Guideline sources The following summarized guidelines for the evaluation and management of multiple endocrine neoplasia type 1 are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2021; 2020), the American Association of Endocrine Surgeons (AAES 2016), the European Neuroendocrine Tumor Society (ENETS 2015), and the Endocrine Society (ES 2012). 1 2 3 4 5 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Diagnostic investigations Genetic testing: As per ESMO 2020 guidelines, obtain genetic testing in patients with multiple endocrine neoplasias (hyperparathyroidism and/or pituitary tumours), a family history of NETs or https://web.pathway.md/diseases/reciv94gkMzJpS9eA 1/5 6/30/23, 1:05 AM Multiple endocrine neoplasia type 1 Pathway associated diseases and features suspicious of a hereditary disease, as well as in young patients (< 40 years of age) with gastrinoma. B As per ENETS 2015 guidelines, obtain MEN1 gene mutation analysis in patients with a family history suggestive of a MEN1 or a second MEN1 feature. B As per ES 2012 guidelines, provide genetic counseling before obtaining mutation testing for MEN1. A Show 5 more 2. Medical management Setting of care: Manage patients with MEN1 and their families by a multidisciplinary team of relevant specialists with experience managing endocrine tumors. B Ensure a multidisciplinary team approach including specialist physicians (such as endocrinologists, gastroenterologists, and oncologists), endocrine surgeons, histopathologists (with expertise in NETs), radiologists (including those with expertise in nuclear medicine), and clinical geneticists in the management of patients with NETs. B Management of parathyroid tumors: As per AAES 2016 guidelines, perform subtotal parathyroidectomy as the index surgery in patients with MEN1-associated primary hyperparathyroidism. B As per ES 2012 guidelines, perform surgery by an experienced endocrine surgeon as the treatment of choice in patients with parathyroid tumors. Insufficient evidence to recommend an optimum timing for surgery. B Show 2 more Management of pituitary tumors: offer the same treatment (consisting of appropriate medical therapy, such as dopamine agonists for prolactinoma, octreotide or lanreotide for somatotrophinomas, or selective transsphenoidal surgical hypophysectomy with radiotherapy reserved for residual unresectable tumor tissue) in patients with MEN1-associated pituitary tumors as for patients with non-MEN1 pituitary tumors. A Management of pancreatic tumors: As per ESMO 2020 guidelines, offer a watch-and-wait management in patients with MEN1- associated nonfunctioning pancreatic NETs 2 cm in size. B As per ES 2012 guidelines, obtain full evaluation of the extent of disease before planning specific therapy in patients with pancreatic NETs. B Show 8 more Management of gastric tumors: consider obtaining endoscopic surveillance in patients with small (< 10 mm) gastric carcinoids. Perform endoscopic or local resection with partial or total gastrectomy in patients with larger tumors. Insufficient evidence to support the use of somatostatin analogs for type 2 gastric carcinoids. C Management of thymic/bronchopulmonary tumors: https://web.pathway.md/diseases/reciv94gkMzJpS9eA 2/5 6/30/23, 1:05 AM Multiple endocrine neoplasia type 1 Pathway Perform curative surgery, where possible, as the treatment of choice in patients with thymic and bronchial carcinoid tumors. A Consider offering radiotherapy and chemotherapy in patients with advanced diseases where curative surgery is impossible. C Management of adrenal tumors: offer the same treatment in patients with MEN1-associated adrenal tumors as for patients with non-MEN1 adrenal tumors. Perform surgery in patients with functioning tumors (such as primary hyperaldosteronism or hypercortisolism) and non-functioning tumors with atypical features, size > 4 cm, or significant growth over a 6-month interval. B 3. Follow-up and surveillance Surveillance for tumors, general principles: obtain regular screening (such as annually) for the development of MEN1-associated tumors in patients with positive MEN1 germline mutation. B Surveillance for tumors, parathyroid: obtain an annual assessment of plasma calcium and PTH concentrations to screen for primary hyperparathyroidism. A Surveillance for tumors, pituitary: Consider obtaining an annual assessment of plasma prolactin and IGF-1 levels C and MRI of the pituitary every 3-5 years, depending on clinical judgment and local resources. C Obtain hypothalamic pituitary testing in patients with abnormal results to further characterize the nature of the pituitary lesion and its effects on the secretion of other pituitary hormones. A Surveillance for tumors, pancreatic: obtain an annual plasma biochemical assessment of fasting gastrointestinal tract hormone profile, including measurement of gastrin, glucagon, vasointestinal polypeptide, pancreatic polypeptide, chromogranin A, and insulin with an associated fasting glucose level, as a minimum for screening of gastropancreatic NETs. B Show 2 more Surveillance for tumors, gastric: perform gastroscopic examination with biopsy every 3 years to detect peptic ulcer disease and gastric carcinoid type 2 in patients with hypergastrinemia. B Consider performing EUS and somatostatin receptor scintigraphy to aid in the diagnosis. A Surveillance for tumors, thymic/bronchopulmonary: As per ESMO 2021 guidelines, consider discussing prophylactic thymectomy in young male adult patients with MEN1 in families with aggressive thymic tumors. C As per ES 2012 guidelines: Obtain chest CT or MRI every 1-2 years to detect thymic and bronchopulmonary carcinoid tumors. B Do not obtain biochemical evaluation with urinary 5-HIAA or chromogranin A. D Surveillance for tumors, adrenal: Obtain abdominal CT or MRI every 3 years for surveillance. B Obtain radiological surveillance and assess for malignant features in patients with adrenal lesions. Review images by a radiologist with expertise in adrenal imaging. B https://web.pathway.md/diseases/reciv94gkMzJpS9eA 3/5 6/30/23, 1:05 AM Multiple endocrine neoplasia type 1 Pathway Obtain biochemical evaluation of adrenal lesions in patients with clinical features or tumors > 1 cm in size. Focus on assessment for primary hyperaldosteronism and primary hypercortisolemia. B Clinical findings Past medical history Lab findings Acromegaly ACTH Adrenocortical tumor blood glucose Bronchial tumor serum C-peptide Cushing's disease serum GH Gastrinoma serum IGF-1 Gigantism serum PTH Hyperthyroidism serum TSH Insulinoma serum aldosterone Parathyroid tumor serum calcium Pituitary tumor serum cortisol Prolactinoma serum gastrin Thymic tumor serum glucagon Thyrotropinoma serum insulin Vipoma serum proinsulin serum prolactin Imaging findings serum vasoactive intestinal peptide Adrenal mass blood glucose Lung mass Pancreatic mass Genetic testing Pituitary mass Men1 gene mutation Pulmonary nodules Thymic mass Diagnostic procedures secretin stimulation test References 1. Rajesh V Thakker, Paul J Newey, Gerard V Walls et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 MEN1 . J Clin Endocrinol Metab. 2012 Sep;97 9 2990 3011. Open 2. Scott M Wilhelm, Tracy S Wang, Daniel T Ruan et al. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016 Oct 1;151 10 959 968. Open https://web.pathway.md/diseases/reciv94gkMzJpS9eA 4/5 6/30/23, 1:05 AM Multiple endocrine neoplasia type 1 Pathway 3. E Baudin, M Caplin, R Garcia-Carbonero et al. Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021 Apr;32 4 439 451. Open 4. M E Caplin, E Baudin, P Ferolla et al. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015 Aug;26 8 1604 20. Open 5. M Pavel, K berg, M Falconi et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Jul;31 7 844 860. Open https://web.pathway.md/diseases/reciv94gkMzJpS9eA 5/5