Horm Metab Res 2002; 34(4): 202-206
DOI: 10.1055/s-2002-26712
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Molecular and Biochemical Screening for the Diagnosis and Management of Medullary Thyroid Carcinoma in Multiple Endocrine Neoplasia Type 2A

A.  E.  F.  Vieira 1 , M.  P.  Mello 2 , L.  L.  K.  Elias 3 , I.  F.  Lau 2 , L.  M.  Z.  Maciel 3 , A.  C.  Moreira 3 , M.  Castro 3
  • 1 Department of Clinical Pathology, University of Campinas, Brazil
  • 2 CBMEG, University of Campinas, Brazil
  • 3 Division of Endocrinology, School of Medicine of Ribeirao Preto-USP, Brazil
Further Information

Publication History

7 August 2001

6 December 2001

Publication Date:
30 April 2002 (online)

Abstract

Patients with multiple endocrine neoplasia (MEN) type 2A are at risk for early medullary thyroid carcinoma (MTC). We performed different screening tests for MTC - a recently reported biochemical screening test using omeprazole-induced calcitonin (CT) stimulation and DNA analysis - in fifteen members of two non-consanguineous Brazilian families with MEN 2A. RET proto-oncogene analysis was carried out by direct DNA sequencing of PCR-amplified products for exons 10 and 11. Family 1 showed a germline mutation (C634Y) in three individuals; a sister and a brother with symptomatic MTC; the former also presented with pheochromocytoma and hyperparathyroidism, and her son was a nine-year-old boy of previously unknown status. Family 2 showed the C634R mutation only in the index case, who presented with cutaneous lichen amyloidosis in addition to MTC, pheochromocytoma and hyperparathyroidism. Neither her parents nor her four brothers showed this genetic abnormality, suggesting a de novo RET proto-oncogene mutation in this patient. The controls and patients presented normal basal gastrin levels and a significant increase after omeprazole. Basal CT levels were elevated in patients with MTC and undetectable in control and asymptomatic family members. No subject showed any increase in CT levels after omeprazole treatment. In conclusion, the two most frequent RET proto-oncogene mutations in MEN 2A are present in Brazilian families. In addition, the specificity of basal and omeprazole-stimulated calcitonin is rather limited, and the efficacy of the omeprazole test still needs to be systematically examined. Therefore, RET proto-oncogene analysis must be the first choice for a screening procedure to identify gene carriers in MEN 2A family members and to permit early prophylactic treatment of MTC.

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M. de Castro

School of Medicine of Ribeirao Preto - USP

Av Bandeirantes 3900 · 14049 - 900 Ribeirao Preto - SP · Brazil

Fax: + 55 (16) 633 00 17

Email: castrom@fmrp.usp.br

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