Multiple Endocrine Neoplasia (MEN) II
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Multiple Endocrine Neoplasia (MEN) II


Multiple endocrine neoplasia II (MEN II) is an uncommon condition passed down through families (inherited) marked by overactivity of the thyroid, adrenal, and parathyroid glands.

Alternative Names

Sipple's syndrome


The cause of MEN II is a defect in a gene called RET. This defect causes many tumors to appear in the same person, but not necessarily at the same time. The type of adrenal tumor is a pheochromocytoma, and the thyroid tumor is a medullary carcinoma of the thyroid.

The disorder may occur at any age, and affects men and women equally. The main risk factor is a family history of MEN II.


  • Severe headache
  • Heart palpitations
  • Rapid heart rate
  • Sweating
  • Chest pain
  • Abdominal pain
  • Nervousness
  • Irritability
  • Loss of weight
  • Diarrhea
  • Cough
  • Cough with blood
  • Fatigue
  • Back pain
  • Increased urine output
  • Increased thirst
  • Loss of appetite
  • Nausea
  • Muscular weakness
  • Depression
  • Personality changes

The symptoms may vary, but are consistent with those of pheochromocytoma, medullary carcinoma of the thyroid, or sometimes hyperparathyroidism.

Exams and Tests

Diagnosis depends on identification of a mutation in the RET gene. This can be done with a blood test.

A physical examination may reveal enlarged cervical (neck) lymph nodes. An examination of the thyroid may reveal one or more thyroid nodules. The patient may have high blood pressure (continual or sporadic), rapid heart rate and fever.

Patients with MEN IIb may have benign tumors (neuromas) of the mucosa, as well as puffy lips and a prominent jaw.

Diagnostic tests are used to evaluate the function of each endocrine gland. The following tests help confirm the diagnosis:

  • Adrenal biopsy showing pheochromocytoma
  • MIBG scintiscan showing tumor
  • MRI of abdomen showing adrenal mass
  • Abdominal CT scan showing mass
  • Elevated urine metanephrine
  • Elevated urine catecholamines
  • Thyroid biopsy showing medullary carcinoma cells
  • Ultrasound of the thyroid revealing a nodule
  • Thyroid scan showing a cold nodule
  • Elevated calcitonin
  • Parathyroid biopsy showing a tumor or hyperplasia
  • Radioimmune assay of parathyroid hormone showing increased levels
  • Increased serum calcium
  • Decreased serum phosphorus
  • Possibly increased serum alkaline phosphatase
  • Imaging of the kidneys or ureters showing calcification or obstruction
  • ECG possibly showing abnormalities


Surgery is needed to remove both the medullary carcinoma of the thyroid and the pheochromocytoma. Medullary carcinoma of the thyroid must be treated with total removal of the thyroid gland and surrounding lymph nodes. Thyroid hormone replacement therapy is given after surgery.

Family members should be screened for the RET gene mutation.

Outlook (Prognosis)

Pheochromocytoma is usually benign (not cancerous), but the accompanying medullary carcinoma of the thyroid is a very aggressive and potentially fatal cancer. The good news is that early diagnosis and surgery can often lead to cure.

Possible Complications

A complication is the metastasis of cancerous cells.

When to Contact a Medical Professional

Call your health care provide if you notice symptoms of MEN II.


Screening of close relatives of a person with MEN II may lead to early detection.

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