What is multiple endocrine neoplasia type 1?

Multiple endocrine neoplasia type 1 (MEN1, also called Wermer syndrome) is a genetic disease caused by mutations – or genetic changes – in the MEN1 gene. People suffering from MEN1 have a greatly increased risk of developing tumors of the parathyroid along with primary hyperparathyroidism (PHPT) and tumors of the islet cells of the pancreas and the anterior pituitary (anterior pituitary neuroendocrine tumors, PitNET). All in all, the MEN1 tumor spectrum includes more than 20 hormone-producing non-hormone-producing tumors, different combinations of which may occur.

How is multiple endocrine neoplasia type 1 diagnosed?

Genetic Diagnostics

Genetic testing is advised for the following people:

  • Every person with two or more typical MEN1 tumors (see below)

  • Every person with a typical MEN1 tumor and a first-degree relative with MEN1

  • Every person under 30 years of age with PHPT, precursor lesions of the pancreas, or an islet cell tumor of the pancreas

The diagnosis of “MEN1” is confirmed by the detection of a mutation – or genetic change – in the MEN1 gene.

Clinical Diagnostic Criteria

  • At least two primary, typical MEN1 tumors (e.g. parathyroid tumor, islet cell tumor, or PitNET)

  • One typical MEN1 tumor is enough if one member of the family has been confirmed to have MEN1.

The following are typical MEN1 tumors:

  • Tumors of the parathyroids

  • Tumors of the anterior pituitary (PitNET)

  • Well-differentiated, hormone-producing tumors of the gastrointestinal tract and pancreas (gastrinoma, insulinoma, glucagonoma, VIPoma)

  • Carcinoids (thymic, bronchial, or gastric carcinoids)

  • Tumors of the adrenal cortex

What is the risk of cancer?

Tumors of the parathyroids and PHPT

  • Most frequent MEN1 manifestation, occurring in 95% of patients

  • The first manifestation in 90% of patients, usually occurring between 20 and 25 years of age

  • Characterized by an excessively high level of calcium in the blood

Well-differentiated, hormone-producing tumors of the gastrointestinal tract and pancreas

  • Gastrinomas are tumors that produce the hormone gastrin, leading to increased hydrochloric acid in the stomach, which can cause stomach ulcers to develop. The clinical picture is referred to as Zollinger-Ellison syndrome. Gastrinomas occur in around 40% of patients, and the onset of the disease is usually before 40 years of age. 25% of patients do not have a relative with diagnosed MEN1.

  • Insulinomas are tumors that mainly produce the hormone insulin, which causes sugar to be absorbed by the body’s cells, resulting in low blood sugar level. They occur in around 10% of patients. The age at the onset of the disease with an MEN1 mutation is around 10 years earlier than for insulinomas which do not result from a MEN1 mutation.

  • Glucagonomas are tumors that produce the hormone glucagon, which provides sugar via various metabolic pathways, thereby leading to an elevated blood sugar level.

  • VIPomas are tumors that produce the hormone VIP (vasoactive intestinal polypeptide), which can bring about watery diarrhea and an overly low level of potassium in the blood, among other things.

Tumors of the adenohypophysis (anterior lobe of the hypophysis) = PitNET

  • Occur in 30-55% of patients

  • They are the first manifestation in 10% of familial and 25% of non-familial cases.

  • The most common tumor is a prolactinoma, which produces the hormone prolactin. In women, this can bring about the flow of milk from the breasts, cycle disorders, and sterility. In men, it can lead to impotence, libido disorders, and gynecomastia (growth of the breast glands).

  • GH- and ACTH-producing tumors are less common, and TSH-producing tumors are rare.


  • Thymic, bronchial, and gastric carcinoids occur in around 10% of MEN1 patients and are tumors that arise from cells of the neuroendocrine system.

  • Thymic carcinoids are found more often in men than in women (20:1) and bronchial carcinoids more often in women than in men.

  • Thymic carcinoids together with MEN1 are very aggressive and frequently end in death.

Parathyroid Tumors

  • They occur in 20-40% of MEN1 patients and only rarely produce hormones.

Tumors of the skin

  • Angiofibromas, collagenomas, and lipomas frequently occur as part of MEN1.

What causes multiple endocrine neoplasia type 1?

MEN1 is caused by a genetic change in the MEN1 gene. This gene encodes for the menin protein, which controls the amplification of genetic material during normal metabolism. Now if the MEN1 gene is altered, the protein menin can no longer function correctly, resulting in the development of a tumor.

MEN1 occurs in approx. one in 20.000-40.000 people and is usually passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease. The remaining cases (around 10%) are due to a spontaneous or new mutation, called a de novo mutation.

Is there a treatment?

Treatment recommendations for MEN1 depend on the existing disease:

Tumors of the parathyroids and PHPT

  • Complete or partial removal of the parathyroids (the scope and timing are a still of a controversial nature)

Pituitary Tumors

  • Prolactinoma: dopamine agonists (cabergoline, bromocriptine, pergolide, and quinagolide)

  • GH-producing tumors: operation, somatostatin analogs

  • ACTH-producing tumors: surgical removal of the tumor, radiotherapy

Well-differentiated, endocrine tumors of the gastrointestinal tract and pancreas

  • Gastrinoma: Proton pump inhibitors (PPIs), H2-receptor blockers. A surgical approach is a subject of controversy.

  • Insulinoma: Surgical treatment

  • Gastrinoma: What constitutes the ideal treatment is currently a controversial issue and mainly depends on how much the tumor is spreading and the ability to operate on it.


  • Complete removal if possible; otherwise, long-acting somatostatin analogs, with radiotherapy or chemotherapy if needed

Parathyroid Tumors

  • Surgical treatment with tumors > 4 cm in diameter, striking radiological signs, or significant growth

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Different surveillance examinations are conducted with regard to the various diseases that can occur as part of MEN1:


  • Screening starting at 5 years of age

  • Clinical symptoms: unconsciousness, drowsiness, documented hypoglycemia?

  • Laboratory testing (annual): glucose on an empty stomach and insulin

Neuroendocrine Tumors of Adenohypophysis (PitNET)

  • Screening starting at 5 years of age

  • Clinical symptoms: headaches, visual changes, milk flow, increased growth?

  • Laboratory testing (annual): prolactin, IGF-1

  • Imaging: MRI of the head every 3 years

Parathyroid Adenoma and PHPT

  • Screening starting at 8 years of age

  • Clinical symptoms: back pain, bone pain, feeling of faintness, fatigue, psychological changes, kidney stones, nausea, vomiting, constipation, multiple or pathological fractures?

  • Laboratory testing (annual): calcium

Neuroendocrine tumors of the pancreas

  • Screening starting at 10 years of age

  • Clinical symptoms: usually without symptoms
    VIPoma: excessive diarrhea?
    Glucagonoma: hyperglycemia, nausea, increased urine excretion, thirst?

  • Laboratory testing (annual): possibly chromogranin A, glucagon, proinsulin, pancreatic polypeptide, VIP

  • Imaging: MRI of the abdomen, annually

Adrenocortical Adenomas

  • Screening starting at 10 years of age

  • Imaging: MRI of the abdomen (at the same time as the MRI of the pancreas)

Thymic, bronchial, and gastric carcinoids

  • Screening starting at 20 years of age

  • Clinical symptoms: usually without symptoms; possibly indicated by flush, diarrhea, wheezing, edemas, or abdominal pain

  • Imaging: CT/MRI of the longs and abdomen every 1-2 years


  • Screening starting at 20 years of age

  • Clinical symptoms: abdominal pain, stomach ulcer, taking of proton pump inhibitors?

  • Laboratory testing (annual): gastrin on an empty stomach

Self-Care and Support

What should I pay special attention to?

You should consult a doctor as soon as drowsiness, unconsciousness, a feeling of weakness, fatigue, or even ravenous hunger pangs and increased thirst occur. These may be signs of hyperglycemia or hypoglycemia or other hormonal disruptions. In addition, you should see a doctor if you have complaints of the gastrointestinal tract, such as diarrhea, nausea, vomiting, and abdominal pain. If you develop new anomalies or complaints, such as bone or back pain, headaches, or visual disturbances, they should likewise be evaluated as soon as possible.

Support Groups and Additional Information