[Gastroenteropancreatic neuroendocrine tumors : (GEP-NENs)]. / Neuroendokrine Neoplasien des Gastrointestinaltrakts : (GEP-NENs).

The entity of NENs represent a highly heterogenous group of malignancies that require a multidisciplinary approach during the treatment of patients. The following article aims to provide a concise overview of the current state of the art in diagnostics and therapy. One specific feature of G1/G2 NENs is that the indication for surgery is given even in metastatic settings. Specific details regarding the treatment of its various different subgroups need to be gathered from available guidelines or current clinical studies. The field of nuclear medicine offers promising options for diagnostics and therapy which needs further investigation.

Asymptomatic pheochromocytoma associated with MEN syndrome and subclinical Cushing's syndrome.

INTRODUCTION AND IMPORTANCE: Pheochromocytoma and Cushing's syndrome are rare endocrine conditions caused by tumors in the adrenal gland. These conditions are classified under Multiple Endocrine Neoplasia (MEN) syndrome, characterized by the development of multiple tumors in the endocrine system. However, diagnosing these conditions can be challenging as they often lack clear symptoms, requiring careful evaluation, monitoring, and treatment to prevent complications. CASE PRESENTATION: A 23-year-old male recently presented with right-sided abdominal fullness and lipoma-like masses on the torso. Over a span of six months, the abdominal mass nearly doubled in size, accompanied by elevated levels of catecholamines, cortisol, parathyroid hormone (PTH), and calcitonin. Surprisingly, the patient remained asymptomatic despite these abnormal lab values. CT imaging revealed a substantial increase in the size of the mass in the right adrenal gland, from 6 × 7 cm to approximately 11.2 × 10.2 × 9 cm. CLINICAL DISCUSSION: Pheochromocytoma secretes catecholamines and often leads to hypertension and related symptoms. Interestingly, most individuals with pheochromocytoma do not exhibit obvious symptoms, necessitating blood and urine tests, along with imaging studies, for accurate diagnosis. The size of the tumor does not necessarily indicate the severity of symptoms. MEN-2, a genetic syndrome, is characterized by pheochromocytoma, medullary thyroid carcinoma, and hyperparathyroidism. Additionally, methods for diagnosing Cushing's syndrome, caused by excess cortisol production, are discussed. CONCLUSION: Early diagnosis and genetic counseling are crucial in preventing complications associated with these conditions. By identifying them, appropriate treatment can be ensured for positive outcomes of patients and their families.

[MEN for multiple endocrin neoplasms: When evokate MEN? Update 2022]. / Mise au point sur les néoplasies endocriniennes multiples.

Multiple endocrine neoplasia (MEN) are genetic predisposition syndromes to endocrine tumors including MEN1, MEN2 and exceptionally MEN4. MEN are transmitted in an autosomal dominant fashion with a high penetrance. Classically, there is no genotype/phenotype correlation for NEM1 whereas this is the case for NEM2. Patients with NEM1, linked to an inactivating mutation of the menin gene, may present with: primary hyperparathyroidism, pituitary adenoma, duodeno-pancreatic neuroendocrine tumors (NETs), bronchial tumors with an increased risk of thymoma, adrenal cortical tumors, an increased risk of breast cancer and characteristic skin involvement such as collagenomas, lentiginomas and an increased risk of skin cancer. These patients require at least annual follow-up. Screening of children is proposed from the age of 5 years. Patients with NEM2, linked to an activating mutation of the RET proto-oncogene, all present with medullary thyroid carcinoma (MTC) at a variable age depending on the genotype. Some patients present a pheochromocytoma (50 %) and hyperparathyroidism (20 %). Pediatric forms with aggressive CMT, ganglioneuromatosis and marfanoid syndrome exist (rare NEM2B). Some mutations are associated with a risk of aggressive CMT, justifying prophylactic thyroidectomy before 6 months of age. The age of genetic testing depends on the mutation subtype in the NEM2 parent. NEM4, related to a mutation in the CDKN1B gene, are rare, with a less well-known pathogenesis and their follow-up is not well codified.

Hereditary Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a commonly encountered clinical problem and occurs as part of an inherited disorder in ∼10% of patients. Several features may alert the clinician to the possibility of a hereditary PHPT disorder (eg, young age of disease onset) whilst establishing any relevant family history is essential to the clinical evaluation and will help inform the diagnosis. Genetic testing should be offered to patients at risk of a hereditary PHPT disorder, as this may improve management and allow the identification and investigation of other family members who may also be at risk of disease.

Advances in the diagnosis and the management of primary hyperparathyroidism.

The parathyroid glands, one of the last organs to be discovered, are responsible for maintaining calcium homeostasis, and they continue to present the clinician with diagnostic and management challenges that are reviewed herein. Primary hyperparathyroidism (PHPT) comprises the vast majority of pathology of the parathyroid glands. The classic variant, presenting with elevated calcium and parathyroid hormone levels, has been studied extensively, but the current body of literature has added to our understanding of normocalcemic and normohormonal variants of PHPT, as well as syndromic forms of PHPT. All variants can lead to bone loss, kidney stones, declining renal function, and a variety of neurocognitive, gastrointestinal, and musculoskeletal complaints, although the majority of PHPT today is asymptomatic. Surgery remains the definitive treatment for PHPT, and advances in screening, evolving indications for surgery, new imaging modalities, and improvements in intra-operative methods have greatly changed the landscape. Surgery continues to produce excellent results in the hands of an experienced parathyroid surgeon. For those patients who are not candidates for surgery, therapeutic advances in medical management allow for improved control of the hypercalcemic state. Parathyroid cancer is extremely rare; the diagnosis is often made intra-operatively or on final pathology, and recurrence is common. The mainstay of treatment is normalization of serum calcium via surgery and medical adjuncts.

Multiple Endocrine Neoplasia Syndromes from Genetic and Epigenetic Perspectives.

Multiple endocrine neoplasia (MEN) syndromes are infrequent inherited disorders in which more than one endocrine glands develop noncancerous (benign) or cancerous (malignant) tumors or grow excessively without forming tumors. There are 3 famous and well-known forms of MEN syndromes (MEN 1, MEN 2A, and MEN 2B) and a newly documented one (MEN4). These syndromes are infrequent and occurred in all ages and both men and women. Usually, germ line mutations that can be resulted in neoplastic transformation of anterior pituitary, parathyroid glands, and pancreatic islets in addition to gastrointestinal tract can be an indicator for MEN1. The medullary thyroid cancer (MTC) in association with pheochromocytoma and/or multiple lesions of parathyroid glands with hyperparathyroidism can be pointer of MEN2 which can be subgrouped into the MEN 2A, MEN 2B, and familial MTC syndromes. There are no distinct biochemical markers that allow identification of familial versus nonfamilial forms of the tumors, but familial MTC usually happens at a younger age than sporadic MTC. The MEN1 gene (menin protein) is in charge of MEN 1 disease, CDNK1B for MEN 4, and RET proto-oncogene for MEN 2. The focus over the molecular targets can bring some hope for both diagnosis and management of MEN syndromes. In the current review, we look at this disease and responsible genes and their cell signaling pathway involved.

Medullary Thyroid Carcinoma: Prognostic Variables And Tumour Markers Affecting Survival.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy and its clinical course varies among patients due to its familial association. A number of prognostic factors have been studied, but the significance of these factors remains controversial. We evaluated the progression free survival (PFS) and overall survival (OS) of MTC and its association with tumour marker rising velocity and serum calcitonin (Ct) doubling time (DT). METHODS: Analysis of 83 (8.7%) consecutive MTC patients registered at a single centre between 1995 and 2015. The impact of tumour respectability, TNM stage, multiple endocrine neoplasia (MEN) syndrome, local recurrence, Ct DT and Ct rising velocity on PFS and OS was analysed. Median follow-up was 4.3 years (range: 1-18 years). RESULTS: Eighty-three (8.7%) of all thyroid cancers registered at our centre were MTC. Fifty-five males, 28 females. Mean age 39 years [range: 17-72 years]. Twenty-two were unresectable and 61 resectable. Five-year and 10-year OS was 84% and 77% respectively. Of 68 with follow up greater than a year; 20 (29.4%) were cured, 15 (22.1%) had biochemical evidence of disease, three (4.4%) had stable macroscopic disease and 30 (44.1%) had recurrent/progressive disease. Sixteen (23.5%) died. On multivariate analysis, T4 tumour, male gender, nodal and distant metastases, tumour resectibility, Ct DT less than two years and tumour marker rising velocity of greater than 0.05pg/ml/month were poor prognostic factors (pvalue <0.05). Age and association with MEN syndrome had no statistically significant survival impact. Radiotherapy reduced local relapse in patients with nodal disease. Total thyroidectomy with nodal clearance lessened relapses. CONCLUSION: Clinical stage and pathological aspects are predictors of disease progression. Persistent biochemical evidence of MTC does not affect OS, however, Ct DT < 2 years and rapid rate of tumour marker rise predict disease progression.

Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications relevant to the new American Thyroid Association guidelines.

BACKGROUND: The 2016 American Thyroid Association guidelines recommend multiple endocrine neoplasia testing and evaluation for pheochromocytoma before thyroidectomy after a thyroid fine-needle aspiration biopsy (FNA) is positive for medullary thyroid carcinoma (MTC). In the current study, the authors examined the reasons why FNA was unable to definitively diagnose MTC preoperatively, with attention to morphologic patterns that can be misleading. METHODS: Cases of MTC diagnosed on thyroid surgical resection for which there was a prior FNA and slides available for review were included (28 cases). Clinicopathologic data were collected. Slides were reviewed for numerous features blinded to the original FNA interpretation. Morphologic features were compared between concordant cases (20 cases) ("positive for MTC" or "suspicious for MTC") and discordant cases (4 cases) (any other interpretation). Three cases of microscopic MTC (measuring <1 cm) were excluded from statistical analysis, as was 1 case of sampling error (benign thyroid tissue). RESULTS: Nine men and 19 women were diagnosed with MTC. Four patients ultimately were diagnosed with multiple endocrine neoplasia, and 1 had bilateral pheochromocytomas. At the time of surgical excision, the mean tumor size was 2.3 cm (range, 0.1-7.5 cm). Review of morphologic features demonstrated that the discrepant cases were significantly more likely to have limiting factors (air-drying artifact/excess blood), a cohesive pattern, or to lack plasmacytoid morphology. None of the discordant cases had pseudoinclusions or amyloid (finding was not statistically significant). CONCLUSIONS: The majority (86%) of thyroid FNAs from patients with MTC are concordant (positive/suspicious for MTC). Patterns of failure include sampling error and limited typical morphologic features, particularly a lack of plasmacytoid morphology and cellular dyshesion. A high level of suspicion for MTC is critical to ensure patients receive appropriate preoperative testing. Cancer Cytopathol 2018;126:397-405. © 2018 American Cancer Society.

Sensor-augmented CSII therapy with predictive low-glucose suspend following total pancreatectomy.

Pancreatogenic diabetes is characterised by recurrent severe hypoglycaemia due to changes in both endocrine and exocrine functions. There are no guidelines to manage these individuals. Herein, we describe the post-operative management of two people who developed pancreatogenic diabetes following total pancreatectomy for neuroendocrine malignancy. In both individuals, diabetes was managed using sensor-augmented predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII). We demonstrate the benefit of sensor-augmented CSII in averting hypoglycaemia whilst optimising glycaemic control. Expected rates of severe hypoglycaemia in individuals with pancreatogenic diabetes can be averted with the use of continuous glucose monitoring (CGM) technology, optimising quality of life and reducing the risk of diabetes-related complications. LEARNING POINTS: There are no clear guidelines to manage people with pancreatogenic diabetes.We describe the use of CGM with predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII) in the management of two individuals post-pancreatectomy.Predictive low-glucose suspend technology can achieve excellent glycaemic control whilst avoiding recurrent and severe hypoglycaemia in people with pancreatogenic diabetes.Predictive low-glucose suspend CGM should be considered as an effective therapeutic option for the management of pancreatogenic diabetes.

Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis.

BACKGROUND: The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. METHODS: We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. RESULTS: The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. CONCLUSION: Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1881-E1885, 2016.

An unusual cause of hemoperitoneum: case report with review of literature.

Spontaneous hemoperitoneum (SH) is a rare entity which can be life-threatening. Gastrointestinal neurofibromas are rare. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. The clinical presentations of isolated neurofibromatous lesions of the intestines are variable. In asymptomatic patient no treatment may be required and patient may be kept on follow up. Occasionally, they manifest with complications such as intestinal bleeding, obstruction or perforation. Surgery is the treatment of choice in symptomatic intestinal neurofibroma. We present the case of a 55 year-old male with acute abdomen due to rupture of isolated neurofibroma as one of the cause of SH. This case represents a rare presentation of isolated intestinal neurofibromatosis in a patient without systemic manifestations and highlights the need for high index of suspicion to exclude neurofibromatosis type 1 or multiple endocrine neoplasia type 2b.

Laparoscopic Pylorus- and Spleen-Preserving Duodenopancreatectomy for a Multifocal Neuroendocrine Tumor.

BACKGROUND: In contrast to laparoscopic left pancreatic resection, laparoscopic total duodenopancreatectomy is a procedure that has not been standardized until now. It is not only the complexity that limits such a procedure but also its rare indication. The following article demonstrates the technical aspects of laparoscopic pylorus- and spleen-preserving duodenopancreatectomy. CASE REPORT: The indication for intervention in the underlying case was a patient diagnosed with a multiple endocrine neoplasia (MEN) I syndrome and a multifocal neuroendocrine tumor (NET) infiltrating the duodenum and the pancreas. The patient was post median laparotomy which was necessary after jejunal perforation due to a peptic ulcer. The resection was carried out entirely laparoscopically, and the reconstruction, which included a biliodigestive anastomosis and a gastroenterostomy, was carried out by means of a median upper abdomen laparotomy of 7 cm in length through which the resected specimen was also removed. The total operative time was 391 min. The blood loss accounted for 250 ml. The postoperative course was uneventful, and the patient was discharged on the eighth postoperative day. CONCLUSION: Laparoscopic pancreatectomy is a treatment option in carefully selected indications. The complexity of the operation demands a high level of expertise in the surgical team.

Simultaneous bilateral laparoscopic adrenalectomy for pheochromocytoma in multiple endocrine neoplasia (MEN) syndrome: Case report with review literature.

INTRODUCTION: Laparoscopic adrenalectomy has gained favour as a preferred surgical approach in the multiple endocrine neoplasia (MEN) type 2 patients. Currently, there is limited literature on bilateral simultaneous laparoscopic adrenalectomy in MEN 2 syndrome. We reported two cases of bilateral pheochromocytoma associated with MEN 2 syndrome cured by simultaneous bilateral laparoscopic adrenalectomy. PRESENTATION OF CASE: First patient presented with big lips since childhood and episodic abdominal pain. On investigations, he was diagnosed with features of MEN 2B syndrome. Second patient was hypertensive and presented with abdominal pain. On evaluation she had features of MEN 2A syndrome. DISCUSSION: Minimally invasive approach was preferred in both cases. Bilateral simultaneous adrenalectomies were uneventfully done with acceptable operative time and blood loss with rapid perioperative recovery. These cases highlighted the feasibility of laparoscopic simultaneous bilateral adrenalectomy for pheochromocytomas in MEN 2 syndrome. CONCLUSION: Laparoscopic simultaneous bilateral adrenalectomy is a safe feasible and preferable technique for pheochromocytomas associated with MEN 2 syndrome.

Gastric carcinoid tumors.

Initially, carcinoid tumors were a curiosity for physicians and were so named because of their relatively benign behavior as compared to the more common adenocarcinomas. As medicine has evolved, our understanding and management have greatly improved. Our classification system has also become more specific. Gastric carcinoid tumors are unique in that three types have been described based upon each one's pathophysiology. In general, none of these give rise to the typical carcinoid syndrome as seen with metastatic ileal carcinoids.Type 1 gastric carcinoids represent 70% to 80% and are characterized by multiple small lesions and their association with hypergastrinemia secondary to chronic atrophic gastritis and pernicious anemia, and are less likely to metastasize. Type 2 is a rare entity, representing 5%, and is characterized by multiple small lesions, hypergastrinemia secondary to Zollinger-Ellison syndrome, and multiple endocrine neoplasia (MEN) type 1. The risk for metastasis is slightly higher than for type 1; however, overall prognosis is dependent upon the gastrinoma prognosis. Accounting for 20%, type 3 is known as sporadic gastric carcinoids in that there is no association with hypergastrinemia, chronic atrophic gastritis, or Zollinger-Ellison syndrome. These present as large solitary lesions and are often metastatic upon diagnosis. A unique feature of type 3 is its association with an atypical carcinoid syndrome that is thought to be mediated by histamine.The treatment-including medical, endoscopic, and surgical-of gastric carcinoids is dictated by the type, size, and presence of metastasis.