Therapeutic Effectiveness of Screening for Multiple Endocrine Neoplasia Type 2A.

Abstract

Although technological progress revolutionized detection of genetic predisposition to medullary thyroid cancer (MTC), carriers of mutations of disparate risks may not have benefitted alike from screening. This investigation aimed at assessing the achievements of screening for multiple endocrine neoplasia type 2A (MEN 2A) in Germany and identifying current challenges. This was a retrospective analysis comprising 455 carriers at risk of MEN 2A screened and operated between 1963 and 2014. The setting was tertiary surgical referral centers. Included were 175 carriers of American Thyroid Association (ATA) level C mutations (codon 634); 116 carriers of ATA level B mutations (codons 609, 611, 618, 620 and 630); and 164 carriers of ATA level A mutations (codons 768, 790, 791, 804 and 891). The intervention was thyroidectomy. Main outcome measures were percentage of index patients among all carriers and percentage of MTC, node-positive MTC, and biochemical cure among non-index patients. The percentage of index patients among all carriers fell from 50% (ATA level C) and 100% (ATA levels B and A) to 16, 29, and 31%, respectively. Among non-index patients, the percentage of MTC fell for ATA levels C and B but not for ATA level A mutations. The corresponding percentage of node-positive MTC declined since 1963 from 100 to 0% (ATA level C) and since 1995 from 67 to 33% (ATA level B) and from 11 to 10% (ATA level A), whereas biochemical cure increased from 0 to 100% since 1963 (ATA level C), and since 1995 from 71 to 78% (ATA level B) and from 95 to 100% (ATA level A). Screening efforts need to focus on sporadic-appearing MTC to deplete the pool of unrecognized carriers of ATA level B and A mutations and enable earlier pre-emptive thyroidectomy in their offspring.