, likely related to post-operative pain and nasal packing, improved over time, while the sleep domain was the most affected.

Immunohistochemical expression of CYP11A1, CYP11B, CYP17, and HSD3B2 in functional and nonfunctional canine adrenocortical tumors.

Functionality of human adrenal tumors is inferred by CYP11B1 (cortisol synthase) expression, CYP11B2 (aldosterone synthase) expression, or both. Nonfunctional canine adrenal tumors have low expression of steroidogenic enzymes, whereas aldosterone-producing tumors express CYP11B, and cortisol-producing tumors express both CYP11B and CYP17. Twenty-two client-owned dogs with adrenocortical tumors (ACT) (8 nonfunctional, 7-cortisol producing, 2 aldosterone-producing and 5 functional noncortisol producing) and 2 dogs with normal adrenal glands. Retrospective case series. Adrenal functionality was determined from clinical signs and endocrine testing. CYP11A1, CYP11B, CYP17, and HSD3B2 expression was detected by immunohistochemistry on formalin-fixed paraffin-embedded adrenal tissue. Protein expression was semiquantified by 2 blinded observers using H-scoring (results reported as median [range]) and compared in nonfunctional and cortisol-producing adrenal tumors by Mann-Whitney U tests. CYP11A1, CYP11B, and HSD3B2 were present within all cortical layers of normal adrenal glands, and CYP17 was expressed within the zona fasciculata and zona reticularis. Expression of CYP11A1 (191.25 [97.5-270] vs. 175 [102.5-295] P = .69), CYP11B (190 [130-265] vs. 147.5 [95-202.5]; P = .07), CYP17 (177.5 [87.5-240] vs. 247.5 [55-292.5]; P = .40), and HSD3B2 (230 [47.5-295] vs. 277.5 [67.5-295]; P = .34) were not significantly different between cortisol-producing and nonfunctional ACT. Our findings suggest it is not possible to determine functionality of canine ACT by immunohistochemistry for steroidogenic enzymes. Tumor size cannot be used to infer functionality of adrenal tumors.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

8801 Towards Safe and Efficacious Medical Therapy for Patients with Clinically Non-Functioning Pituitary Tumors

Abstract Disclosure: D. Zhang: None. M. Bergsneider: None. W. Kim: None. M.B. Wang: None. H. Vinters: None. A.P. Heaney: None. Clinically non-functioning pituitary tumors (CNFTs) account for one-third of all pituitary adenomas. They do not cause clinical and/or biochemical evidence of tumor-related hormone hypersecretion, grow insidiously and typically present with mass effect symptoms such as headache and visual field deficits. Surgical resection is the current standard of care for CNFTs but complete resection is infrequently achieved due to their size and invariable invasion of locally adjacent structures. CNFT remnant tumor regrowth rates approach 50% and these patients may need repeat surgery and/or radiotherapy (RT). The latter is quite effective in achieving tumor control, but carries a risk of hypopituitarism of ∼ 40% at 10 years. Although dopamine agonists and somatostatin receptor ligands have been explored as medical therapy, there are currently no consistently effective medical treatments for CNFTs. There is a clear unmet need for novel safe and effective medical therapies for these comparatively common tumors. In a highly innovative approach we have used patient-derived ex vivo 3D tumoroid human CNFTs in an automated high throughput compound screen (HTS) to identify novel tumoricidal and growth inhibitory compounds for CNFTs. To date, we have screened ∼4,000 compounds and have identified 13 potential hits that inhibited tumor cell proliferation (a reduction of 76±15%) and induced apoptosis (induction rate of 8.2 ± 6.6) in the CNFT tumoroids respectively. The hit compounds to date fall into 3 categories based on their targets, namely Na+/K+-ATPase inhibitors (n=6), reactive oxygen species (ROS) regulators (n=4), and cell cycle inhibitors (n=3). Representative “hit” compounds from each group identified in our primary screen were rescreened in triplicate in 20 concentrations from 25µM to 50pM at 2-fold dilutions. Dose-response curves characterized compound doses that inhibited cell viability by 50% (IC50) and ranged from 13nM to 103nM. Two of these 3 compounds also induced 2-3-fold apoptosis at 0.1uM with the final compound displaying a potent 5-10-fold pro-apoptotic effect at 0.15uM concentration. In parallel, we used single cell RNA sequencing to validate targets that emerged from our HTS and to characterize the mechanism of action (MOA) of these hit compounds. As proof of concept, several of the known drug targets were noted to be amongst the highest differentially expressed genes in the CNFT tumor cell population. This approach validating a candidate target in conjunction with demonstrable activity of a drug for that same target in CNFTs may simultaneously provide us with a back-bone molecule to further develop with structural activity relationship analysis and/or allow us to individualize drug choice in patients based on immunocytochemical tumor target expression. Presentation: 6/1/2024

6743 Decline in IGF-1 after surgery of the nonfunctioning pituitary neuroendocrine tumor

Abstract Disclosure: J. Sugata: None. S. Fujio: None. R. Makino: None. T. Hanada: None. R. Hanaya: None. Background: Patients undergoing surgical treatment for nonfunctioning pituitary neuroendocrine tumors (PitNET) may experience impaired secretion of growth hormone (GH). The optimal timing for assessing GH secretory function postoperatively remains unclear. In our department, we typically conduct hormone-loading tests three months after surgery. However, even in some cases without a diagnosis of growth hormone deficiency (GHD) at that point, there might be a gradual decline in Insulin-like growth factor-1 (IGF-1). Methods: We studied patients who exhibited peak GH levels &amp;gt; 1.8ng/ml in an insulin tolerance test (ITT) three months after undergoing surgery for nonfunctioning PitNET. We evaluated the levels of IGF-1 during the last observation, excluding cases where reoperation or radiosurgery was performed. Results: We identified 67 cases (29 males, 38 females) meeting the study criteria, with a median age of 54 years. The median follow-up time spanned 6 years (range 1-13 years). The median standard deviation (SD) scores of IGF-1 three months after surgery were -0.96, with 14 cases (21%) below -2.0 SD. At the end of the follow-up period, the median SD scores of IGF-1 were -1.31. This was significantly lower than the three-month time point (p&amp;lt;0.01), and 21 cases (31%) recorded were below -2.0 SD. In 6 cases suspected of severe GHD due to subjective symptoms or decreased IGF-1, ITT, or GH-releasing peptide-2 were retested. Among these, 2 cases were diagnosed with severe GHD, while the remaining demonstrated normal secretion of GH despite the low concentration of IGF-1. The IGF-1 SD scores at the end of follow-up and the three-month time-point exhibited a significant correlation (R2=0.74, p&amp;lt;0.01). However, no correlation was found between IGF-1 scores and peak GH concentration, age, tumor size, pituitary apoplexy, or preoperative IGF-1 SD scores. Conclusions: IGF-1 exhibited a progressive decrease in the majority of cases without severe GHD, with some cases showing reductions greater than -2.0 SD. Our findings emphasize the importance of cases with long-term clinical follow-up low IGF-1 after PitNET surgery, even when GH secretion appears normal. Presentation: 6/1/2024

7446 Primary Adrenal Mature Teratoma Initially Diagnosed As An Adrenal Myelolipoma

Abstract Disclosure: A. White-Cotsmire: None. B. Kodali: None. A.M. Avram: None. S.S. Shah: None. Background: Teratomas are a type of germ cell tumor containing different types of tissue (e.g., hair, teeth, bone adipose, muscle). Most teratomas are benign (i.e., mature), but they may also be malignant (i.e., immature). Both immature and mature teratomas contain derivatives of ectoderm, endoderm, and mesoderm; however, immature teratomas are differentiated by the presence of embryonic, usually neuroectodermal, tissue. Mature teratomas have the potential for malignant transformation (1–2% of cases), usually squamous cell carcinoma within the teratoma. Extra-gonadal teratomas are rare (only 1–5%); reported locations include sacrococcygeal, head and neck, retroperitoneum, mediastinum, brain and spine, liver, and rarely adrenal glands. (1) Only 18 cases of adult primary adrenal teratomas have been reported since 1952. (2)Clinical Case: A 48-year-old woman with 4 days of worsening abdominal pain underwent CT imaging, which demonstrated a 6cm complex left adrenal mass containing peripheral and scattered internal-coarse calcifications with internal soft tissue and fat components, suggestive of adrenal myelolipoma with probable sequela of previous hemorrhage. Subsequent endocrine follow-up ruled out a cortisol secreting tumor with a negative dexamethasone suppression test and pheochromocytoma with normal serum free metanephrines and normetanephrines. Dedicated adrenal protocol CT scan further characterized the mass as a mature adrenal teratoma containing a rudimentary mandible and two teeth within the soft tissue associated with internal microscopic fat. The left renal vein was anteriorly displaced by this left adrenal mass and severely narrowed by the large adrenal mass, with development of left retroperitoneal collateral venous drainage from the left kidney into the lumbar venous system. The patient opted for conservative management with active clinical surveillance. Conclusion: This is a rare case of adrenal mature teratoma in an adult, originally diagnosed as an adrenal myelolipoma. This case highlights the use of more dedicated adrenal imaging for the characterization of adrenal tumors and the broad differential of benign non-functional adrenal tumors, including myelolipomas, lipomas, angiomyolipomas, and nonfunctional adenomas. However, a definitive diagnosis can only be confirmed by surgical removal of the tumor, usually through a laparoscopic approach, with histopathologic evaluation.