Endocrine Abstracts

Mutations in the RET gene are responsible for Multiple Endocrine Neoplasia type 2A (MEN2A), characterised by Medullary Thyroid Carcinoma (MTC) and Pheochromocytoma (PCC). It is well recognised that there is a genotype-phenotype correlation regarding likelihood of endocrine tumour development. The American Thyroid Association (ATA) has published predictive grading to guide clinical management of patients with RET mutations.

Aim: In this study, we aim to assess the prevalence of MTC and PCC in asymptomatic patients, diagnosed with a RET mutation as a result of cascade screening of a proband relation.

Method: Review of electronic records, notes and clinical material collected from patients referred to NET (Neuro Endocrine Tumors) MDM and regional genetics referral centre over last 15 years. The database revealed 30 patients with confirmed MEN 2A, of which 20 were diagnosed after cascade genetic screening. Data from 18 patients was included in the study.

Results: There were 12 males, 6 females with mean age of 32.4±22.5 years (mean±S.D.). 8/18 asymptomatic patients (44.4%) had endocrine tumours diagnosed at or within 12 months of screening (mean age at MEN 2A diagnosis 41.3±16.7 years). 100% (8/8) patients had histologically confirmed MTC, although serum calcitonin was elevated in only in 6/8 (range 16.9–3900 ng/l). 3 of these 8 patients (17%) also had PCC at diagnosis (with elevated catecholamines/ metanephrines), 2 bilateral and 1 unilateral (13×7 cm). In patients with tumour, the most frequent ATA Class was B (7 patients) followed by Class C (1 patient). The most common mutations were of codon C609Y and codon C620R in Exon 10 in 3 patients each, followed by C609R and C634R in 1 each. All 3 patients with synchronous PCC and MTC at presentation had ATA Class B mutations (C620R: 2 patients and C609Y) in Exon 10. In this cohort, mutations were found in Exon 10 in 88% and in Exon 11 in 12%.

Conclusion: Our study revealed the prevalence of previously undiagnosed tumours with cascade screening as 44% for MTC and 17% for PCC. This information is helpful in counselling during cascade screening. These findings emphasise that all patients with MTC should have RET mutation screening.