Causes

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 adrenal tumor is called a pheochromocytoma, and the thyroid tumor is a medullary carcinoma of the thyroid.

The tumors involve multiple parts of the thyroid gland or more than one of the parathyroid and adrenal glands. Tumors in the thyroid, adrenal, or parathyroid glands may occur years apart.

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

There are two subtypes of MEN II -- MEN IIa and IIb. MEN IIb is less common.

Symptoms

The symptoms may vary. However, they are similar to those of:

• Medullary carcinoma of the thyroid
• Pheochromocytoma
• Parathyroid adenoma
• Parathyroid hyperplasia

Exams and Tests

To diagnose this condition, the health care provider looks for a mutation in the RET gene. This can be done with a blood test. Additional tests are done to determine which hormones are being overproduced.

A physical examination may reveal:

• Enlarged lymph nodes in the neck
• Fever
• High blood pressure
• Rapid heart rate
• Thyroid nodules

Imaging tests used to identify tumors may include:

• Abdominal CT scan
• Imaging of the kidneys or ureters
• MIBG scintiscan
• MRI of abdomen
• Radioimmune assay of parathyroid hormone
• Thyroid scan
• Ultrasound of the thyroid

Blood tests are used to evaluate the function of each endocrine gland. The following tests may be performed:

• Calcitonin level
• Blood alkaline phosphatase
• Blood calcium
• Blood phosphorus
• Urine catecholamines
• Urine metanephrine

Other tests or procedures that may be done include:

• Adrenal biopsy
• Electrocardiogram (ECG)
• Thyroid biopsy
• Parathyroid biopsy

Treatment

Surgery is needed to remove pheochromocytoma.

For medullary carcinoma of the thyroid, the thyroid gland and surrounding lymph nodes must be totally removed. Thyroid hormone replacement therapy is given after surgery.

If a child is known to carry the RET gene mutation, surgery to remove the thyroid before it becomes cancerous is considered. This should be discussed with a physician who is very familiar with this condition. It would be done at an early age (before age 5) in people with known MEN IIa, and before age 6 months in people with MEN IIb.

Outlook (Prognosis)

Pheochromocytoma is usually not cancerous (benign). Medullary carcinoma of the thyroid is a very aggressive and potentially fatal cancer. However, early diagnosis and surgery can often lead to a cure.

Possible Complications

The spread of cancerous cells is a possible complication.

When to Contact a Medical Professional

Call your health care provider if you notice symptoms of MEN II or if someone in your family receives such a diagnosis.

Prevention

Screening close relatives of people with MEN II may lead to early detection of the syndrome and related cancers.

Alternative Names

Sipple syndrome; MEN II

References

Kronenberg HM. Polyglandular disorders. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 250.

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Neuroendocrine Tumors. National Comprehensive Cancer Network; 2009. Version 2.2009.

Update Date: 3/2/2012

Reviewed by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.