Thyroid Cancer: Medullary Cancer

Thyroid Cancer: Medullary Cancer
The Third Most Common Thyroid Cancer

            
Medullary tumors are the third most common of all thyroid cancers (about 5 to 8 percent). Unlike papillary and follicular thyroid cancers which arise from thyroid hormone producing cells, medullary cancer of the thyroid originates from the parafollicular cells (also called C cells) of the thyroid. These C cells make a different hormone called calcitonin (thus their name) which has nothing to do with the control of metabolism the way thyroid hormone does. As you will see below, the production of this hormone can be measured after an operation to determine if the cancer is still present, and if it is growing. This cancer has a much lower cure rate than does the "well differentiated" thyroid cancers (papillary and follicular), but cure rates are higher than they are for anaplastic thyroid cancer. Overall 10 year survival rates are 90% when all the disease is confined to the thyroid gland, 70% with spread to cervical lymph nodes, and 20 when spread to distant sites is present.
Characteristics of Medullary Thyroid Cancer

    * Occurs in 4 clinical settings (see below), can be associated with other endocrine tumors
    * Females more common than males (except for inherited cancers)
    * Regional metastases (spread to neck lymph nodes) occurs early in the disease
    * Spread to distant organs (metastasis) occurs late and can be to the liver, bone, brain, and adrenal medulla
    * Not associated with radiation exposure
    * Usually originates in the upper central lobe of the thyroid
    * Poor prognostic factors include age >50, male, distant spread (metastases), and when seen in patients with other endocrine tumors due to MEN II-B syndrome.
    * Residual disease (following surgery) or recurrence can be detected by measuring calcitonin (a hormone that should be measured every 4 months for the first few years and then every 6 months for ever).

Medullary Thyroid Cancer Occurs in Four Clinical Settings

   1. Sporadic- Accounts for 80% of all cases of medullary thyroid cancer. They are typically unilateral and there are no associated endocrinopathies (not associated with disease in other endocrine glands. Peak onset 40 - 60. Females outnumber males by 3:2 ratio. One third will present with intractable diarrhea. Diarrhea is caused by increased gastrointestinal secretion and hypermotility due to the hormones secreted by the tumor (calcitonin, prostaglandins, serotonin, or VIP).
   2. MEN II-A (Sipple Syndrome). Multiple Endocrine Neoplasia Syndromes (abbreviated as "MEN" and pronounced "M", "E", "N") are a group of endocrine disorders which occur together in the same patient and typically are found in families because they are inherited. "Syndromes" are medical conditions which occur in groups of three. Sipple syndrome has [1] bilateral medullary carcinoma or C cell C cel hyperplasia, [2] pheochromocytomand [3] hyperparathyroidism. This syndrome is inherited and is due to a defect of a gene (DNA) which helps control the normal growth of endocrine tissues. This inherited syndrome is passed on to all children who get the gene (inherited in an autosomal dominant fashion), which theoretically, would be 50% of all offspring of a person with this defective gene. Because of this, males and females are equally affected. Peak incidence of medullary carcinoma in these patients is in the 30's.
   3. MEN II-B. This syndrome also has [1] medullary carcinoma and [2] pheochromocytoma, but only rarely will have hyperparathyroidism. Instead these patients have [3] an unusual appearance which is characterized by mucosal ganglioneuromas (tumors in the mouth) and a Marfanoid habitus. Inheritance is autosomal dominant as in MEN II-a, or it can occur sporadically (without being inherited). MEN II-B patients usually get medullary carcinoma in their 30's, and males and females are equally effected. As with MEN II-A, pheochromocytomas must be detected prior to any operation. The idea here is to remove the pheochromocytoma first to remove the risk of severe hypertensive episodes while the thyroid or parathyroid is being operated on.
   4. Inherited medullary carcinoma without associated endocrinopathies. This form of medullary carcinoma is the least aggressive. Like other types of thyroid cancers, the peak incidence is between the ages of 40 and 50.

Management of Medullary Thyroid Cancer

Thyroid gland has 2 lobes connected by an isthmus.In contrast to papillary and follicular cancers, little controversy exits when discussing the management of medullary thyroid cancer. After assessment and treatment of associated endocrine conditions (such as pheochromocytomas if present) by an endocrinologist, all patients should receive total thyroidectomy, a complete central neck dissection (removal of all lymph nodes and fatty tissues in the central area of the neck), and removal of all lymph nodes and surrounding fatty tissues within the side of the neck which harbored the tumor

The Use of Radioactive Iodine Post-Operatively

Although thyroid cells have the cellular mechanism to absorb iodine (see papillary cancer page), medullary thyroid cancer does not arise from this type of thyroid cell. Therefore, radioactive iodine therapy is not useful for the treatment of medullary thyroid cancer. Similarly, if medullary cancer spreads to distant sites, it cannot be found by iodine scanning the way that distant spread from papillary or follicular cancer can.
What Kind of Long-Term Follow Up is Necessary?

In addition to the usual cancer follow up, patients should receive a yearly chest x-ray as well as calcitonin levels Serum calcitonin is very useful in follow up of medullary thyroid cancer because no other cells of the body make this hormone. A high serum calcitonin level that had previously been low following total thyroidectomy is indicative of recurrence. Under the best circumstances, surgery will remove all of the thyroid and all lymph nodes in the neck which harbor metastatic spread. In this case, post operative calcitonin levels will go to zero. This is often not the case, and calcitonin levels remain elevated, but less than pre-operatively. These levels should still be checked every 6 months, and when they begin to rise, a more diligent examination is in order to find the source.