The lesion detection rate of Ga-68 DOTATATE PET/MR in multiple endocrine neoplasia type 1.

INTRODUCTION: The purpose of the study was to determine the usefulness of Ga-68 DOTATATE PET/MR in the identification of tumours in individuals with multiple endocrine neoplasia type 1 (MEN1). METHODS: In this retrospective investigation, five individuals who had tested positive for a hereditary MEN1 variant underwent Ga-68 DOTATATE PET/MR between May 2020 and January 2023. Several types of tumours associated with MEN1 were studied. MEN1-related tumours included pituitary, parathyroid, gastroenteropancreatic, and adrenal. The rates of lesion identification between MRI, Ga-68 DOTATATE PET, and Ga-68 DOTATATE PET/MRI were examined. The maximum and mean standard uptake values (SUVmax and SUVmean) were evaluated in carefully delineated volumes of interest (VOI) for the relevant tumours. RESULTS: Of the 24 primary lesions, 14 were identified by Ga-68 DOTATATE PET, 18 by MRI, and 20 by Ga-68 DOTATATE PET/MRI. Two pituitary tumours were detected by all three techniques. All parathyroid tumours that were not detected by Ga-68 DOTATATE PET and MRI were found by Tc-99m MIBI SPECT/CT or/and EUS. Ga-68 DOTATATE PET/MR detected more gastroenteropancreatic lesions. All adrenal tumours not identified by Ga-68 DOTATATE PET were found by MRI or CT. The median SUVmax for lesions identified on Ga-68 DOTATATE PET/MRI was 18.4 (range, 3.8-85.2), and the median SUVmean was 12.0 (range, 2.3-49.8). CONCLUSION: The combination of Ga-68 DOTATATE PET and MRI demonstrated a higher detection rate and may be more useful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. To increase the identification of MEN1-associated neuroendocrine lesions in the parathyroid gland, approaches other than Ga-68 DOTATATE PET/MRI should be used.

Imaging surveillance in multiple endocrine neoplasia type 1: Ten years of experience with somatostatin receptor positron emission tomography.

Guidelines for multiple endocrine neoplasia type 1 (MEN1) recommend intensive imaging surveillance without specifying a superior regimen, including the role of somatostatin receptor imaging (SRI) with positron emission tomography (PET). The primary outcomes were to: (1) Assess change in treatment of duodenal-pancreatic neuroendocrine neoplasms (DP-NENs), bronchopulmonary NENs, and thymic tumors attributed to use of SRI PET/computed tomography (CT) and (2) estimate radiation from imaging and risk of cancer death attributed to imaging radiation. This was a retrospective single center study, including all MEN1 patients, who had had at least one SRI PET/CT. A total of 60 patients, median age 42 (range 21-54) years, median follow-up 6 (range 1-10) years were included. Of 470 cross sectional scans (MRI, CT, SRI PET/CT), 209 were SRI PET/CT. The additional information from SRI PET had implications in 1/14 surgical interventions and 2/12 medical interventions. The estimated median radiation dose per patient was 104 (range 51-468) mSv of which PET contributed with 13 (range 5-55) mSv and CT with 91 mSv (range 46-413 mSv), corresponding to an estimated increased median risk of cancer death of 0.5% during 6 years follow-up. SRI PET had a significant impact on 3/26 decisions to intervene in 60 MEN1 patients followed for a median of 6 years with SRI PET/CT as the most frequently used modality. The surveillance program showed a high radiation dose. Multi-modality imaging strategies designed to minimize radiation exposure should be considered. Based on our findings, SRI-PET combined with CT cannot be recommended for routine surveillance in MEN1 patients.

[Thymic Neuroendocrine Tumor Associated with Multiple Endocrine Neoplasia Type 1].

Multiple endocrine neoplasia (MEN) type 1 is a hereditary syndrome characterized by hyperplasia and adenoma of the parathyroid gland, pancreatic tumor, and pituitary tumor. We report a rare case of thymic neuroendocrine tumor diagnosed after removal of a thymic tumor following pancreatic and parathyroid surgery. A 35-year-old man was diagnosed with MEN type 1 by hypercalcemia and gastrinemia with a ureteral tone. Two well defined nodules in the anterior mediastinum on computed tomography (CT), and a high degree of accumulation on positron emission tomography (PET) was noted. Surgery was performed through a median sternotomy with anterior mediastinal tumor resection. Pathology showed thymic neuroendocrine tumor (NET). Immunostaining results were different from pancreatic NET and duodenal NET, and a diagnosis of primary thymic NET was made. Postoperative radiation therapy was completed as adjuvant therapy, and the patient is alive without reccurrence.

Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice.

Background: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the diagnostic accuracy of the currently used conventional pancreatic imaging techniques and the added value of fine needle aspirations (FNAs). Methods: Patients who had at least one imaging study were included from the population-based MEN1 database of the DutchMEN Study Group from 1990 to 2017. Magnetic resonance imaging (MRI), computed tomography (CT), endoscopic ultrasonography (EUS), FNA, and surgical resection specimens were obtained. The first MRI, CT, or EUS was considered as the index test. For a comparison of the diagnostic accuracy of MRI versus CT, patients with their index test taken between 2010 and 2017 were included. The reference standard consisted of surgical histopathology or radiological follow-up. Results: A total of 413 patients (92.8% of the database) underwent 3,477 imaging studies. The number of imaging studies per patient increased, and a preference for MRI was observed in the last decade. Overall diagnostic accuracy was good with a positive (PPV) and negative predictive value (NPV) of 88.9% (95% confidence interval, 76.0-95.6) and 92.8% (89.4-95.1), respectively, for PanNET in the pancreatic head and 92.0% (85.3-96.0) and 85.3% (80.5-89.1), respectively, in the body/tail. For MRI, PPV and NPV for pancreatic head tumors were 100% (76.1-100) and 87.1% (76.3-93.6) and for CT, 60.0% (22.9-88.4) and 70.4% (51.3-84.3), respectively. For body/tail tumors, PPV and NPV were 91.3% (72.0-98.8) and 87.0% (75.3-93.9), respectively, for MRI and 100% (74.9-100) and 77.8% (54.3-91.5), respectively, for CT. Pathology confirmed a PanNET in 106 out of 110 (96.4%) resection specimens. FNA was performed on 34 lesions in 33 patients and was considered PanNET in 24 [all confirmed PanNET by histology (10) or follow-up (14)], normal/cyst/unrepresentative in 6 (all confirmed PanNET by follow-up), and adenocarcinoma in 4 (2 confirmed and 2 PanNET). Three patients, all older than 60 years, had a final diagnosis of pancreatic adenocarcinoma. Conclusion: As the accuracy for diagnosing MEN1-related PanNET of MRI was higher than that of CT, MRI should be the preferred (non-invasive) imaging modality for PanNET screening/surveillance. The high diagnostic accuracy of pancreatic imaging and the sporadic occurrence of pancreatic adenocarcinoma question the need for routine (EUS-guided) FNA.

68Ga-DOTATATE PET/CT imaging for insulinoma in MEN1 patient with endogenous hyperinsulinemic hypoglycemia: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare and complicated disease that is associated with several endocrine tumors. Here, we report a case of MEN1 associated with insulinoma, parathyroid, and pituitary tumors by 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT). PATIENT CONCERNS: A 49-year-old woman presented with intermittent hypoglycemia for more than a year and developed indistinct consciousness without an apparent trigger. DIAGNOSES: Biochemical results showed abnormally high serum insulin and parathyroid hormone levels. She underwent an Abdominal magnetic resonance imaging revealed a small nodule in the uncinate process of the pancreas, but it did not clarify the nature of the small nodule. Pituitary magnetic resonance imaging scan revealed a micropituitary tumor, and parathyroid imaging showed no abnormalities. 18F-FDG PET/CT showed no apparent abnormal 18F-FDG uptake in the whole body. In contrast, 68Ga-DOTATATE PET/CT imaging showed pathological radiotracer uptake in the pancreatic uncinate process, accompanied by mild radiotracer uptake in the pituitary gland, and no apparent abnormal radiotracer uptake in the parathyroid area. INTERVENTIONS: The patient underwent echoendoscopy for pancreatic uncinate process lesions and surgical resection. OUTCOMES: Histological analysis was suggested of insulinoma of pancreatic neuroendocrine tumor, the Ki-67 index was low (only 1% being positive). LESSONS: This case demonstrates that 68Ga-DOTATATE can be used for the detection of MEN1-related tumors and preoperative localization of small and low-grade insulinomas by PET/CT.

The role of 18F-FDG PET/CT and single isotope 99mTc-tetrofosmin scintigraphy combined with SPECT in diagnosis of multiple endocrine neoplasia type 1 syndrome.

We present a case of a 47-year-old woman with type 1 multiple endocrine neoplasia, primary hyperparathyroidism, insulinoma, and nonfunctioning pituitary adenoma. In July 2017, the patient was referred to the Department of Nuclear Medicine of St George University Hospital in Plovdiv for a PET/CT scan because of persistent hypoglycemic episodes and high serum insulin levels. A whole-body PET/CT examination was performed 65 min after intravenous application of 188 MBq 18F-FDG on a hybrid PET/CT scanner (Biograph mCT 64, Siemens). We detected a low metabolically active lesion 10 mm in diameter (SUVmax - 2.00), located below the left thyroid lobe suspicious for parathyroid adenoma. In the remaining scanned areas there were no PET/CT data for other areas with increased glucose metabolism with malignant characteristics that could be associated with the underlying disease.

Intraoperative Ultrasound Guided Laparoscopic Spleen-Preserving Distal Pancreatectomy for Primitive Neuroendocrine Tumors in a Pediatric Patient With MEN-1.

This case details the presentation and surgical management of a 15-year-old male patient with multiple endocrine neoplasia syndrome type 1 (MEN1) who required distal pancreatectomy for multiple nonfunctional pancreatic tumors. An intraoperative ultrasound was utilized to allow for proper location of the distal pancreatectomy, as well as visualization of the splenic vessel relationships and to ensure all lesions were contained within the specimen. Pathology demonstrated 5 well-differentiated neuroendocrine tumors with no evidence of malignancy. This case utilized innovative technology and a multidisciplinary approach in a challenging case to achieve a safe minimally invasive resection. The use of ultrasound intraoperatively provided confidence that all lesions had been identified, as well as demonstration of safe planes separate from the nearby vasculature.

68Ga-DOTANOC PET/CT in Multiple Endocrine Neoplasia 1 With Associated Adrenocortical Carcinoma.

ABSTRACT: Multiple endocrine neoplasia 1 (MEN1) syndrome is an autosomal dominant syndrome comprising a triad of pancreatic, pituitary, and parathyroid tumors. Adrenal cortical carcinoma occurs rarely in MEN1 syndrome. Here, we have presented a case of a 62-year-old woman with adrenal mass and elevated serum parathormone levels, who underwent 68Ga-DOTANOC PET/CT. 68Ga-DOTANOC PET/CT showed intense tracer concentration in the left adrenal mass and lesions in the liver, pancreas, and peritoneum. Biopsy of the peritoneal deposit revealed metastatic adrenocortical carcinoma, and further genetic testing showed MEN1 mutation.

Multiple endocrine neoplasia type 1 or 4: detection of hyperfunctioning parathyroid glands with 18F-fluorocholine PET/CT. Illustrative cases and pitfalls.

18F-fluorocholine (FCH) PET/CT is now well established to detect the hyperfunctioning parathyroid glands (HFPTG) in a case of sporadic primary hyperparathyroidism (pHPT), but only limited evidence is available about the utility of FCH PET/CT to detect the HFPTG in patients with multiple endocrine neoplasia (MEN) type 1 or 4. The pHPT in this context frequently consists in a multiglandular disease with small hyperplastic glands rather than adenomas, which is challenging for imaging modalities. The data of patients with MEN1 or MEN4 after parathyroidectomy referred to FCH PET/CT for presurgical localization of HFPTG were retrospectively reviewed, including follow-up after parathyroidectomy, in search for diagnostic performance and for potential pitfalls. In the present cohort, 16 patients referred to FCH PET/CT as part of their initial pHPT work-up were subsequently operated, 44 abnormal parathyroid glands (PT) were resected, of which 32 (73%) had been detected on FCH PET/CT and 2 considered as equivocal foci. Nine patients referred to FCH PET/CT for recurrent pHPT who were subsequently operated, 14 abnormal PT were resected, all had been detected on FCH PET/CT. FCH PET/CT permitted a unilateral approach for PTx in 4 of them. In one patient with MEN4 and pHPT, the HFPTG could not be visualized on FCH PET/CT but was localized by ultrasonography. Several causes of false positive or false negative results, incidental finding and pitfalls are listed and discussed. FCH PET/CT has a positive benefit/risk ratio in the detection of HFPTG in case of MEN1 (the data in MEN4 being currently very limited) with the most effective detection rate of current imaging modalities for HFPTG, few pitfalls, and an adequate impact on patient management compared to sesta MIBI SPECT and ultrasonography.

Regional Growth Velocity and Incidence of Pancreatic Neuroendocrine Neoplasias in Multiple Endocrine Neoplasia Type 1.

OBJECTIVES: Pancreatic neuroendocrine neoplasias (pNENs) in multiple endocrine neoplasia type 1 are predominantly found in the dorsal anlage. Whether their growth velocity and incidence might be related to their location in the pancreas has not been investigated yet. METHODS: We studied 117 patients using endoscopic ultrasound. RESULTS: Growth velocity could be calculated for 389 pNENs. Increase of largest tumor diameter (% per month) was 0.67 (standard deviation [SD], 2.04) in the pancreatic tail (n = 138), 1.12 (SD, 3.00) in the pancreatic body (n = 100), 0.58 (SD, 1.19) in the pancreatic head/uncinate process-dorsal anlage (n = 130), and 0.68 (SD, 0.77) in the pancreatic head/uncinate process-ventral anlage (n = 12). Comparing growth velocity of all pNENs in the dorsal (n = 368, 0.76 [SD, 2.13]) versus ventral anlage, no significant difference was detected. Annual tumor incidence rate was 0.21 in the pancreatic tail, 0.13 in the pancreatic body, 0.17 in the pancreatic head/uncinate process-dorsal anlage, 0.51 dorsal anlage together, and 0.02 in the pancreatic head/uncinate process-ventral anlage. CONCLUSIONS: Multiple endocrine neoplasia type 1 pNENs are unequally distributed between ventral (low prevalence and incidence) and dorsal anlage. However, there are no regional differences in growth behavior.

Value of Somatostatin Receptor PET/CT in Patients With MEN1 at Various Stages of Their Disease.

CONTEXT: Despite the growing evidence of the clinical value of somatostatin receptor (SSTR) positron emission tomography (PET) in the evaluation of neuroendocrine tumors (NETs), its role remains to be clarified at different time points in the journey of patients with multiple endocrine neoplasia type 1 (MEN1). The rarity of the disease is however a significant impediment to prospective clinical trials. OBJECTIVE: The goals of the study were to assess the indications and value of SSTR PET/computed tomography (CT) in patients with MEN1. METHODS: We retrospectively included patients from 7 French expert centers for whom data on SSTR PET/CT and morphological imaging performed at the same period were available. Detection rates of PET study were analyzed. RESULTS: One hundred and 8 patients were included. SSTR PET/CT was performed at screening (n = 33), staging (n = 34), restaging (n = 37), and for peptide receptor targeted radiotherapy selection (n = 4). PET detected positive pancreatic lesions in 91% of cases at screening, with results comparable with magnetic resonance imaging but superior to CT (P = .049). Metastases (mostly lymph node [LN]) were present at the screening phase in 28% of cases, possibly due to the suboptimal value of screening morphological imaging in the assessment of nodal metastases and/or a long delay between imaging studies. SSTR PET/CT was considered superior or complementary to the reference standard in the assessment of LN or distant metastases in the vast majority of cases and regardless of the clinical scenario. CONCLUSION: This study shows the potential added value of SSTR PET in the assessment of MEN1-associated NETs and provides great impetus toward its implementation in the evaluation of patients with MEN1.

A rare case of multiple endocrine neoplasia type 1 initially presenting as an asymptomatic, huge mediastinal mass: case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited syndrome that concurrently involves various endocrine glands. We report a rare case of MEN1 in a 43-year-old man whose first manifestation was an asymptomatic mediastinal mass. CASE PRESENTATION: A 13-cm-sized mediastinal mass was diagnosed as an atypical thymic carcinoid by computed tomography and percutaneous needle biopsy. In addition, hypercalcemia from a left inferior parathyroid hyperplasia, and a non-functioning gastric neuroendocrine tumor seen on esophagogastroduodenoscopy were found. Therefore, the patient was clinically diagnosed with MEN1 syndrome, and underwent surgical resection of thymic carcinoid tumor after pre-operative concurrent chemoradiation therapy to decrease tumor size and volume. Parathyroid lesion and gastric neuroendocrine tumor were also removed. Finally, a MEN1 gene mutation was observed in the patient and his 7-year-old son. CONCLUSION: Despite its rare occurrence, thymic carcinoid tumor should be considered as a MEN1-associated tumor and necessitates screening of other endocrine glands. Thymic carcinoid tumor carries a poor prognosis in patients with MEN1, and thus it needs to be carefully monitored even after radical excision.

Multiple endocrine neoplasia type 1 with refractory hypoglycemia and lung and liver metastases: a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant genetic disease. MEN1 with multiple endocrine adenomatosis complicated by multiple endocrine tumors is often misdiagnosed or missed. Herein, we describe the first reported case of refractory hypoglycemia and liver and lung metastases in a patient with MEN1.Case presentation: A 40-year-old man presented with a 3-month history of intermittent palpitations, fatigue, and sweating. The patient had a history of prolactinoma resection and refractory hypoglycemia 2 years earlier. Analyses of blood samples showed a decrease in random and fasting blood glucose and an increase in prolactin (PRL). Computed tomography (CT) and magnetic resonance imaging scans revealed two substantial masses in the pancreas and large masses in the liver and lung. Positron emission tomography-CT images showed hypermetabolic masses in the pancreatic body and tail. The liver and lung lesions were also hypermetabolic. The pancreatic lesion was surgically removed, and pathology confirmed that the mass was MEN1. The liver and lung masses were confirmed as metastatic tumors. CONCLUSION: If clinicians better understand MEN1, they can obtain a detailed patient and family history during the initial visit, allowing earlier diagnosis and intervention and improved prognosis.

Pancreatic Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: Diagnostic Value of Different MRI Sequences.

BACKGROUND: MRI is a useful imaging modality to assess the presence of pancreatic neuroendocrine tumors (PNETs), allowing repeat monitoring examinations in multiple endocrine neoplasia type 1 (MEN-1) patients. OBJECTIVES: We aimed to compare the diagnostic accuracy of conventional MRI sequences to identify which sequence better depicts the presence of PNETs in MEN-1 patients. METHOD: We performed a retrospective analysis of consecutive MEN-1 patients who underwent a conventional MRI protocol to monitor previously proven PNETs. MRI sequences T1-w chemical shift (CS), T2-w HASTE, fat-suppressed (FS) T2-w HASTE, diffusion-weighted imaging (DWI), and pre- and post-contrast FS T1-w sequences were independently analyzed by 2 experienced radiologists using a 3-grade score (no lesion, uncertain lesion, and certain lesion); lesion size and signal intensity were recorded. A Friedman ANOVA and a Wilcoxon pairwise test for the post hoc analysis were used. The sensitivity of each sequence was measured, and the results were analyzed with the χ2 test. RESULTS: We included 21 patients with a total of 45 PNETs proven by histology, endoscopic ultrasonography-guided fine-needle aspiration, CT, and nuclear medicine studies. A statistically significant (p < 0.01) difference was observed in the detection performance of each MRI sequence, particularly between DWI (91%) and T2-w FS (85%) sequences in comparison to the others (T1-w CS, T2-w, and pre- and post-contrast FS T1-w, ≤56% for all); no significant (p = 0.5) difference was found between the detection performance of DWI and T2-w FS sequences. No correlation was observed between the qualitative score of each sequence and lesion tumor size. CONCLUSIONS: DWI and T2-w FS sequences proved to be the most accurate in the detection of PNETs, thus suggesting a role for an abbreviated MRI protocol without contrast medium administration for monitoring MEN-1 patients.

Reliability and Agreement of Radiological and Pathological Tumor Size in Patients with Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors: Results from a Population-Based Cohort.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still regarded as the main prognostic factor and therefore used for surgical decision-making. We assessed reliability and agreement of radiological and pathological tumor size in a population-based cohort of patients with MEN1-related pNETs. METHODS: Patients were selected from the Dutch MEN1 database if they had undergone a resection for a pNET between 2003 and 2018. Radiological (MRI, CT, and endoscopic ultrasonography [EUS]) and pathological tumor size were collected from patient records. Measures of agreement (Bland-Altman plots with limits of agreement [LoA] and absolute agreement) and reliability (intraclass correlation coefficients [ICC] and unweighted kappa) were calculated for continuous and categorized (< or ≥2 cm) pNET size. RESULTS: In 73 included patients, the median radiological and pathological tumor sizes measured were 22 (3-160) and 21 (4-200) mm, respectively. Mean bias between radiological and pathological tumor size was -0.2 mm and LoA ranged from -12.9 to 12.6 mm. For the subgroups of MRI, CT, and EUS, LoA of radiological and pathological tumor size ranged from -9.6 to 10.9, -15.9 to 15.8, and -13.9 to 11.0, respectively. ICCs for the overall cohort, MRI, CT, and EUS were 0.80, 0.86, 0.75, and 0.76, respectively. Based on the 2 cm criterion, agreement was 81.5%; hence, 12 patients (18.5%) were classified differently between imaging and pathology. Absolute agreement and kappa values of MRI, CT, and EUS were 88.6, 85.7, and 75.0%, and 0.77, 0.71, and 0.50, respectively. CONCLUSION: Within a population-based cohort, MEN1-related pNET size was not systematically over- or underestimated on preoperative imaging. Based on agreement and reliability measures, MRI is the preferred imaging modality.

3P's of Wermer/MEN1 Syndrome on 68Ga-DOTANOC PET/CT Scan.

Wermer/MEN1 syndrome is composed of the triad of pancreatic, pituitary, and parathyroid (3P's) tumors. We describe the Ga-DOTANOC PET/CT findings of a 43-year-old man, which revealed the classic 3P's of MEN1 syndrome with somatostatin receptor expression. The patient further underwent surgery for parathyroid lesions, which were suggestive of adenomas.