BACKGROUND:Duodenopancreatic neuroendocrine tumors (dpNETs) are a frequent manifestation in patients with MEN type 1 (MEN1), and metastatic dpNETs are the primary cause of mortality. We evaluated a humoral response in the form of immunoglobulin (Ig)-bound antigens that are associated with dpNET development and progression in patients with MEN1. STUDY DESIGN:Proteomic analysis of plasma Ig-bound proteins was performed in a cohort of 42 MEN1 patients with dpNET (28 with indolent disease and 14 with liver metastasis) and 14 MEN1 patients without dpNETs. Ingenuity Pathway Analysis and major histocompatibility complex class II binding prediction (NetMHCIIpan) were performed to identify candidate immunogenic antigens and underlying networks. Findings were further compared with proteomics profiles of human pNET tissues. RESULTS:A total of 1,117 Ig-bound proteins were identified. Differential analyses revealed 435 Ig-bound antigens to be enriched (exclusive or fold change 2 or higher) in dpNET patients compared with MEN1 patients without dpNETs, of which 130 were highest in those with a dpNET and liver metastasis. Ingenuity Pathway Analysis of the 435 dpNET-associated Ig-bound antigens revealed cancer, endocrine system disorders, and neurological disease as top predicted disease types, and networks centered on B-cell receptor and T-cell receptor signaling as well as TP53 and transforming growth factor-beta signaling. An intersection of proteomic profiles from human MEN1 pNET tissues revealed 73 overlapping proteins. major histocompatibility complex-II affinity prediction identified SF3B3, ADD2, MDM2, INTS4, and CMTM1 to encompass high-binding immunocore sequences. CONCLUSIONS:We have uncovered antigenic protein signatures in the form of a humoral response associated with the development and progression of MEN1-related dpNETs.

Heritable thyroid tumors represent a clinically important subset of endocrine neoplasms, accounting for approximately 3-9% of well-differentiated thyroid cancers and 25% of medullary thyroid cancers. In patients presenting with a new thyroid malignancy, recognition of an underlying hereditary cancer predisposition syndrome has important implications for management, surveillance for associated malignancies, and testing of at-risk relatives. This review summarizes the epidemiology, clinical presentation, histopathologic features, management, and surveillance recommendations for hereditary thyroid tumors in the setting of familial non-medullary thyroid cancer, multiple endocrine neoplasia type 2, familial adenomatous polyposis, Cowden syndrome, Li-Fraumeni syndrome, DICER1 syndrome, CHEK2-related cancer predisposition, and Carney complex. In the future, continued research is needed to better understand genotype-phenotype correlations, optimize surveillance strategies, and improve risk stratification to enable more personalized care for patients and families affected by these conditions.

Background A thyroid lobectomy is a commonly indicated procedure for a wide variety of thyroid pathologies; however, the decisions between a total thyroidectomy vs a lobectomy requires counseling of lifelong dependence on thyroid hormone supplementation. However, the need for thyroid supplementation following lobectomy can vary significantly among patients. This study aims to evaluate whether preoperative Thyroid-Stimulating Hormone (TSH) levels can help predict the requirement for thyroid hormone replacement therapy (THRT) postoperatively in patients undergoing thyroid lobectomy. Methods 1281 patients who received thyroid lobectomies for benign and malignant disease at MD Anderson Cancer Center from 2016 to February 2024 were screened. The exclusion criteria were a hyperactive nodule, undifferentiated thyroid carcinoma, age <18 years-old, no follow up at 6 months, and preoperative hypothyroidism. Post-operative TSH values were obtained early in the post-op period (6-8 weeks) and late in the post-op period (6-12 months). The primary outcome was the requirement for THRT at their follow up at 6-12 months post-op, using logistic regression analysis and ROC curve analysis to evaluate the predictive value of preoperative TSH levels. Results Of the 1281 patients screened, 200 met the inclusion criteria with a gender distribution of distribution of 74.37% female and 25.63% male with a median age of 50 ranging from 18 to 86 years old. Preoperative TSH levels varied among patients. Logistic regression analysis demonstrated that pre-op TSH levels were a significant predictor of the need for levothyroxine supplementation at 6-12 months post-op (Odds Ratio [OR] = 3.65, 95% Confidence Interval [CI] = 2.25-5.93, P < 0.001). Higher preoperative TSH levels increased the risk of needing THRT in the postoperative setting. Early post-op TSH (6-8 weeks post-op) (OR = 2.00, 95% CI = 1.48-2.70, P < 0.001) and late post-op TSH (6-12 months post-op) (OR = 1.21, 95% CI = 1.04-1.41, P = 0.016) were also significant predictors.A pre-op TSH cut-off value of 1.5 mIU/L was identified as the optimal threshold, with sensitivity and specificity at this cut-off being 66% and 75%, respectively. The Negative Predictive Value (NPV) was 63.5 while the Positive Predictive Value (PPV) was 76.8%. Conclusion The study demonstrates a significant correlation between preoperative TSH levels and the necessity for postoperative thyroid hormone supplementation. Patients with preoperative TSH levels above 1.5 mIU/L were more likely to require THRT at 6-12 months. These findings suggest that preoperative TSH could serve as a predictive marker for post-op thyroid function, aiding in preoperative patient counseling and management planning. This information is crucial for better counseling patients on the potential outcomes of thyroid lobectomy versus total thyroidectomy, helping them make informed decisions regarding their surgical options.

BACKGROUND:Postsurgical hypoparathyroidism (HypoPT) accounts for ∼75% of all HypoPT cases. It is recognized that this condition is largely preventable. Several studies have identified risk factors increasing the risk of developing postsurgical HypoPT, including patient-related factors, surgical factors, and, in some studies, presurgical factors. This narrative review highlights evidence-based guidelines for postsurgical HypoPT and provides strategies for its prevention, diagnosis, and management. METHODS:We searched PubMed, Embase, Google Scholar, and the Cochrane Library from inception through December 2025. We included studies that examined the definition, diagnosis, prevalence, risk factors, management, long-term complications, and treatment outcomes of postsurgical HypoPT. RESULTS:This review outlines strategies for identifying individuals at risk of developing postsurgical HypoPT, with the goal of minimizing these risks and using evidence-based approaches to accurately diagnose and effectively manage these patients. Historically, management of postsurgical HypoPT beyond the first 72 hours relied on calcium supplements with active vitamin D, which remains the first-line therapy in current practice. Parathyroid hormone (PTH) replacement has emerged as an option for individuals who do not respond to conventional therapy. More recently, a long-acting PTH molecule, palopegteriparatide, has been approved by the Food and Drug Administration for the management of HypoPT. This molecule has a 60-hour half-life and has demonstrated the ability to maintain normal serum calcium levels, lower urine calcium, lower serum phosphorus, and reduce the need for calcium and active vitamin D supplements. It has also demonstrated a positive impact on quality of life. Post hoc data from the phase 3 trial comparing palopegteriparatide with placebo demonstrated improvements in renal function with palopegteriparatide and cessation of conventional therapy in patients with HypoPT. CONCLUSIONS:Postsurgical HypoPT remains a significant complication of thyroid surgery; however, its risk can be mitigated by careful preoperative assessment and surgical technique. While conventional therapy continues to be the mainstay of treatment, the advent of PTH replacement therapies offers promising alternatives for patients with refractory HypoPT.

This review highlights recent advances in adrenal endocrine surgery and oncology, emphasizing progress in pathology, imaging, perioperative planning, and systemic therapy. In pathology, the World Health Organization recently refined the classifications of adrenocortical lesions as well as pheochromocytomas and paragangliomas. In radiology, new molecular imaging tracers and theranostics have advanced adrenal functional imaging. Novel applications of artificial intelligence and 3D anatomical modeling have also aided tumor diagnosis and adrenal surgery preoperative planning. In endocrine oncology, the expansion of tumor molecular profiling and the application of new targeted therapies has improved progression-free survival in patients with advanced pheochromocytomas and paragangliomas. Dual immunotherapy has modestly improved progression-free survival in patients with adrenocortical carcinoma. Recent changes in pathologic classification, imaging analysis, and novel applications of targeted systemic therapies have transformed care of patients with adrenal tumors, shepherding surgical and endocrine oncology into an era of precision medicine.

PURPOSE Survivorship care models that extend beyond recurrence surveillance to ones that also address treatment-related symptoms are needed. Using data obtained in routine clinical care, we aimed to examine patient-reported symptom burden among adult thyroid cancer survivors. METHODS Between September 2019 and September 2022, adults were electronically administered the MDASI-Thy, a patient-reported outcome measure that measures symptom severity and interference, within 7 days before their visit at a dedicated thyroid cancer survivorship clinic. The MDASI-Thy generates (1) core symptom severity, (2) thyroid-specific symptom severity, and (3) symptom interference scores, where lower is better. High alert values (HAVs) were defined for four symptoms: Distress (Upset), Pain, Sad, and Shortness of Breath. Multivariable generalized linear models examined associations of patient, cancer, and treatment factors with scores and any HAV. RESULTS Among 1,557 thyroid cancer survivors, 864 (55.5%) responded. Respondents were a median of 5 years from diagnosis (IQR, 4-8) and predominantly female (79.1%), and most had papillary thyroid carcinoma (92.5%). Mean (standard deviation) scores were 1.20 (1.34) for core severity, 0.99 (1.26) for thyroid-specific severity, and 1.07 (1.80) for interference. Fatigue (11.5%) and Disturbed Sleep (11.3%) were the most common severe symptoms. HAVs occurred in 72 survivors (8.3%), of whom 54 (75%) had a documented plan addressing the HAV. Higher symptom burden was associated with female sex, Black race, greater comorbidity, active smoking, and total thyroidectomy. CONCLUSION Routine patient-reported symptom screening in thyroid cancer survivorship identified generally low symptom burden but meaningful variations, with a subset reporting severe symptoms, functional interference, and HAVs requiring action.

Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant disorder that predisposes individuals to endocrine tumours, including pancreatic neuroendocrine tumours (PNETs), which range from indolent to metastatic. Liver metastases occur in up to 80% of high-grade and 30% of low-grade well-differentiated PNETs, contributing significantly to mortality. Predicting metastatic progression is critical for timely surgical intervention, yet clinical tools for such predictions remain inadequate. This study develops a radiomics-based model using contrast-enhanced CT scans to stratify outcomes in MEN1 patients. Patients were divided into two groups: PNET without liver metastases within 23 years (group 1; n=11) and PNET with liver metastases (group 2; n=5). The mean age of MEN1 diagnosis was 35±19 years for group 1 and 37±9 years for group 2. A total of 120 CT scans were analysed (85 from group 1 and 35 from group 2). Radiomic features were extracted from segmented liver and pancreas volumes to capture tumour-associated textural and spatial characteristics. Feature selection reduced the dataset to 57 key features, which were used to train a Random Forest classifier for robust prediction. The model achieved a cross-validated accuracy of 0.862 ± 0.062 and an AUC score of 0.927 ± 0.063 across 500 iterations, demonstrating reliable prediction of metastatic outcomes. Radiomics-based analysis of CT imaging offers a promising non-invasive approach for prognostic evaluation in MEN1 patients. This method could improve early risk stratification and support personalized management to mitigate metastatic progression.

Background Primary hyperparathyroidism is often caused by parathyroid adenomas (PAs), which can be ectopic (EPAs) or intrathyroidal (ITPAs). Accurate localization is crucial for effective surgical intervention. This study aimed to determine the detection rate of four-dimensional multidetector computed tomography (4D-MDCT), ultrasonography (US), and technetium 99 m sestamibi scintigraphy (MIBI) in detecting EPAs and ITPAs. Additionally, we explored the role of ultrasound-guided fine-needle aspiration (US-FNA) and evaluated correlations between parathyroid hormone (PTH) levels, adenoma size, and detection performance. Methods We retrospectively reviewed the records of 28 patients with 29 EPAs and 27 patients with 27 ITPAs who underwent 4D-MDCT, US (including cine Doppler US and US-FNA), and/or MIBI at our institution. Data were collected on demographics, laboratory values, imaging findings, and intraoperative findings. The detection rate was calculated for each imaging modality and their combination. Logistic regression models were used to assess the relationship between PTH level, adenoma size, and detection performance. Results The detection rate of EPAs was 96% for 4D-MDCT, 97% for MIBI, and 46% for US. The detection rate of ITPAs was 96% for US, 65% for 4D-MDCT, and 58% for MIBI. Combined multimodality imaging with results concordant between two or more modalities achieved an overall detection rate of 87%. For ITPAs, smaller PA size was associated with significantly worse MIBI detection performance (p < 0.05). The PTH level was not associated with detection performance. Conclusions Our study highlights the superior detection rate of 4D-MDCT and MIBI for EPAs and US for ITPAs. Combining imaging modalities enhances the diagnostic detection rate.

Background Hypoparathyroidism (HypoPT) is characterized by low serum calcium due to insufficient parathyroid hormone (PTH). This manuscript builds upon the 2022 international HypoPT guidelines and three systematic reviews, which have been further informed by updated narrative reviews and expert consensus. This paper presents current best practice consensus recommendations for the diagnosis and management of HypoPT. Methods An International Panel of Experts updated the previous systematic reviews (SR's), conducted narrative reviews, developed, and subsequently approved these best practice recommendations at the Parathyroid Summit, held as a pre-Endocrine Society meeting in May 2024 (Boston, USA). Results Diagnostic criteria for chronic HypoPT require hypocalcemia with inappropriately normal or low PTH levels. Conventional therapy is recommended as first line therapy and includes calcium supplementation, active vitamin D, correction of vitamin D inadequacy and correction of abnormalities in serum magnesium. Monitoring is required to achieve optimal serum calcium while avoiding hyperphosphatemia, hypercalciuria and declines in renal function. Assessment of HypoPT complications is required including skeletal health assessment in postmenopausal women and men over the age of 50 years. Specific strategies are provided for managing HypoPT during pregnancy and lactation as well as in children. PTH replacement with palopegteriparatide has been approved and is an important therapeutic option, especially when conventional therapy is inadequate or not tolerated. Conclusion These best practice recommendations provide a framework for HypoPT diagnosis and management, emphasizing individualized care, role of DNA analysis in the diagnosis of nonsurgical HypoPT, and role of PTH or PTH analogue therapy as appropriate. They complement the 2022 international guidelines and incorporate updated therapeutic recommendations from the past 3 years including the positioning of the newly approved molecule palopegteriparatide based on recent clinical trial data and expert consensus.

BACKGROUND:Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported. METHODS:Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024. RESULTS:One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and transmandibular (1%) approaches. Median RPLN metastasis size was 1.7 cm (interquartile range: 1.3-2.2) at surgery. Three months post-operatively, 11% had dysphagia and 1% had velopharyngeal insufficiency. Nonsurgical treatments included radioactive iodine (10%), radiation therapy (11%), and systemic targeted therapy (79%). CONCLUSION:RPLN metastases grow slowly, and those ≥ 1 cm typically undergo surgical resection without significant long-term morbidity.

Multiple endocrine neoplasia type 1 (MEN1) is characterised by combined occurrence of parathyroid tumours, duodenopancreatic neuroendocrine tumours, and anterior pituitary adenomas. Some patients might also develop thymic and bronchopulmonary neuroendocrine tumours, and adrenal tumours. MEN1 is an autosomal dominant disorder caused by mutations in the tumour-suppressor gene MEN1, which encodes a scaffold protein, menin. Without treatment, patients with MEN1 have high morbidity and premature mortality, which can be mitigated by early tumour detection and intervention. Identification of individuals at high risk for MEN1 can be facilitated by genetic testing of patients and their first-degree relatives, and undertaking periodic clinical, biochemical, and radiological screening in patients and MEN1 mutation carriers. However, no consensus exists regarding the optimal assessment and management of MEN1. To provide such recommendations, a multidisciplinary group was convened to undertake systematic reviews and a meta-analysis of the literature, and to use a Delphi approach for the development of consensus statements. 55 clinical recommendations were developed to guide clinicians, patients, and stakeholders about approaches for MEN1 in adults and children.

BACKGROUND:Pathway-driven, postpancreatectomy opioid reduction interventions have proven effective and sustainable and may have a "halo effect" on other major abdominal cancer operations. This study aimed to analyze the sequential effects of expanding opioid reduction efforts from pancreatectomy on opioids prescribed after hepatectomy. STUDY DESIGN:This was a retrospective cohort study using data from the electronic health record and a prospective quality improvement database for consecutive hepatectomy patients (September 2016 to February 2024). Cohorts were based on 5 distinct eras of opioid-related protocol updates E1 (preintervention historical baseline): September 2016 to March 2017; E2 (introduction of 5x-multiplier): April 2017 to September 2018; E3 (departmental opioid education program): October 2018 to December 2019; E4 (initial posthepatectomy pathways): January 2020 to June 2022; and E5 (updated pancreatectomy pathways influencing hepatectomy care): July 2022 to February 2024). RESULTS:Of 2,005 patients, 31% underwent major hepatectomy, 14% intermediate, 46% minor, and 9% combination surgery/other. Most (79%) patients were performed via an open approach. The median hospital stay decreased from 5 to 4 days between E1 and E5. Both intraoperative (E1, 80 mg; E5, 37 mg; p < 0.001) and total inpatient (E1 181 mg, E5 86 mg; p < 0.001) median oral morphine equivalents were reduced by >50%. A 73% reduction in discharge oral morphine equivalents was observed between E1 (225 mg) and E5 (60 mg; p < 0.001), with clinically similar median pain scores at discharge (scores 1 to 2 of 10). Concurrent universal adoption of routine 3-drug nonopioid discharge prescriptions (E1 70%, E5 98%) correlated with the proportion of patients discharged opioid-free (E1 8%, E5 43%; p < 0.001). CONCLUSIONS:Directed opioid reduction efforts for pancreatectomy influenced clinically meaningful posthepatectomy reductions in inpatient and discharge opioid volumes. A "halo effect" of intradepartmental opioid reduction efforts is attainable and corresponds to measurable increases in opioid-free or nearly opioid-free discharges after major abdominal cancer surgery.

Medullary thyroid carcinoma is a rare neuroendocrine tumor originating from calcitonin-secreting parafollicular C cells of the thyroid gland. Approximately 25% of cases in adults are hereditary medullary thyroid carcinoma (hMTC), arising from activating, germline pathogenic variants in the REarranged during Transfection (RET) proto-oncogene and causing the syndromes multiple endocrine neoplasia (MEN) types 2A and 2B. A paradigmatic feature of MEN2 is its robust genotype-phenotype correlations, which predict the disease spectrum and age of onset of hMTC and other clinical manifestations. Advances in genetic testing and systemic therapies and an improved understanding of the natural course of MEN2 have transformed the clinical presentation of hMTC from advanced-stage disease to early detection in asymptomatic RET pathogenic variant carriers. The management of hMTC has similarly evolved from aggressive, one-size-fits-all surgical approaches to personalized strategies informed by genotype, biochemical markers, and imaging findings. Risk-reducing early thyroidectomy remains the cornerstone of metastatic hMTC prevention, with the timing of surgery tailored to the specific pathogenic variant and clinical context. Additionally, recent advances in targeted systemic therapies offer promising options for patients with recurrent and/or metastatic disease. This "Approach to the Patient" article explores the diagnostic evaluation, surgical decision-making, systemic treatment options, and follow-up of patients with hMTC, emphasizing the critical role of multidisciplinary care in optimizing outcomes for patients and their families.

Metastatic duodenopancreatic neuroendocrine tumors (dpNETs) are the primary cause of mortality among patients with Multiple Endocrine Neoplasia Type 1 (MEN1). Emerging evidence implicates the microbiome and microbial-derived secreted factors in promoting cancer development and progression. In the current study, we report that circulating microbial-associated uremic toxins trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), cresol sulfate (CS), cresol glucuronide (CG), and phenol sulfate (PS) are elevated in MEN1 patients with metastatic dpNETs. Proteomic and metabolomic-based analysis of resected dpNET tissues from MEN1 patients revealed detectable levels of uremic toxins that positively correlated with peptide-based signatures corresponding to Faecalibacterium prausnitzii, Faecalibacterium nucleatum, and Klebsiella pneumoniae and negatively correlated with Streptococcus pneumoniae and Streptococcus thermophilus. A microbial-associated uremic toxin panel (MUTP) was developed and the panel yielded an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.85-1.00) with 67% sensitivity at 95% specificity for identifying MEN1 patients with metastatic dpNETS in an independent validation cohort. Increases in circulating microbial-associated uremic toxins during early stages of neoplasia were also found to be associated with poor overall survival in a Men1fl/flPdx1-CreTg mouse model of MEN1 pancreatic neuroendocrine tumors. Our findings suggest that microbial dysbiosis is associated with disease aggressiveness and that increases in circulating microbial-associated uremic toxins may identify individuals who are at risk of having metastatic dpNETs to better guide clinical management and intervention. Riccardo Ballarò, Amanda R. Wasylishen, Carolina R. Pieterman, Courtney Olsen, Ehsan Irajizad, Ranran Wu, Hiroyuki Katayama, Huiling Liu, Yining Cai, Jennifer Dennison, Steven Waguespack, Kim-Ahn Do, Sunita Agarwal, Mary Walter, James Welch, Lee Weinstein, Jenny E. Blau, Smita Jha, Naris Nilubol, Menno R. Vriens, Rachel S. van Leeuwaarde, Mark J. van Treijen, Gerlof D. Valk, Nancy D. Perrier, Samir M. Hanash, Johannes F. Fahrmann. A blood-based microbial metabolites signature for associated with metastatic duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2002.

BACKGROUND:Recent data suggest that cytoreductive surgery in metastatic adrenocortical carcinoma) may improve survival. However, successful removal of locally invasive primary tumors in such patients may require complex en bloc and/or multivisceral resection, for which the survival benefits remain unclear. METHODS:We retrospectively analyzed 153 patients with metastatic adrenocortical carcinoma treated at our institution from 1998 to 2024. Patients were categorized into 3 groups based on treatment approach: multivisceral resection, adrenalectomy alone, and nonoperative management. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival across these groups. RESULTS:Among 153 patients (52% female; median age 49 years, interquartile range: 36-59 years), 24% underwent multivisceral resection, 18% had adrenalectomy alone, and 58% were managed nonoperatively. Overall, 68% of tumors were functional. The most frequent metastatic sites were the lung (71%) and liver (66%). The most frequent en bloc procedures included radical nephrectomy (64%) and partial hepatectomy (47%). The median overall survival was 33 months after multivisceral resection, 22 months after adrenalectomy alone, and 7 months with nonoperative management (P < .0001). On multivariable analysis, multivisceral resection (hazards ratio = 0.31, 95% confidence interval: 0.18-0.50, P < .0001) and adrenalectomy alone (hazards ratio = 0.50, 95% confidence interval: 0.28-0.88, P = .017) were independently associated with longer overall survival compared with nonoperative management. CONCLUSION:Cytoreductive surgery, including multivisceral resection, may be associated with improved survival in metastatic adrenocortical carcinoma compared with nonoperative management. However, given the potential risks of these complex operations, they should be judiciously performed in select patients by experienced multidisciplinary teams.

Metastatic duodenopancreatic neuroendocrine tumors (dpNETs) are the primary cause of mortality among patients with Multiple Endocrine Neoplasia Type 1 (MEN1). Emerging evidence implicates the microbiome and microbial-derived secreted factors in promoting cancer development and progression. In the current study, we report that the circulating microbial-associated uremic toxins trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), cresol sulfate (CS), cresol glucuronide (CG), and phenol sulfate (PS) are elevated in MEN1 patients with metastatic dpNETs. Proteomic- and metabolomic-based analysis of resected dpNET tissues from MEN1 patients also revealed detectable levels of uremic toxins that positively correlated with peptide-based signatures corresponding to Fusobacterium nucleatum, Faecalibacterium prausnitzii, and Klebsiella pneumoniae and negatively correlated with Streptococcus pneumoniae and Streptococcus thermophilus. A microbial-associated uremic toxin panel (MUTP) was developed and, in an independent case-control validation cohort, the panel yielded an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.85-1.00) with 67% sensitivity at 95% specificity for identifying MEN1 patients with metastatic dpNETS. Increases in circulating microbial-associated uremic toxins during early stages of neoplasia were also found to be associated with poor overall survival in an Men1fl/flPdx1-CreTg mouse model of MEN1 pancreatic NETs. Our findings suggest that microbial dysbiosis is associated with disease aggressiveness and that increases in circulating microbial-associated uremic toxins may be a prognostic indication for MEN1 individuals who are at risk of having metastatic dpNETs.