Skip to content
My WebMD Sign In, Sign Up

Cancer Health Center

Font Size

Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®): Genetics - Health Professional Information [NCI] - Multiple Endocrine Neoplasia Type 2

Clinical Description

The endocrine disorders observed in multiple endocrine neoplasia type 2 (MEN2) are medullary thyroid cancer (MTC); its precursor, C-cell hyperplasia (CCH); pheochromocytoma; and parathyroid adenomas and/or hyperplasia. MEN2-associated MTC is often bilateral and/or multifocal and arises in the background of CCH. In contrast, sporadic MTC is typically unilateral and/or unifocal. Since approximately 75% to 80% of sporadic cases also have associated CCH, this histopathologic feature cannot be used as a predictor of familial disease.[1] Metastatic spread of MTC to regional lymph nodes (i.e., parathyroid, paratracheal, jugular chain, and upper mediastinum) or to distant sites, such as the liver, is common in patients who present with a palpable thyroid mass or diarrhea.[2,3] Although pheochromocytomas rarely metastasize, they can be clinically significant in cases of intractable hypertension or anesthesia-induced hypertensive crises. Parathyroid abnormalities in MEN2 can range from benign parathyroid adenomas or multigland hyperplasia to clinically evident hyperparathyroidism with hypercalcemia and renal stones.

Historically, individuals and families with MEN2 were classified into one of the following three clinical subtypes based on the presence or absence of certain endocrine tumors in the individual or family:

  1. MEN2A (OMIM).
  2. Familial medullary thyroid carcinoma (FMTC) (OMIM).
  3. MEN2B (OMIM).

Current stratification is moving away from a solely phenotype-based classification and more toward one that is based on genotype (i.e., the mutation) and phenotype.[4]

Clinical findings in the three MEN2 subtypes are summarized in Table 3. All three subtypes confer a high risk of MTC; MEN2A and MEN2B confer an increased risk of pheochromocytoma, and MEN2A has an increased risk of parathyroid hyperplasia and/or adenoma. Classifying a patient or family by MEN2 subtype is useful in determining prognosis and management.

Table 3. Percentage of Patients with Clinical Features of MEN2 by Subtype

SubtypeMedullary Thyroid Carcinoma (%)aPheochromocytoma (%)aParathyroid Disease (%)a
FMTC = familial medullary thyroid carcinoma; MEN2 = multiple endocrine neoplasia type 2.
a Percentages based on observations in referral populations.[5,6,7,8,9]
MEN2A955015–30
FMTC~10000
MEN2B10050Uncommon

MTC and C-Cell Hyperplasia

MTC originates in calcitonin-producing cells (C-cells) of the thyroid gland. MTC is diagnosed when nests of C-cells extend beyond the basement membrane and infiltrate and destroy thyroid follicles. CCH is diagnosed histologically by the presence of an increased number of diffusely scattered or clustered C-cells.[10,11] Individuals with RET (REarranged during Transfection) mutations and CCH are at substantially increased risk of progressing to MTC, although such progression is not universal.[12,13] MTC and CCH are suspected in the presence of an elevated plasma calcitonin concentration.

A study of 10,864 patients with nodular thyroid disease found 44 (1 of every 250) cases of MTC after stimulation with calcitonin, none of which were clinically suspected. Consequently, half of these patients had no evidence of MTC on fine-needle biopsy and thus might not have undergone surgery without the positive calcitonin stimulation test.[14] CCH associated with a positive calcitonin stimulation test occurs in about 5% of the general population; therefore, the plasma calcitonin responses to stimulation do not always distinguish CCH from small MTC and cannot always distinguish between carriers and noncarriers in an MEN2 family.[12,13,15]

1|2|3|4|5|6|7|8|9|10|11|12|13|14|15|16|17|18|19

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
Next Article:

Today on WebMD

Building a Support System
Blog
cancer fighting foods
SLIDESHOW
 
precancerous lesions slideshow
SLIDESHOW
quit smoking tips
SLIDESHOW
 
Jennifer Goodman Linn self-portrait
Blog
what is your cancer risk
HEALTH CHECK
 
colorectal cancer treatment advances
Video
breast cancer overview slideshow
SLIDESHOW
 
prostate cancer overview
SLIDESHOW
lung cancer overview slideshow
SLIDESHOW
 
ovarian cancer overview slideshow
SLIDESHOW
Actor Michael Douglas
Article