Acknowledgement of Multiple Endocrine Neoplasia Type 1 has not been added yet.

MEN1 is rare, with an estimated prevalence of approximately 1 in 30,000 individuals worldwide. It affects males and females equally and is seen across all ethnic groups. Most individuals are diagnosed in early to middle adulthood ages 20-40 years, though genetic testing can identify carriers before symptoms appear. If one parent has MEN 1, their child is 50% more likely to also have MEN 1.

Name	Abbreviation
Wermer's syndrome
Multiple Endocrine Adenomatosis Type 1

MEN1 is caused by mutations in the MEN1 gene located on chromosome 11q13 (see RareShare Guide on Chromosomal Nomenclature), which encodes menin, a tumor suppressor protein that helps prevent cells from growing and dividing too quickly. Menin regulates cell growth, DNA repair, and apoptosis (cell burst). Loss-of-function mutations lead to uncontrolled cell proliferation in endocrine tissues. In about 90% of cases, MEN1 is inherited from an affected parent in an autosomal dominant pattern (see RareShare Guide on Genetic Inheritance), while 10% arise from new (de novo) mutations. The disease follows a "two-hit" model, where both copies of the MEN1 gene must be inactivated for tumors to form.

The symptoms of MEN1 depend on which endocrine glands are affected and the hormones secreted:

• Parathyroid tumors (90% of cases): Cause primary hyperparathyroidism (high concentration of parathyroid hormone which causes loss of calcium), leading to hypercalcemia (loss of calcium), fatigue, kidney stones, abdominal pain, constipation, and bone pain.

• Pancreatic neuroendocrine tumors (60–70%): May secrete various hormones:

  • Gastrinomas (too much stomach acid) → Zollinger-Ellison syndrome (peptic ulcers, diarrhea, acid reflux)

  • Insulinomas (too much insulin) → Hypoglycemia (blood glucose level is too low), sweating, confusion, weakness

  • Glucagonomas (too much glucagon that breaks down into glucose) or VIPomas → Skin rash, weight loss, or watery diarrhea

• Pituitary tumors (30–40%): Often prolactinomas (too much prolactin that can affect sex hormones), leading to galactorrhea (milk excretion from breasts), amenorrhea (absence of menstrual periods), infertility, or impotence; less commonly, growth hormone or ACTH-producing tumors cause acromegaly (overgrowth of bone or soft tissue) or Cushing’s disease.

• Other manifestations can include adrenal tumors, carcinoid tumors, and facial angiofibromas (benign tumor in any part of the body) or collagenomas (benign skin lesions).

MEN1 is diagnosed based on clinical, biochemical, and genetic criteria. A diagnosis is confirmed if an individual meets one of the following:

1. Clinical diagnosis: Two or more primary MEN1-related endocrine tumors (parathyroid, pituitary, or pancreatic).

2. Familial diagnosis: One MEN1-related tumor in a person with a first-degree relative who has MEN1.

3. Genetic diagnosis: Detection of a germline MEN1 gene mutation, with or without symptoms.

• Biochemical testing:

  • Elevated serum calcium and parathyroid hormone (PTH) for hyperparathyroidism

  • Increased gastrin, insulin, glucagon, or VIP levels for pancreatic tumors

  • Elevated prolactin or growth hormone for pituitary tumors

• Imaging studies:

  • MRI or CT scans of the pituitary and abdomen to detect tumors

  • Endoscopic ultrasound (EUS) for pancreatic neuroendocrine tumors

  • Nuclear imaging (e.g., Ga-68 DOTATATE PET/CT) for localization of neuroendocrine tumors

  • Genetic testing: Confirms MEN1 mutation in the patient and enables predictive testing in at-risk relatives.

Treatment focuses on managing hormonal excess and removing or controlling tumor growth:

• Parathyroidectomy: Surgical removal of overactive parathyroid glands for hypercalcemia control.

• Medical management:

  • Proton pump inhibitors (PPIs) for gastrinomas

  • Diazoxide for insulinomas

  • Somatostatin analogs (octreotide, lanreotide) to control hormone secretion and tumor growth

• Pituitary tumors: Treated with dopamine agonists (e.g., cabergoline for prolactinomas) or surgery if large or symptomatic.

• Pancreatic tumors: Surgical resection or, for inoperable cases, targeted therapies (everolimus, sunitinib) or chemotherapy.

• Ongoing surveillance: Regular biochemical and imaging screening is essential to detect new tumors early.

MEN1 is a chronic and lifelong condition, but with early detection and careful management, most individuals have a near-normal life expectancy. The prognosis largely depends on the type and behavior of pancreatic neuroendocrine tumors, which can become malignant and metastasize. Regular follow-up and genetic counseling for family members are crucial to prevent complications and improve outcomes. Advances in imaging, surgery, and targeted therapies have significantly improved both survival and quality of life for patients with MEN1.

Tips or Suggestions of Multiple Endocrine Neoplasia Type 1 has not been added yet.

1. Mayo Clinic - MEN 1

2. NIDDK - MEN 1

3. Cleveland Clinic - MEN 1

4. NCBI StatPearls - MEN 1