endocrine and metabolic disorders
Multiple Endocrine Neoplasia, Type 1 (MEN 1)
Diagnosis of MEN 1
Serum calcium,parathyroid hormone(PTH), gastrin, and prolactin levels Tumor localization with MRI, CT, ultrasonography, or 18F-FDG PET/CT Genetic testing MEN 1 syndrome should be considered in patients with tumors of the parathyroids, pancreas, or pituitary, particularly those with a family history of endocrinopathy. MEN 1 should also be considered in individuals diagnosed with hyperparathyroidism prior to age 30 years ( Diagnosis references ). At-risk individuals should undergo genetic testing with direct DNA sequencing of a panel of genes that may cause MEN 1 or related syndromes, including MEN 4 and other forms of familial hyperparathyroidism (eg,CDC73-related disorders, which may include the rare syndrome of hyperparathyroidism and jaw tumors). All of these individuals should also undergo clinical screening for other tumors of MEN 1, including evaluation for the following: Symptoms of Peptic Ulcer Disease , diarrhea, Visual field defects, Prolactinoma , and features of Abnormal levels of serum calcium, intact PTH, gastrin, and prolactin Additional laboratory or radiologic tests should be done if these screening tests suggest an endocrine abnormality related to MEN 1. A gastrin-secreting gastroenteropancreatic neuroendocrine (GEP-NET) tumor of the pancreas or duodenum is diagnosed by elevated basal plasma gastrin levels, an exaggerated gastrin response to infused calcium, and a paradoxical rise in gastrin level after infusion ofsecretin. Aninsulin-secreting beta-cell tumor of the pancreas is diagnosed by detecting fasting hypoglycemia with an elevated plasmainsulinlevel. An elevated basal level of pancreatic polypeptide or gastrin or an exaggerated response of these hormones to a standard meal may be the earliest sign of pancreatic involvement. Gigantism and Acromegaly is diagnosed by elevated growth hormone levels that are not suppressed by glucose administration and by elevated levels of serum positron emission tomography (PET)/CT may be useful in distinguishing bronchopulmonary neuroendocrine tumors from benign pulmonary nodules and in identifying thymic carcinoid ( Diagnosis references ). For pancreatic and duodenal neuroendocrine tumors, When an index case is identified, 1st-degree relatives should be given the option of genetic screening. Family members can also be screened biochemically by measurement of calcium and PTH, which is frequently useful because of the high penetrance of hyperparathyroidism in MEN 1. Although early presymptomatic screening of family members of patients with MEN 1 has not been shown to reduce morbidity or mortality, a large cohort study reported a significant lag time between diagnosis of the index case and diagnosis in the rest of the family. This lag was found to be clinically relevant, because patients diagnosed after a preventable delay were found to have a higher incidence of pancreatic tumors, including metastatic lesions ( Diagnosis references ). Preimplantation genetic diagnosis on embryos conceived via Assisted Reproductive Techniques is also available. Some clinicians monitor gene carriers by doing pancreatic and pituitary imaging every 3 to 5 years, although such screening has not been shown to improve outcomes. Breast Cancer Screening and Prevention is recommended beginning at age 40 in women with MEN 1 ( 1.Thakker RV, Newey PJ, Walls GV, et al: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1).J Clin Endocrinol Metab97(9):2990–3011, 2012. 2.So A, Pointon O, Hodgson R, Burgess J: An assessment of 18 F-FDG PET/CT for thoracic screening and risk stratification of pulmonary nodules in multiple endocrine neoplasia type 1.Clin Endocrinol(Oxf) 88(5):683–691, 2018. 3.Sadowski SM, Millo C, Cottle-Delisle C, et al: Results of (68)Gallium-DOTATATE PET/CT scanning in patients with multiple endocrine neoplasia type 1.J Am Coll Surg22:509–517, 2015. 4.van Leeuwaarde RS, van Nesselrooij BP, Hermus AR, et al. Impact of delay in diagnosis in outcomes in MEN1: Results from the Dutch MEN1 Study Group.J Clin Endocrinol Metab101(3):1159–1165, 2016. 5.de Laat JM, van Leeuwaarde RS, Valk GD: The importance of an early and accurate MEN1 diagnosis.Front Endocrinol2018; doi.org/10.3389/fendo.2018.00533 6.van Leeuwaarde RS, Dreijerink KM, Ausems MG, et al: MEN1-dependent breast cancer: indication for early screening? Results from the Dutch MEN1 Study Group.J Clin Endocrinol Metab102:2083–2090, 2017. 