Multiple Endocrine Neoplasia Type 2
Table 3. Percentage of Patients with Clinical Features of MEN2 by Subtype continued...
Primary Hyperparathyroidism (PHPT)
PHPT is the third most common endocrine disorder in the general population. The incidence increases with age with the vast majority of cases occurring after the sixth decade of life. Approximately 80% of cases are the results of a single adenoma. PHPT can also be seen as a component tumor in several different hereditary syndromes, including the following:
- Hyperparathyroidism-Jaw Tumor syndrome.
- Familial Isolated Hyperparathyroidism.
Hereditary PHPT is typically multiglandular, presents earlier in life, and can have histologic evidence of both adenoma and glandular hyperplasia.
Clinical Diagnosis of MEN2 Subtypes
The diagnosis of the three MEN2 clinical subtypes relies on a combination of clinical findings, family history, and molecular genetic testing of the RET gene (chromosomal region 10q11.2).
MEN2A is diagnosed clinically by the occurrence of two or more specific endocrine tumors (MTC, pheochromocytoma, or parathyroid adenoma and/or hyperplasia) in a single individual or in close relatives.
The MEN2A subtype makes up about 60% to 90% of MEN2 cases. The MEN2A subtype was initially called Sipple syndrome. Since genetic testing for RET mutations has become available, it has become apparent that about 95% of individuals with MEN2A will develop MTC; about 50% will develop pheochromocytoma; and about 15% to 30% will develop hyperparathyroidism.[13,62,63,64]
MTC is generally the first manifestation of MEN2A. In asymptomatic at-risk individuals, stimulation testing may reveal elevated plasma calcitonin levels and the presence of CCH or MTC.[13,63] In families with MEN2A, the biochemical manifestations of MTC generally appear between the ages of 5 and 25 years (mean 15 years). If presymptomatic screening is not performed, MTC typically presents as a neck mass or neck pain at about age 5 to 20 years. More than 50% of such patients have cervical lymph node metastases. Diarrhea, the most frequent systemic symptom, occurs in patients with a plasma calcitonin level of greater than 10 ng/mL and implies a poor prognosis. Up to 30% of patients with MTC present with diarrhea and advanced disease.