Sipple’s syndrome

Alternative names
Multiple Endocrine Neoplasia (MEN) II

Definition

Multiple Endocrine Neoplasia II (MEN II) is a hereditary disorder in which patients develop a type of Thyroid cancer accompanied by recurring cancer of the adrenal glands.

One type of this disease (MEN IIa) is also associated with overgrowth (hyperplasia) of the parathyroid gland.

Causes, incidence, and risk factors

The cause of MEN II is genetic - a mutation in a gene called RET. Multiple tumors may appear in the same person, but not necessarily at the same time. The 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.

Symptoms

     
  • severe headache  
  • 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

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

Signs and tests

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

A physical examination may reveal enlarged cervical Lymph nodes. An examination of the thyroid may reveal a single or multiple thyroid nodules. The patient may have High blood pressure (sustained or episodic), rapid heart rate and elevated temperature.

In MEN IIb, mucosal neuromas (benign tumors of the mucosa) may be present, as well as puffy lips and a prominent jaw.

Diagnostic tests are also used to evaluate the function of each endocrine gland. These 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 nodule  
  • thyroid scan showing cold nodule  
  • elevated calcitonin  
  • parathyroid biopsy showing tumor or hyperplasia  
  • radioimmune assay of parathyroid hormone showing increased level  
  • 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

Treatment

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 removal of surrounding Lymph nodes. Hormone replacement therapy (HRT) is given after surgery.

Family members should be screened for the RET gene mutation.

Expectations (prognosis)
Pheochromocytoma is usually benign (not cancer), but the accompanying medullary carcinoma of the thyroid that characterizes this condition is a very aggressive and potentially fatal cancer. Nonetheless, early diagnosis and surgery can often lead to cure.

Complications
A complication is the metastasis of cancerous cells.

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

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

Johns Hopkins patient information

Last revised: December 3, 2012
by Levon Ter-Markosyan, D.M.D.

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