Therapeutic Effectiveness of Screening for Multiple Endocrine Neoplasia Type 2A

Abstract

Context: 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.

Objective: This investigation aimed at assessing the achievements of screening for multiple endocrine neoplasia type 2A (MEN 2A) in Germany and identifying current challenges.

Design: This was a retrospective analysis comprising 455 carriers at risk of MEN 2A screened and operated between 1963 and 2014.

Setting: The setting was tertiary surgical referral centers.

Patients: 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).

Interventions: The intervention was thyroidectomy.

Main outcome measures: 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.

Results: 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).

Conclusions: 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.