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MEN II is divided into MEN IIA and MEN II B. It was first described in 1961. It involves abnormalities in the thyroid gland, the adrenal gland and the parathyroid gland. The differentiation between MEN IIA and MEN IIB was identified first in 1975. MEN II A patients do not have mucosal neuromas and do not look like Marfan syndrome patients but MEN IIB patients do. MEN IIA patients are found to have less virulent cancer of the thyroid than MEN IIB patients. MEN IIA patients are much more likely to have parathyroid gland disease than do patients with MEN IIB.
MEN II is familial and caused by mutations in the RET proto-oncogene. It is inherited as an autosomal dominant disease. The rate of penetrance is about 70 percent by the age of 70 years. It causes medullary thyroid cancer, a pheochromocytoma and sometimes a parathyroid adenoma. The frequency of MEN type II is about one in 30,000 to 50,000 individuals. Some patients only get the thyroid medullary cancer and do not get the other findings. Half of those with the abnormal gene will get the disease by age 50 and 70 percent will get the disease by age 70. Some babies can be born with MEN II and can have medullary thyroid cancer at birth.
The diagnosis of MEN II depends on getting a family history of the disease. One can ask about the presence of hyperparathyroidism, thyroid cancer and pheochromocytoma in the history. Diarrhea can be a symptom as can be an elevated prostaglandin or calcitonin levels. There can be high calcium levels, constipation, polyuria, excessive thirstiness, depression, kidney stones, glucose intolerance, GE reflux disease, and fatigue. Bone density may be lost. High blood pressure can be seen in a pheochromocytoma. Chronic constipation can be seen in MEN IIB and skin lesions that itch are often seen in MEN IIA. A thyroid nodule can be seen in medullary thyroid cancer and the appearance of Marfan syndrome characteristics can be seen in MEN II B patients.
In order to diagnose MEN II, the individual should have a genetic screen for the RET mutations to verify the presence of MEN II. Blood levels of calcitonin are looked at as is a urine collection for catecholamines, consistent with pheochromocytoma. A pentagastrin test is done to see if the person has medullary thyroid cancer. CT scan of the adrenal glands can locate a pheochromocytoma as can an MRI examination. CT of the neck can show evidence of thyroid or parathyroid pathology. Radionuclide scanning can determine if there is thyroid metastatic disease. Fine needle aspirate can check for thyroid or parathyroid disease, especially if the blood tests are indicative of disease.
Treatment for MEN II depends on surgical removal of the pheochromocytoma, medullary thyroid cancer or parathyroid adenoma. Patients with MEN IIA disease rarely have a parathyroid adenoma but commonly have a pheochromocytoma. All MEN IIA patients should be screened for pheochromocytoma with consideration to remove the tumor in order to cure it.
Medications given include thyroid hormone replacement at the time the thyroid gland is removed for medullary thyroid cancer. This is given indefinitely to replace lost thyroid hormone due to excision of the thyroid gland. Vitamin D supplements are given in order to allow for maximal calcium absorption. Calcitriol can be given to manage the low calcium levels that occur once the parathyroid glands are removed. Corticosteroids modify the body's immune activity to different things. If the adrenal gland is removed, you need corticosteroid replacement because the ability to make corticosteroids come from the adrenal gland as well as the norepinephrine and epinephrine that are overactive in pheochromocytoma. Mineralocorticoids are replaced for the same reason.
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