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Last updated: 11/17/2023
Years published: 2009, 2012, 2015, 2018, 2023
NORD gratefully acknowledges Maria Luisa Brandi, MD, PhD, Director of the Donatello Bone Clinic Villa Donatello Hospital, Sesto Fiorentino, Italy; President of the Fondazione F.I.R.M.O. Onlus (Fondazione Italiana per la Ricerca sulle Malattie dellโOsso) Florence, Italy; Scientific President of the Italian Association for Multiple Endocrine Neoplasia type 1 and 2 (AIMEN 1 e 2 โ ONLUS), and President of the Conferences International on Multiple Endocrine Neoplasia, for assistance in the preparation of this report.
Multiple endocrine neoplasia (MEN) type 1 is a rare genetic disorder characterized by multiple tumors arising from cells of specific neuroendocrine tissues. The endocrine system is the network of glands that secrete hormones into the bloodstream to reach their target organs along the entire body. These hormones regulate the chemical processes (metabolism) that influence the function of various organs and activities within the body. Hormones are involved in numerous vital and metabolic processes, including regulating heart rate, body temperature and blood pressure, as well as cell differentiation and growth.
In individuals with MEN type 1, tumors develop in multiple endocrine glands, principally the parathyroids, gastro-entero-pancreatic tract and anterior pituitary gland. These affected glands secrete excessive amounts of hormones into the bloodstream, which can result in a variety of symptoms and related syndromes. Some tumors associated with MEN type 1 are cancerous (malignant) (i.e., gastrinomas and carcinoids) and can spread to other organs (metastasize). Other, less frequent, features of the MEN1 syndrome are neuroendocrine tumors of thymus and bronchi, adrenocortical tumors, lipomas, visceral leiomyomas, truncal and facial collagenomas, facial angiofibroma, breast carcinoma, meningioma and ependymomas. MEN type 1 can run in families, in which the causative gene variant is inherited from an affected parent, or it can occur, in extremely rare cases, as the result of a newly developed gene variant in the affected person.
MEN type 1-associated symptoms depend on which glands are affected by the overgrowth of tissue (hyperplasia) or tumor formation. Although most tumors are benign (noncancerous), tissue overgrowth or tumor formation causes the affected glands to become hyperactive and produce excess hormones. Elevated hormone levels are the main cause of MEN type 1-associated signs and symptoms. Certain tumors, such as gastrinomas and carcinoid tumors can potentially become malignant, and they still represent the two main causes of MEN type 1-associated death. The clinical expression of MEN type 1 is highly variable even within members of the same family and identical twins.
More than 20 different endocrine and non-endocrine tumors have been identified in individuals with MEN type 1. Affected individuals will not necessarily develop tumors at the same age or in the same locations and, therefore, they can manifest variable clinical signs and symptoms during their lifetime. Some individuals may only develop mild symptoms; others may develop serious, life-threatening complications. Some individuals may develop symptoms as young adults or adolescents; others may not develop symptoms until middle-age or older. It is important to note that individual cases are highly variable and that affected individuals will not develop all the symptoms discussed below.
PARATHYROID GLANDS
The most common affected endocrine glands in MEN type 1 are parathyroids, both as multiglandular hyperplasia and/or adenomas. Parathyroid glands are generally represented by four very small glands (approximately the size of a pea) located in the neck that secrete parathyroid hormone (PTH), which controls the serum calcium level. Hyperparathyroidism is the medical term indicating a constantly high level of circulating PTH. More than 90 percent of individuals with MEN type 1 develop, by age 50, primary hyperparathyroidism (PHPT) due to PTH hyperproduction by the affected parathyroid gland(s). The mean age of onset is the third decade of life. In some people, hyperparathyroidism may be detected during adolescence and infancy (by the age of 5). PHPT is the first sign of MEN type 1 in about 90% of patients.
PHPT can be very mild and may not cause any obvious symptoms (asymptomatic). Untreated hyperparathyroidism generally results in elevated serum level of calcium (hypercalcemia), which can cause kidney stones or damage the kidneys. Hyperparathyroidism can cause additional symptoms in some people, including fatigue, weakness, constipation, nausea, ulcers, indigestion, high blood pressure (hypertension) and muscle or bone pain. Central nervous system abnormalities can eventually develop including mental status changes, lethargy, depression and confusion, as a consequence of severe hypercalcemia. Some individuals may develop abnormal thinning of bones (osteoporosis), which can result in an increased risk of fragility fractures. Most individuals with hyperparathyroidism do not develop all these symptoms, especially when the condition is diagnosed early and treated.
PANCREAS AND DUODENUM
Duodeno-pancreatic neuroendocrine tumors occur in over 80% of MEN type 1 patients. The pancreas is a small gland located behind the stomach. It contains specialized endocrine cells called islet cells, which secrete several hormones including insulin (which lowers blood sugar levels), glucagon (which raises blood sugar levels) and hormones that travel to the intestines and aid in digestion such as gastrin. The duodenum is the first portion of the small intestine, which connects the intestines to the stomach.
Approximately 40 percent of adults with MEN type 1 develop multiple gastrinomas, usually located in the first portion of duodenum, and more rarely in the pancreas. Approximately, 50% of MEN1-gastrinomas have already metastasized at the time of clinical diagnosis. Gastrinomas are functioning tumors that secrete gastrin. Elevated levels of gastrin induce the stomach to release too much acid, which, in turn, can result in abdominal pain, diarrhea, backflow of the contents of the stomach into the esophagus (esophageal reflux) and peptic ulcers. Peptic ulcers are open sores lining the stomach, esophagus, and intestines. Peptic ulcers can cause a burning pain in the stomach, diarrhea, nausea, vomiting and fatty, smelly stools. In severe cases, peptic ulcers can cause serious complications including internal bleeding, vomiting up of blood, obstruction of the passage of food through the digestive tract (gastric outlet obstruction) or the development of a hole in the wall of the stomach or small intestines (perforation), allowing the contents of the stomach or intestines to leak into the abdomen. Less common symptoms associated with gastrinomas include unintended weight loss and heartburn. Gastrinomas and other tumors that arise from islet cells can potentially become malignant and spread (metastasize) to other areas of the body, especially nearby lymph nodes and the liver.
Multiple gastrinomas are also found in a non-syndromic disorder called Zollinger-Ellison syndrome, which usually occurs randomly for unknown reasons.
Additional tumors can affect the pancreas in MEN type 1. Among them, insulinoma, a functioning benign tumor that secretes insulin, is the second most common tumor affecting the endocrine pancreas, occurring in approximately 10 percent of individuals with MEN type 1. Insulinoma can cause low blood sugar (hypoglycemia), especially when not eating over a period of time (fasting). Hypoglycemia can cause a variety of symptoms including confusion, abnormal behavior, blurred vision, double vision, anxiety, heart palpitations, sweating and hunger.
Tumors that secrete too much glucagon or somatostatin (respectively named glucagonomas and somatostatinomas) can also occur in the pancreas islet of MEN type 1 patients, in a lesser percentage. These tumors result in elevated levels of blood sugar (hyperglycemia). Hyperglycemia can cause diabetes.
In rare cases, individuals with MEN type 1 can develop a VIPoma, a tumor that secretes a hormone called vasoactive intestinal peptide (VIP). VIPomas can cause chronic, watery diarrhea and eventually cause dehydration.
In approximately 40 percent of patients, non-functioning pancreatic tumors, often multiple, small and scattered to the entire organ, may occur. They do not secrete any active hormone and are not related to the occurrence of any endocrine syndrome. Non-functioning pancreatic tumors may have a malignant potential, mainly for tumors larger than 2 cm in diameter.
PITUITARY GLAND
Approximately 25 percent of individuals with MEN type 1 develop benign adenoma of the anterior pituitary gland. The pituitary is a small pea-sized gland that sits in the base of brain and is sometimes called โthe master glandโ because it oversees the function of most of the endocrine glands in the body. The pituitary gland secretes a variety of different hormones including prolactin, which influences fertility and stimulates breast milk production; growth hormone, which regulates body growth especially during adolescence; and several hormones that stimulate the activity of other glands including the adrenal and thyroid glands and ovaries and testes.
In some MEN1 patients, symptoms of pituitary gland involvement may be the first sign of the disorder. Benign tumors that secrete prolactin (prolactinomas) are the most common pituitary gland tumors associated with MEN type 1. They are the third most common tumors associated with MEN type 1 after parathyroid tumors and gastrinomas. In females, prolactinomas can cause irregular menstrual periods (oligomenorrhea to amenorrhea), infertility, diminished sexual drive, painful intercourse and the production of breast milk in females who are not pregnant (galactorrhea). The most common clinical manifestations in males are impotence and gynecomastia.
Pituitary tumors, especially when more than 1 centimeter in diameter (macrodenoma), can result in additional symptoms because they can apply pressure upon other tissues of the brain. Resulting symptoms may include headaches and visual problems, such as blurred vision.
In addition to prolactinoma, other tumors affecting the pituitary gland may occur. One of these tumors can secrete excess growth hormone resulting in a condition characterized by excessive bone growth and enlargement of certain structures of the body such as the jaw, hands and feet (acromegaly) in post-puberal patients. Another of these tumors may secrete adrenocorticotrophin (ACTH), a hormone that stimulates the adrenal glands, which results in excessive corticosteroid production. Excessive corticosteroid levels can eventually cause a condition called Cushingโs syndrome which is characterized by a wide variety of signs and symptoms including a rounded face (moon face), increased fat around the neck, weight gain around the midsection and upper back, muscle weakness, fatigue and high blood pressure.
ADRENAL GLAND TUMORS
The adrenal glands are located on top of the kidneys and are constituted by cortex and medulla. Both adrenal cortex and adrenal medulla secrete hormones to regulate the functions of the body; the cortex produces steroid hormones (glucocorticoids, mineralocorticoids, and adrenal androgens), while the medulla produces the catecholamines (epinephrine, and norepinephrine).
In approximately 20-40% of patients with MEN1, non-functioning tumors of the adrenal glands may occur. In rare cases, functioning adrenal gland tumors of the cortex result in the overproduction of corticosteroid hormones and the development of Cushingโs syndrome. In extremely rare cases, about 1%, a pheochromocytoma (PHEO) may occur in an individual with MEN type 1. Most PHEOs originate in the inner layer (medulla) of one of the two adrenal glands. Symptoms may include high blood pressure, headaches, excessive sweating and heart palpitations. PHEOs occur much more often in individuals with multiple endocrine neoplasia type 2.
CARCINOID TUMORS
Approximately 10-15% of individuals with MEN type 1 develop slow-growing carcinoid tumors. These tumors usually develop in the stomach (gastric carcinoids), bronchial tubes (bronchial carcinoids) and the thymus (thymic carcinoids), a small gland located in the upper chest just behind the breastbone. Carcinoid tumors of the bronchial tubes primarily affect females; carcinoid tumors of the thymus primarily affect males. Gastric carcinoids may usually develop in MEN type 1 patients affected by ZES, and since hypergastrinemia is a promoter for gastric carcinoid proliferation, the best method for preventing the development of these tumors is the surgical resection of gastrinoma.
In most patients, these tumors do not produce hormones (non-functioning tumors) and usually do not cause any symptoms (asymptomatic), but they can present a rapid growth and malignant progression being responsible for some MEN1-asscociated deaths. In rare cases, carcinoid tumors may overproduce different hormones including ACTH, calcitonin, growth hormone releasing hormone (GHRH), serotonin and histamine. When carcinoid tumors secrete serotonin, they can cause carcinoid syndrome, a condition characterized by migraines, diarrhea and episodes of feeling flushed.
Carcinoid tumors associated with MEN type 1 are usually identified later during life, with a mean diagnosis of age 50. These tumors may be benign, but malignant (cancerous) carcinoids can develop. Thymic carcinoids associated with MEN type 1 may be particularly aggressive, especially in male smokers.
NON-ENDOCRINE BENIGN TUMORS
Several tumors that do not arise from endocrine cells may also occur in individuals with MEN type 1. The most common is lipoma, a benign tumor consisting of fat cells. Lipomas usually develop just under the surface of the skin and are common in the general population. Multiple lipomas often form. Lipomas are not usually associated with any symptoms. Some individuals with MEN type 1 may also develop benign raised, reddish spots on the face (angiofibroma) and benign, raised, whitish spots on the skin (collagenomas).
Less common, non-endocrine, benign tumors associated with MEN type 1 include tumors arising from the membranes (meninges) lining the brain and spinal cord (meningioma), tumors arising from smooth muscle cells (leiomyoma) and tumors arising from central nervous system tissue (ependymomas). These tumors generally do not cause any symptoms.
MEN type 1 is a rare genetic disorder caused by loss-of-function variants of the MEN1 gene. The MEN1 gene encodes a nuclear protein known as menin. The exact role of menin is not fully understood. The MEN1 gene is a tumor suppressor gene, a gene that when it operates normally may have several functions including inhibiting cell division, repairing and replicating DNA and instructing cells when to die (a normal process called apoptosis). When tumor suppressor genes malfunction, certain cells may continue to grow and reproduce causing tumor formation.
MEN type 1 follows autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
MEN type 1 affects males and females in equal numbers. It affects approximately 1 in 30,000 individuals. Some researchers think that many cases of MEN type 1 go undiagnosed, making it difficult to determine its true frequency in the general population. The onset of the disorder can vary widely, and it has been identified in children as young as 5 and adults as old as 80. MEN type 1 was first recognized as a genetic disorder in 1954.
Affected individuals may receive a diagnosis of MEN type 1 following a thorough clinical evaluation, a detailed patient and family history and the identification of at least two of the three characteristic endocrine tumors associated with the disorder (i.e., parathyroid and pituitary tumors and islet cell tumors in the pancreas or duodenum). Individuals with only one of the associated tumors and a positive family history of the disorder may also receive a diagnosis of MEN type 1. A variety of tests to detect elevated levels of certain hormones in the blood may be necessary to aid in the early identification of tumors. For example, identification of elevated levels of PTH together with hypercalcemia can indicate the presence of a parathyroid tumor. A variety of imaging scans may be performed to aid in identifying the size and location of specific tumors.
A diagnosis of MEN type 1 can be confirmed through genetic testing of the MEN1 gene, which can reveal the characteristic variants of the MEN1 gene that causes the disorder. Individual clinical manifestations cannot be foreseen by the result of the genetic analysis (No direct genotype-phenotype correlation exists.). The identification of an inactivating MEN1 gene variant is a genetic diagnosis of the syndrome, and all individuals with a disease-causing variant will have symptoms by age 55.
Treatment
The treatment of MEN type 1 may require the coordinated efforts of a team of specialists. Endocrinologists, surgeons, cancer specialists (oncologists), and other healthcare professionals may need to plan a patientโs treatment systematically and comprehensively. Treatment is directed toward the specific symptoms that are apparent in each individual and may include drugs to counteract the effects of excess hormones, surgical removal of tumors or, medical therapies, such as SSAs, peptide receptor radionuclide therapy (PRRT), cytotoxic chemotherapy (i.e. streptozocin and 5-fluorouracil, doxorubicin, temozolomide with capecitabine), inhibitors of thyrosin kinase receptors (i.e. sunitinib), inhibitors of mammalian target of rapamycin (mTOR; i.e. everolimus) and rarely radiation therapy or stereotaxic radiosurgery to help shrink or destroy tumors.
Specific therapeutic procedures and interventions may vary depending upon numerous factors, such as primary tumor location; the size and type of tumor; the severity of symptoms due to excess hormone production; whether malignant tumors are present and whether they have spread to lymph nodes or distant sites; individualโs age and general health; and/or other elements. Decisions concerning the use of interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of their case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.
The main treatment for parathyroid tumors is surgery, although the best type of surgery and the best time for surgery is still controversial. Surgical removal of the parathyroid glands is called a parathyroidectomy. One approach is to remove three parathyroid glands entirely and a portion of the fourth (subtotal parathyroidectomy). There is a 50 percent risk of recurrence of a parathyroid tumor with this method. Another approach is to remove all four glands (total parathyroidectomy). This procedure is usually followed by the transplantation of some of the apparently healthy parathyroid tissue into another area of the body (usually the nondominant forearm). Because of the high risk of disease recurrence, this would spare affected individuals from being operated on in the same area (i.e., the neck). In some cases, healthy parathyroid tissue is saved through cryopreservation (the process of cooling and storing tissue) and re-implanted later. Nonsurgical option in the treatment of MEN1-associated primary hyperparathyroidism is cinacalcet, a calcium agonist drug (calcimimetics), in patients who do not meet the criteria for parathyroidectomy, for those who failed a previous intervention, or for those presenting recurrence who do not want to undergo any further surgical interventions.
Surgical removal of part or all of the parathyroid glands may result in hypoparathyroidism (low levels of parathyroid hormones and calcium in the blood). Affected individuals may require daily supplementation of calcium and active vitamin D to prevent the effects of hypoparathyroidism.
Pituitary tumors that secrete prolactin (prolactinomas) may be treated with dopamine agonists, drugs that lower the levels of prolactin in the blood and shrink pituitary tumors. Some prolactinomas are small enough that no therapy is required. In cases where drug therapy is ineffective or cannot be tolerated, trans-sphenoidal surgery (procedure in which surgeons go through the cavity (sphenoid sinus) directly behind the nose) may be required.
Pituitary tumors that produce ACTH are usually treated by transsphenoidal surgery. In cases of persistent hypercortisolism after surgery the medical therapies used provide adrenal steroidogenesis inhibitors such as ketoconazole and metyrapone.
Pituitary tumors that produce GH are treated by transsphenoidal surgery. In patients with postoperative active disease pharmacological treatment includes SSAs (octreotide, lanreotide and pasireotide), dopamine agonist (cabergoline) and GH receptor antagonist (pegvisomant).
In all pituitary tumors stereotaxic radiosurgery can be used when medical therapy is unavailable, unsuccessful or not tolerated.
The main objective of drug treatment for tumors that secrete gastrin (gastrinomas) is to reduce and control gastric acid hypersecretion with histamine-2 receptor antagonists (cimetidine, ranitidine, famotidine), proton pump inhibitors (PPIs; omeprazole, lansoprazole, pantoprazole) or somatostatin analogues (SSAs; octreotide and lanreotide). SSAs also have an effect in reducing tumor size.
Timing and type of surgery for gastrinoma [i.e., Thompson procedure (i.e., wide longitudinal duodenotomy with excision of duodenal gastrinomas and of peri-pancreatic lymph nodes, pancreatoduodenectomy; PD), or duodenectomy with reimplants of the papilla] are still controversial and usually are chosen according to the characteristics of the patient.
Insulinomas are usually surgically removed through enucleation of the greatest pancreatic lesions or distal pancreatic resection preserving splenic vessels and spleen. If the tumor cannot be completely removed by surgery, the administration of drugs inhibiting the insulin release is able to control hypoglycemia in at least 50% of patients.
Non-functioning neuroendocrine tumors of the gastro-entero-pancreatic tract are usually treated by surgery. Surgery is indicated when the dimension of tumors is approximately 2 cm in diameter or when imaging exams during the follow-up show a significant growth of lesions. In case of unresectable tumors or advanced metastatic cancer some medical therapies can be considered such as SSAs, peptide receptor radionuclide therapy (PRRT), cytotoxic chemotherapy, inhibitors of thyrosin kinase receptors and inhibitors of mammalian target of rapamycin.
Carcinoid tumors are generally removed surgically. Medications including octreotide and lanreotide can be used to treat excess hormone production from these tumors, but the risk for malignant transformation remains. For this purpose, the prophylactic removal of thymus, through a transcervical approach, is recommended at the time of neck surgery for parathyroidectomy.
Lipomas may be removed surgically.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about multiple endocrine neoplasia type 1:
Maria Luisa Brandi, MD, PhD
Fondazione F.I.R.M.O. Onlus
Via San Gallo
50129 Florence, Italy
Phone +39 0552336663
Mobile Phone: +39 337685511
Email: [email protected]
[email protected]
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
TEXTBOOKS
Gagel RF, Marx SJ. Multiple Endocrine Neoplasia. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia, PA: Elsevier Saunders; 2003:1717-1762.
Berkow R., ed. The Merck Manual-Home Edition. 2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:972-974.
Rimoin D, Connor JM, Pyeritz RP, Korf BR. Eds. Emory and Rimoinโs Principles and Practice of Medical Genetics. 4th ed. New York, NY: Churchill Livingstone; 2002:2209-2213.
JOURNAL ARTICLES
Vannucci L, Marini F, Giusti F, Ciuffi S, Tonelli F, Brandi ML. MEN1 in children and adolescents: Data from patients of a regional referral center for hereditary endocrine tumors. Endocrine. 2018 Feb;59(2):438-448. doi: 10.1007/s12020-017-1322-5.
Marini F, Giusti F, Tonelli F, Brandi ML. Management impact: effects on quality of life and prognosis in MEN1. Endocr Relat Cancer. 2017 Oct;24(10):T227-T242. doi: 10.1530/ERC-17-0203.
Giusti F, Cianferotti L, Gronchi G, Cioppi F, Masi L, Faggiano A, Colao A, Ferolla P, Brandi Ml. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1). ENDOCRINE. 2016;vol. 52; p. 495-506, ISSN: 1559-0100, doi: 10.1007/s12020-015-0696-5.
Luzi E, Marini F, Tognarini I, Galli G, Falchetti A, Brandi ML. The Regulatory Network Menin-MicroRNA 26a as a Possible Target for RNA-Based Therapy of Bone Diseases. Nucleid Acid Ther.2012;22:103-8.
Giudici F, Nesi G, Brandi ML, Tonelli F. Surgical management of insulinomas in multiple endocrine neoplasia type 1. Pancreas.2012;41:547-53.
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML. Endocrine Society.Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97: 2990-3011.
Brandi Ml, Tonelli F. Introduction to the 12th International Workshop on Multiple Endocrine Neoplasia. Endocr Pract. 2011;17(suppl 3):1.
Saggini A, Brandi ML. Skin lesions in hereditary endocrine tumor syndromes. Endocr Pract. 2011;17(suppl 3):47-57.
Luzi E, Brandi ML. Are microENAs involved in the endocrine-specific pattern of tumorigenesis in multiple endocrine neoplasia type 1? Endocr Pract. 2011;17(suppl 3):58-63.
Tonelli F, Giudici F, Fratini G, Brandi ML. Pancreatic endocrine tumors in multiple endocrine neoplasia Type 1 syndrome: review of literature. Endocr Pract. 2011;17(suppl 3):33-40.
Brandi ML. Parathyroid gland: Hyperparathyroidism in MEN1 syndrome: time to operate? Nat Rev Endocrinol. 2010;6:604-5.
Luzi E, Marini F, Tognarini I, et al. Rimbozyme-mediated compensatory induction of menin-oncosuppressor function in primary fibroblasts from MEN1 patients. Cancer Gene Ther. 2010;17:814-25.
Falchetti A, Cilotti A, Vaggelli L, et al. A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet. Nat Clin Pract Endocrinol Metab. 2008;4(6):351-7.
Faggiano A, Tavares LB, Tauchmanova L, et al. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients. Clinical Endocrinology.2008;69:756-762.
White ML, Doherty GM. Multiple endocrine neoplasia. Surg Oncol Clin N Am. 2008;17:439-459.
Falchetti A, Marini F, Luzi E, Tonelli F, Brandt ML. Multiple endocrine neoplasms. Best Pract Res Clin Rheumatol.2008;22:149-163.
Busygina V, Bale AE. Multiple endocrine neoplasia type 1 (MEN1) as a cancer predisposition syndrome: clues into the mechanisms of MEN1-related carcinogenesis. Yale J Biol Med.2006;79:105-114.
Marini F, Falchetti A, Del Monte F, et al. Multiple endocrine neoplasia type 1. Orphanet J Rare Dis. 2006;1:38. Published 2006 Oct 2. doi:10.1186/1750-1172-1-38
Pellegata NS, Quintanilla-Martinez L, Siggelkow H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 2006;103:15558-63.
Lambert LA, Shapiro SE, Lee JE, et al. Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Arch Surg. 2005;40:374-382.
Tonelli F, Fratini G, Falchetti A, Nesi G, Brandi ML. Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience. J Intern Med.2005;257:38-49.
Ramage JK, Davies AHG, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours. Gut. 2005;54:1-16.
Kouvaraki MA, Lee JE, Shapiro SE, et al. Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg.2002;137:641-647.
Brandi ML, Gagel RF, Angeli A, et al. Guidelines for the diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab.2001;86:5658-5671.
Norton JA, Alexander HR, Fraker DL, et al. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg. 2001;234:495-505.
Bystrom C, Larsson C, Blomberg C, et al. Localization of the MEN1 gene to a small region with chromosome 11q13 by deletion mapping in tumors. Proc Natl Acad Sci USA.1990;87:1968-1972.
INTERNET
Giusti F, Marini F, Brandi ML. Multiple Endocrine Neoplasia Type 1. 2005 Aug 31 [Updated 2022 Mar 10]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1538/ Accessed Nov 8, 2023.
Diaz-Thomas A. Pediatric Multiple Endocrine Neoplasia. Medscape. Updated: July 15, 2021. https://emedicine.medscape.com/article/923269-overview Accessed Nov 8, 2023.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Multiple Endocrine Neoplasia, Type I; MEN1. Entry No: 131100. Last Edited: 07/21/2023. Available at: https://www.omim.org/entry/131100?search=131100&highlight=131100 Accessed Accessed Nov 8, 2023.
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