Table 6. American Thyroid Association Management Guidelines for MEN2A/FMTC and MEN2Ba continued...
All patients who have undergone parathyroid surgery with autotransplantation of parathyroid tissue should be monitored for hypoparathyroidism.[25,226,227]
Medical therapy of hyperparathyroidism has gained popularity with the advent of calcimimetics, agents that sensitize the calcium-sensing receptors on the parathyroid glands to circulating calcium levels and thereby reduce circulating PTH levels. In a randomized, double-blind, placebo-controlled trial, cinacalcet hydrochloride was shown to induce sustained reduction in circulating calcium and PTH levels in patients with primary hyperparathyroidism. In patients who are high-risk surgical candidates, those with recurrent hyperparathyroidism, or those in whom life expectancy is limited, medical therapy may be a viable alternative to a surgical approach.
Level of evidence: 5
Mode of inheritance
All of the MEN2 subtypes are inherited in an autosomal dominant manner. For the child of someone with MEN2, the risk of inheriting the MEN2 mutation is 50%. Some individuals with MEN2, however, carry a de novo gene mutation; that is, they carry a new mutation that was not present in previous generations of their family and thus do not have an affected parent. The proportion of individuals with MEN2 who have an affected parent varies by subtype.
MEN2A: About 95% of affected individuals have an affected parent. It is appropriate to evaluate the parents of an individual with MEN2A for manifestations of the disorder. In the 5% of cases that are not familial, either de novo gene mutations or incomplete penetrance of the mutant allele is possible.
FMTC: Multiple family members are affected; therefore, all affected individuals inherited the mutant gene from a parent.
MEN2B: About 50% of affected individuals have de novo RET gene mutations, and 50% have inherited the mutation from a parent.[230,231] The majority of de novo mutations are paternal in origin, but cases of maternal origin have been reported.
Siblings of a proband: The risk to siblings depends on the genetic status of the parent, which can be clarified by pedigree analysis and/or DNA-based testing. In situations of apparent de novo gene mutations, germline mosaicism in an apparently unaffected parent must be considered, even though such an occurrence has not yet been reported.
The psychosocial impact of genetic testing for mutations in RET has not been extensively studied. Published studies have had limitations such as small sample size and heterogeneous populations; thus, the clinical relevance of these findings should be interpreted with caution. Identification as the carrier of a deleterious mutation may affect self-esteem, family relationships, and quality of life. In addition, misconceptions about genetic disease may result in familial blame and guilt.[234,235] Several review articles outline both the medical and psychological issues, especially those related to the testing of children.[236,237,238,239] The medical value of early screening and risk-reducing treatment are contrasted with the loss of decision-making autonomy for the individual. Lack of agreement between parents about the value and timing of genetic testing and surgery may spur the development of emotional problems within the family.