Endocrine Abstracts

Context: Clinical studies are needed to classify rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC) into one of three clinical risk groups.

Objective: We analyzed genotype–phenotype correlations associated with the RET protooncogene mutation R770Q in exon 13 which was detected simultaneously with a Y791N mutation in the same family.

Results: Calcitonin determination in a 43-year-old female patient with multinodular goiter showed elevated levels (757 pg/ml; normal range <11 pg/ml). CEA was also elevated (27.6 ng/ml (<2.5 ng/ml). Ultrasound revealed a 2.2 cm hypoechogenic nodule on the left side. Plasma and urine catecholamines and metanephrines were in the normal range. RET analysis revealed a new mutation in exon 13 R770Q (CGA>CAA) in the patient. Screening of the sister of the index patient revealed surprisingly another, previosly not described amino-acid substitution Y791N (TAT791AAT) in the RET protooncogene. In the parents the R770Q mutation was detected in the mother, the Y791N mutation in the father. In the index case a thyroidectomy with central and lateral node dissection was done. Histology revealed MTC in a mixed variance with follicular cancer of 2 cm diameter, no lymph node involvement in 26 removed lymph nodes (T1N0M0). Postoperatively there is no increase of calcitonin after pentagastrin stimulation, the patient is biochemically cured concerning MTC. In all other gene carriers (aged 44–70 years), calcitonin levels were in the normal range, therefore, thyroidectomy had not yet been performed.

Conclusions: Our clinical findings indicate that the RET R770Q mutation may be associated with late-onset nonaggressive disease. For the Y791N mutation no association with MTC could be detected, although other exchanges at position 791 are known causes for MTC. Recommendations for prophylactic thyroidectomy should be individualized depending on stimulated calcitonin levels.