Multiple endocrine neoplasia type 1 overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer's syndrome is part of a group of disorders that affect the endocrine system through development of neoplastic lesions in the pituitary, the parathyroid gland and the pancreas. Multiple endocrine neoplasia type 1 was first described by Dr.Erdheim, a German physician, in 1903 by reporting a case of an acromegalic patient with pituitary adenoma and three enlarged parathyroid glands. Development of multiple endocrine neoplasia type 1 is the result of multiple genetic mutations of mainly MEN1 gene. The pathophysiology of multiple endocrine neoplasia type 1 depends on the histological subtype. Common risk factors in the development of multiple endocrine neoplasia type 1 are family history, history of Zollinger-Ellison syndrome and pituitary dysfunction. Symptoms of multiple endocrine neoplasia type 1 include lethargy, depression, oligomenorrhea, constipation, headache and diarrhea. Biochemical tests and imaging techniques are used to screen for multiple endocrine neoplasia type 1. Symptoms of multiple endocrine neoplasia type 1 include lethargy, depression, oligomenorrhea, constipation, headache and diarrhea. MRI may be helpful in the diagnosis of multiple endocrine neoplasia type 1. Surgery is the mainstay of treatment for multiple endocrine neoplasia type 1.
Historical Perspective
Multiple endocrine neoplasia type 1 was first described by Dr.Erdheim, a German physician, in 1903 by reporting a case of an acromegalic patient with pituitary adenoma and three enlarged parathyroid glands.
Pathophysiology
Development of multiple endocrine neoplasia type 1 is the result of multiple genetic mutations. Gene involved in the pathogenesis of multiple endocrine neoplasia type 1 is MEN1 gene. The pathophysiology of multiple endocrine neoplasia type 1 depends on the histological subtype.
Causes
Multiple endocrine neoplasia type-1 occurs due to the mutations in gene MEN-1. This gene encodes for menin protein. Menin prevents the cells from growing and dividing aggressively. Menin is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. Inactivating mutations of both the copies of the MEN1 gene leads to lack of availability of menin to control cell growth and division. This leads to the formation of tumors characteristic of the MEN-1 syndrome. Why these tumors preferentially affect endocrine tissues is unclear.
Differentiating Multiple endocrine neoplasia type 1 from Other Diseases
Multiple endocrine neoplasia type 1 must be differentiated from other hereditary diseases such as von Hippel-Lindau syndrome, tuberous sclerosis, carney complex, neurofibromatosis type 1, Li-Fraumeni syndrome, multiple endocrine neoplasia type 2, familial hyperparathyroidism, pheochromocytoma and acromegaly.
Epidemiology and Demographics
The prevalence of multiple endocrine neoplasia type 1 is approximately 2-3 per 100,000 individuals worldwide. Patients of all age groups may develop multiple endocrine neoplasia type 1, but it is commonly diagnosed among patients between 18-50 years of age. Multiple endocrine neoplasia type 1 affects men and women equally. There is no racial predilection to multiple endocrine neoplasia type 1.
Risk Factors
Common risk factors in the development of multiple endocrine neoplasia type 1 are family history, history of Zollinger-Ellison syndrome and pituitary dysfunction.
Screening
According to the National Caner Institute, screening for multiple endocrine neoplasia type 1 by imaging studies such as brain MRI, abdominal CT and abdominal MRI is recommended every 3-5 year among patients with pituitary tumors and pancreatic neuroendocrine tumors respectively. Biochemical tests such as serum prolactin, insulin-like growth factor 1, fasting total serum calcium, ionized calcium, parathyroid hormone, fasting serum gastrin, chromogranin A, pancreatic polypeptide, glucagon and vasointestinal polypeptide are recommended every year among patients with pituitary tumors, pancreatic neuroendocrine tumors and primary hyperparathyroidism.
Natural history, Complications and Prognosis
The natural history largely depends on the manifestation and virulence of the manifestations. The manifestations of multiple endocrine neoplasia type 1 usually develop in the first, second, or third decade of life. If left untreated, manifestations of multiple endocrine neoplasia type 1 may gradually worsen, and patients may die of complications of the disease. Life-threatening complications of multiple endocrine neoplasia type 1 include gastrointestinal bleeding, convulsions, hypokalemia, hypoglycemia, and venous thrombosis. Although many tumors associated with multiple endocrine neoplasia type 1 are benign, approximately half of people with multiple endocrine neoplasia type 1 eventually develop a cancerous tumor. The prognosis of multiple endocrine neoplasia type 1 is generally good with treatment. Development of pancreatic cancer is associated with poor prognosis.
Diagnosis
Diagnosis Criteria
There are no established criteria for the diagnosis of MEN 1.
History and Symptoms
Symptoms of multiple endocrine neoplasia type 1 include lethargy, depression, oligomenorrhea, constipation, headache and diarrhea.
Physical Examination
Common physical examination findings of multiple endocrine neoplasia type 1 include rash, lymphadenopathy, fever and abdominal mass.
Laboratory Findings
Laboratory findings consistent with the diagnosis of multiple endocrine neoplasia type 1 include increased parathyroid hormone, increased gastrin, and increased cortisol.
Ultrasound
Abdominal ultrasound may be helpful in monitoring tumor growth and metastases in multiple endocrine neoplasia type 1.
CT
Abdominal CT scan may be helpful in the diagnosis of multiple endocrine neoplasia type 1. Findings on CT scan suggestive of multiple endocrine neoplasia type 1 include thickened stomach rugal folds, multiple gastric nodules and calcified or cystic pancreatic tumors.
MRI
MRI may be helpful in the diagnosis of multiple endocrine neoplasia type 1. Findings on MRI suggestive of multiple endocrine neoplasia type 1 include diffuse heterogenous enhancement of T1 C+ (Gd), low T1 signal and high T2 signal.
Other Imaging Findings
Other imaging studies for multiple endocrine neoplasia type 1 include fluoro-di-glucose-PET/CT, venous sampling, angiography and endovascular procedures, such as trans-arterial chemo-embolization (TACE).
Other Diagnostic Studies
Other diagnostic studies for multiple endocrine neoplasia type 1 include genetic testing, which demonstrates gene mutation in proband of MEN1 gene.
Treatment
Medical Therapy
Pharmacologic medical therapies for multiple endocrine neoplasia type 1 include cabergoline, somatostatin analogues, and H2-receptor blockers.
Surgery
Surgery is the mainstay of treatment for multiple endocrine neoplasia type 1.
Primary Prevention
There is no established method for prevention of Multiple endocrine neoplasia 1.
Secondary Prevention
According to the National Cancer Institute, surveillance for multiple endocrine neoplasia type 1 by imaging studies such as brain MRI, abdominal CT and abdominal MRI is recommended every 3-5 year among patients with pituitary tumors and pancreatic neuroendocrine tumors respectively. Biochemical tests such as serum prolactin, insulin-like growth factor 1, fasting total serum calcium, ionized calcium, parathyroid hormone, fasting serum gastrin, chromogranin A, pancreatic polypeptide, glucagon and vasointestinal polypeptide are recommended every year among patients with pituitary tumors, pancreatic neuroendocrine tumors and primary hyperparathyroidism.
Future or Investigational therapies
Future or investigational therapies of multiple endocrine neoplasia type 1 include TRK-inhibitors (tropomyosin receptor kinase inhibitors), mTOR inhibitors, thienopyrimidine analogs and molecular phenotyping.