Severe ectopic Cushing syndrome in a transgender man with a metastatic gastrinoma and an adrenal tumor-A case report and review of the literature.

A 38-year-old transgender man with advanced metastatic functional pancreatic neuroendocrine neoplasm (PanNEN) gastrinoma was admitted to the Department of Endocrinology due to severe ACTH-dependent hypercortisolemia. An ectopic production of ACTH by PanNEN was suspected. The patient qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent resection of the left adrenal gland with the tumor only, which surprisingly resulted in a significant decrease in ACTH and cortisol levels, leading to clinical improvement. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. We looked for a correlation between gender-affirming hormone treatment and the onset of the disease and its rapid progression. This may be the first case describing the coexistence of gastrinoma and ectopic Cushing disease in a transsexual patient.

All you need to know about gastrinoma today | Gastrinoma and Zollinger-Ellison syndrome: A thorough update.

Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 µg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.

Recurrence after surgical resection of nonmetastatic sporadic gastrinoma: Which prognostic factors and surgical procedure?

BACKGROUND: The only curative treatment of gastrinoma is complete resection, but its surgical management remains controversial and prognostic factors of sporadic nonmetastatic gastrinoma are poorly known. METHODS: This was a retrospective study including all patients who underwent elective surgery for nonmetastatic sporadic gastrinoma between 2000 and 2020 in 15 hospitals. The primary and secondary outcomes were overall survival and disease-free survival predictive factors. RESULTS: In total, 108 patients were included, of which 68 (63%) were duodenal, 19 (18%) pancreatic, and 21 (19%) primary lymph node gastrinomas, with no major difference in clinical presentation. Among the 68 duodenal gastrinomas, 26% (n = 18) underwent pancreaticoduodenectomy (PD) and 74% (n = 50) underwent duodenotomy with the excision of duodenal wall tumors and lymphadenectomy (DUODX + LN). Overall, the median overall survival was 173 months, and the 5-year overall survival was 94%, with no predictive factors identified. The median disease-free survival was 93 months, and the 5-year disease-free survival was 63%. Tumor size >2 cm (P = .00001), grade (P = .00001), and pancreatic tumor location (P = .0001) were predictive factors of recurrence; however, in multivariate analysis, only tumor size >2 cm (P = .005) and grade (P = .013) were independent predictors of recurrence. Age, sex, preoperative gastrin level, lymphadenectomy <10 resected lymph nodes, and metastatic lymph nodes on surgical specimens were not predictors of recurrence. For duodenal gastrinomas, surgical procedures (PD versus DUODX + LN) did not have a significant effect on overall survival and disease-free survival. CONCLUSION: Sporadic nonmetastatic gastrinomas had an excellent overall survival. Recurrence is frequent and influenced by tumor size and grade. Regarding sporadic duodenal gastrinoma, duodenotomy with excision of duodenal wall tumors with lymphadenectomy could be considered a valid surgical option, in the absence of clear oncologic superiority of PD.

Quantitative characterization of duodenal gastrinoma autofluorescence using multiphoton microscopy.

BACKGROUND: Duodenal gastrinomas (DGASTs) are neuroendocrine tumors that develop in the submucosa of the duodenum and produce the hormone gastrin. Surgical resection of DGASTs is complicated by the small size of these tumors and the tendency for them to develop diffusely in the duodenum. Endoscopic mucosal resection of DGASTs is an increasingly popular method for treating this disease due to its low complication rate but suffers from poor rates of pathologically negative margins. Multiphoton microscopy can capture high-resolution images of biological tissue with contrast generated from endogenous fluorescence (autofluorescence [AF]) through two-photon excited fluorescence (2PEF). Second harmonic generation is another popular method of generating image contrast with multiphoton microscopy (MPM) and is a light-scattering phenomenon that occurs predominantly from structures such as collagen in biological samples. Some molecules that contribute to AF change in abundance from processes related to the cancer disease process (e.g., metabolic changes, oxidative stress, and angiogenesis). STUDY DESIGN/MATERIALS AND METHODS: MPM was used to image 12 separate patient samples of formalin-fixed and paraffin-embedded duodenal gastrinoma slides with a second-harmonic generation (SHG) channel and four 2PEF channels. The excitation and emission profiles of each 2PEF channel were tuned to capture signal dominated by distinct fluorophores with well-characterized fluorescent spectra and known connections to the physiologic changes that arise in cancerous tissue. RESULTS: We found that there was a significant difference in the relative abundance of signal generated in the 2PEF channels for regions of DGASTs in comparison to the neighboring tissues of the duodenum. Data generated from texture feature extraction of the MPM images were used in linear discriminant analysis models to create classifiers for tumor versus all other tissue types before and after principal component analysis (PCA). PCA improved the classifier accuracy and reduced the number of features required to achieve maximum accuracy. The linear discriminant classifier after PCA distinguished between tumor and other tissue types with an accuracy of 90.6%-93.8%. CONCLUSIONS: These results suggest that multiphoton microscopy 2PEF and SHG imaging is a promising label-free method for discriminating between DGASTs and normal duodenal tissue which has implications for future applications of in vivo assessment of resection margins with endoscopic MPM.

How to treat gastrinomas in patients with multiple endocrine neoplasia type1: surgery or long-term proton pump inhibitors?

In patients with multiple endocrine neoplasia type 1 syndrome (MEN 1) and Zollinger-Ellison syndrome (ZES), gastrinomas arise from the duodenum, about 60% are multiple, and about 15% of patients have coexisting pancreatic gastrinomas, which can be localized by the selective arterial secretagogue injection test (SASI test). The guidelines (GLs) by the Japanese Neuroendocrine Tumor Society (JNETS) recommend surgical resection for functioning duodenopancreatic neuroendocrine tumors (NETs), including gastrinomas, in patients with MEN1 (Grade A, 100% agreement among members). Conversely, the GLs of the National Comprehensive Cancer Network (NCCN) in the USA recommend observation and treatment with proton pump inhibitors (PPIs) or exploratory surgery for occult gastrinomas. An international Consensus Statement (ICS) from the European Union (EU) also does not recommend resection of gastrinomas in patients with MEN1, despite some surgeons having reported surgery being curative for gastrinomas in MEN1 patients. In this review, we discuss the serious side effects and tumorigenic effects of the prolonged use of PPIs and the safety and curability of surgery, supported by our results of curative surgery for gastrinomas in 20 patients with MEN1 over 30 years. We conclude that surgery should be the first-line treatment for gastrinomas in MEN1 patients.

Duodenal gastrinoma - case report.

INTRODUCTION: In our text, we want to highlight a rare diagnosis. CASE REPORT: A 54-year-old obese, hypertensive male smoker had been investigated for intermittent abdominal pain for 12 years. The first gastroscopy for a bleeding ulcer was conducted in 2010. In the subsequent years, repeated gastroscopies revealed variable involvement from the esophagus to the duodenum. Capsule enteroscopy did not provide further specification of the diagnosis. The patient underwent colonoscopy and MRI enterography multiple times, with no unequivocal pathological findings. In May 2022, he was admitted to our department for abdominal pain and vomiting. This time, gastroscopy revealed multiple small ulcers in the duodenum and jejunum with clots causing a mechanical obstruction. Chromogranin A was elevated, raising suspicion of gastrinoma. However, somatostatin receptor-based imaging (Octreoscan) was negative. Only the 68Ga-DOTATOC PET (positron emission tomography with the radiopharmaceutical DOTA, labeled with gallium-68) identified a lesion in the subhepatic region, which had no correlation on CT. We concluded the diagnosis as gastrinoma with the Zollinger-Ellison syndrome. Endoscopically, a 1cm tumor was found in the duodenum. In October 2022, the patient underwent an excision of the duodenal wall, and the pathology assessment confirmed our diagnosis of gastrinoma. CONCLUSION: With this case report, we want to emphasize the importance of taking into account neuroendocrine tumors in our differential diagnostic considerations. At the same time, we want to highlight that, according to ESMO recommendations, we should preferentially use 68Ga-DOTATOC PET/CT for the diagnosis instead of scintigraphic examination (111In-Octreoscan).

[Primary lymph node gastrinoma]. / Gastrinoma primario de ganglio linfático.

Gastrinomas are neuroendocrine tumors usually located in the duodenum and pancreas, in the context of a Multiple Endocrine Neoplasm and forming a Zollinger-Ellison syndrome. The location of this type of lymph node tumor is extremely unusual and its early diagnosis constitutes a real challenge to be able to establish an adequate treatment and manage the complications that these entail. We present the case of a 64-year-old male patient with a lymph node gastrinoma and whose surgical removal resulted in the immediate remission of the patient's symptoms.

A case of refractory esophageal stricture due to occult gastrinoma of the duodenum.

Gastrinoma may cause refractory esophageal stricture due to gastro-esophageal reflux disease (GERD), but imaging technologies have limited power in its diagnosis. A 74-year-old female with a history of peptic ulcers suffered from repeated epigastralgia, and she visited a local hospital. An esophago-gastro-duodenoscopy (EGD) demonstrated severe reflux esophagitis and multiple peptic ulcers. Blood examination revealed a high value of fasting serum gastrin. Multi-detector computed tomography showed a hypervascular and tiny nodule in duodenal bulb, although other imaging technologies did not. Short-term medication with a proton pump inhibitor or potassium-competitive acid blocker was intermittently provided, but dysphagia was repeatedly worsened, and she was referred to our division. Serum hypergastrinemia was retained, and EGD reexamination depicted esophageal stricture, treated by multiple sessions of endoscopic balloon dilatation. Primary tumor was not identified by the morphological imaging technologies, but a selective arterial secretagogue injection test suggested its existence in the duodenum or pancreatic head. Pancreaticoduodenectomy was performed, and histological study identified 2 mm-sized microgastrinoma buried in Brunner`s glands on the posterior wall of the duodenum bulb. We reported a case with difficulty in diagnosis of the smallest sporadic gastrinoma of the duodenum, which might cause refractory GERD-associated stricture.

Sequential therapies in gastric gastrinoma.

Not required for Clinical Vignette.

Primary hepatic gastrinoma, extremely rare case presentation and its surgical resolution, in a third level hospital in Mexico.

The gastrinomas are rare functional neuroendocrine neoplasms, most are localized to the duodenum (70-90%) or the pancreas (2-30%), but less common ectopic sites have been reported. The primary hepatic gastrinoma is extremely rare, with less tan 40 cases reported in the medical literature. Its low incidence and its non specific clinical presentation make it a difficult disease to diagnose. Providing a timely diagnosis the patient can be treated by surgical resection with high chances of success. The objective of this paper is to describe a case of primary hepatic gastrinoma in Mexico, successfully treated by right liver segmentectomy.

Los gastrinomas son neoplasias neuroendocrinas funcionales raras, y la mayoría se localizan en el duodeno (70-90%) o en el páncreas (2-30%), pero también existen otras localizaciones ectópicas poco comunes. El gastrinoma hepático primario es extremadamente raro, con menos de 40 casos reportados en la literatura médica. Su baja incidencia y su presentación clínica inespecífica lo convierten en una enfermedad difícil de diagnosticar. Al realizar un diagnóstico oportuno puede ser tratado mediante resección quirúrgica con altas posibilidades de éxito. El objetivo de este trabajo es presentar un caso clínico de gastrinoma hepático primario en México, tratado de manera exitosa mediante segmentectomía hepática derecha.

Combined surgical and medical management of a cat with gastrinoma.

Gastrinomas are gastrin-secreting pancreatic tumours rarely diagnosed in cats. A 12-year-old female spayed cat was presented for vomiting, anorexia and weight loss. Physical exam revealed lethargy, dehydration and thin body condition. Pertinent laboratory abnormalities included a mild mature neutrophilia and borderline hypoalbuminaemia. Imaging of the abdomen revealed a mass-like change to the proximal duodenum. Exploratory laparotomy was performed, and the duodenal mass along with a 3-mm pancreatic nodule was removed. Immunohistochemical staining of the pancreatic nodule confirmed a gastrinoma. Following surgery, treatment was initiated with omeprazole and toceranib. Toceranib was discontinued after 8 weeks due to hyporexia. The patient was continued on omeprazole long term and has survived more than 35 months since diagnosis. Little information regarding treatment and prognosis for feline gastrinomas is available. In this case report, long-term survival was achieved with a combined surgical and medical approach using omeprazole and toceranib.

Hormonal tumor mapping for liver metastases of gastroenteropancreatic neuroendocrine neoplasms: a novel therapeutic strategy.

PURPOSE: In patients with metastatic functional gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), it is unknown what degree of tumor reduction is required to eliminate hormonal symptoms. We aimed to reduce hormonal symptoms derived from advanced GEP-NENs by efficient minimal intervention, constructing a hormonal tumor map of liver metastases. METHODS: Between 2013 and 2019, we treated 12 insulinoma or gastrinoma patients with liver metastases. Liver segments containing hormone-producing tumors were identified by injecting calcium gluconate via the hepatic arteries and monitoring the change in serum hormone concentration in the three hepatic veins. A greater-than-twofold increase in hormone concentration indicated a tumor-feeding vessel. RESULTS: Cases included eight insulinomas and four gastrinomas. Primary lesions were functional in three patients and nonfunctional in 9. Nine patients showed hormonal step-up indicating the presence of functional lesions; eight showed step-up in tumor-bearing liver segments, while one with synchronous liver metastases showed step-up only in the pancreatic region. Five patients underwent surgery. Serum hormone concentration decreased markedly after removing the culprit lesions in 3; immediate improvement in hormonal symptoms was achieved in all patients. Three patients with previous surgical treatment who showed step-up underwent transcatheter arterial embolization, achieving temporary improvement of hormonal symptoms. Four patients showed unclear localization of the hormone-producing tumors; treatment options were limited, resulting in poor outcomes. CONCLUSION: Hormonal tumor mapping demonstrated heterogeneity in hormone production among primary and metastatic tumors of GEP-NENs. Minimally invasive treatment based on hormonal mapping may be a viable alternative to conventional cytoreduction.

A germline c.1546dupC MEN1 mutation in an MEN1 family: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors. PATIENT CONCERNS: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma. DIAGNOSES: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM_130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1. INTERVENTION: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism. OUTCOMES: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age. LESSONS: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors.

Spontaneous regression of gastric gastrinoma after resection of metastases to the lesser omentum: A case report and review of literature.

BACKGROUND: Gastric gastrinoma and spontaneous tumor regression are both very rarely encountered. We report the first case of spontaneous regression of gastric gastrinoma. CASE SUMMARY: A 37-year-old man with a 9-year history of chronic abdominal pain was referred for evaluation of an 8 cm mass in the lesser omentum discovered incidentally on abdominal computed tomography. The tumor was diagnosed as grade 2 neuroendocrine neoplasm (NEN) on endoscopic ultrasound-guided fine-needle aspiration. Screening esophagogastroduodenoscopy revealed a 7 mm red polypoid lesion with central depression in the gastric antrum, also confirmed to be a grade 2 NEN. Laparoscopic removal of the abdominal mass confirmed it to be a metastatic gastrinoma lesion. The gastric lesion was subsequently diagnosed as primary gastric gastrinoma. Three months later, the gastric lesion had disappeared without treatment. The patient remains symptom-free with normal fasting serum gastrin and no recurrence of gastrinoma during 36 mo of follow-up. CONCLUSION: Gastric gastrinoma may arise as a polypoid lesion in the gastric antrum. Spontaneous regression can rarely occur after biopsy.

[A case of difficult to diagnose duodenal gastrinoma].

A 42-year-old man, after remission of MALT lymphoma of the small intestine, was repeatedly hospitalized because of abdominal pain and severe dehydration caused by frequent vomiting and watery diarrhea. His symptoms would improve quickly every time when he was fasted and inserted a nasogastric tube. We were unable to find abnormalities on endoscopic examination and computed tomography. He was suspected to have gastrinoma because of active bleeding from a duodenal ulcer. High-level serum gastrin, endoscopic ultrasound, somatostatin receptor scintigraphy, and selective arterial calcium injection test were done. He was diagnosed with pancreatic gastrinoma in the pancreatic head by endoscopic ultrasound fine needle aspiration and subsequently underwent pancreatoduodenectomy. Histopathologic findings showed a 3-mm neuroendocrine tumor located in the duodenal submucosal layer. The presence of metastasis was confirmed in one of the peripancreatic lymph nodes. The pancreatic gastrinoma in the pancreatic head that we initially diagnosed was a lymph node metastasis behind the pancreas. Because additional resection was performed on the duodenum, we were able obtain a diagnosis of duodenal gastrinoma.

Primary lymph node gastrinoma: a case report and review of the literature.

BACKGROUND: Gastrinoma is a rare form of neuroendocrine neoplasm. The presence of a primary lymph node localization of gastrinoma is a much debated and controversial topic in the literature, as regards whether these cases represent metastatic disease from an as yet unidentified primary tumor, or the de novo occurrence of a gastrinoma in a lymph node. CASE PRESENTATION: We report the case of a 24-year-old male with intense epigastric pain treated at the beginning with high dose proton pump inhibitors. Further workup with CT and subsequent laparotomy revealed a single peripancreatic lymph node. Histological examination highlighted a well-differentiated neuroendocrine tumor. CONCLUSION: This case underlines that the primitive lymph node gastrinoma is a distinct nosological entity with a precise location in the context of rare neuroendocrine tumors that should be considered when specific symptoms are associated with the identification of isolated lymph nodes, after excluding any possible primitive locations of neoplastic localization.