Abstract
Presymptomatic screening of medullary thyroid carcinoma in MEN IIA families enables the early diagnosis of this tumor with its significant morbidity. Biochemical screening consists of basal and stimulated serum calcitonin evaluation. Genetic screening is based on DNA analysis using linked DNA markers. Thyroidectomy at an occult tumor stage may be curative. Calcitonin measurement was carried out in 58 apparently unaffected family members at risk and 11 MEN IIA patients. Calcitonin elevation was detected in nine individuals. All nine underwent thyroidectomy. Histologic examination confirmed medullary thyroid carcinoma in eight patients and in one case C cell hyperplasia. Postoperatively, eight patients (89%) are clinically and biochemically tumor-free (mean follow-up 30 months). DNA screening results in one affected family are presented. DNA analysis allowed recognition of one apparently unaffected individual at risk as a MEN IIA gene carrier. One family member at risk was found not to carry the gene and may be excluded from further screening.
Résumé
Le dépistage du cancer médullaire de la thyroïde avant l'apparition des symptômes dans les familles MEN 2A facilite le diagnostic de cette maladie accompagnée d'une morbidité non négligeable. Le dépistage biochimique consiste en une évaluation de la calcitonine basale et stimulée. Le dépistage génétique comporte une analyse de l'ADN qui utilise des marqueurs spécifiques des liaisons d'ADN. La thyroïdectomie a des chances d'être curative au stade de tumeur occulte. La calcitonine a pu ètre mesurée chez 58 membres d'une famille atteinte mais sans symptômes et chez 11 patients MEN 2A. La calcitonine était élevée chez 9. Tous ces patients ont eu une thyroïdectomie et un cancer médullaire a été retrouvé chez 8 et une hyperplasie des cellules C chez le neuvième. Postopérativement, 8 patients (89%) sont sans tumeur clinique et biologique (suivi moyen: 30 mois). Les résultats du dépistage par l'ADN chez une famille atteinte sont présentés et a permis d'identifier un seul membre apparemment non symptomatique qui était à risque de porter le gêne MEN 2A. On a déterminé également qu'un membre n'était pas porteur du gêne; il peut être exclu de tout examen de dépistage ultérieur.
Resumen
El tamizaje presintomático del carcinoma medular de la glándula tiroides en familias con síndrome NEM 2A hace posible el diagnóstico precoz de este tumor, el cual en forma característica se asocia con significativa morbilidad. El tamizaje bioquímico consiste en la determinación de los niveles calcitonina sérica basal y estimulada. El tamizaje genético se basa en el análisis de ADN utilizando marcadores ligados al ADN. La tiroidectomía que se realiza cuando el tumor es todavía clínicamente oculto puede ser curativa. La determinación de calcitonina fue realizada en 58 familiares aparentemente no afectados pero de reconocido riesgo y en 11 pacientes con síndrome NEN 2A; se detectó calcitonina elevada en 9 individuos, y todos los nueve fueron sometidos a tiroidectomía. El examen histológico confirmó carcinoma medular en 8 e hiperplasia de células C en 1. Postoperatoriamente 8 pacientes (89%) se hallan clínica y bioquimicamente libres de tumor (promedio del seguimiento, 30 meses). Se presentan los resultados del tamizaje de ADN en una familia afectada. El análisis de ADN permitió el reconocimiento de un individuo aparentemente no afectado pero de riesgo como portador del gen NEM 2A. Un familiar con riesgo fue marcado como no portador del gen y puede ser excluído de tamizajes ulteriores.
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Frilling, A., Röher, HD. & John Ponder, B.A. Presymptomatic screening for medullary thyroid carcinoma in patients with multiple endocrine neoplasia type 2A. World J. Surg. 18, 577–581 (1994). https://doi.org/10.1007/BF00353769
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DOI: https://doi.org/10.1007/BF00353769