Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

BACKGROUND: The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary thyroid carcinoma (MTC). In 4 of 10 families, mutation in exon 10 was found in codon 611. RESULTS: One hundred fifty persons belonging to 30 families were tested, of which 10 families were carriers of RET mutation in exon 10. In 1 of these families with MTC only, 2 brothers were gene carriers of a RET codon 611 mutation and lived without any sign of MTC. One is aged 79 years, and the other died at the age of 71 of other causes. CONCLUSIONS: The results indicate that the gene carrier in families with MTC without other endocrine tumors (FMTC) exhibits a highly variable disease course. A 611 codon mutation is most often a rather mild and slow progression form of MTC. Because 2 gene carriers were still alive at age 70 years without showing any sign of the disease, it is tempting to ask if all gene carriers with a 611 codon mutation without other endocrine tumors should be operated on, and if so, at what age? In the authors' opinion, more information is needed to be able to answer these questions. The current guidelines for treatment of patients with hereditary MTC are discussed.

Oral cancer--results of treatment in the Copenhagen University Hospital.

During the period 1992-96, 304 patients with malignant tumours of the oral cavity were referred to the Department of Head & Neck Oncology, Copenhagen University Hospital. The female:male ratio was 1:2. Age ranged between 20 and 96 years, median 61 years. Ninety-five percent of the tumours were squamous cell carcinomas. Twenty-two percent were in stage I, 21% were in stage II, 21% were in stage III and 36% were in stage IV. Sixty percent of the patients underwent primary surgical resection, combined with reconstructive procedures if necessary. In 39% of all cases, surgery was followed by radiotherapy, while 21% of the patients, mainly stage I and II patients, were only treated surgically. Radiotherapy alone was received by 36% of the patients, mainly stage III and IV. Four percent of the patients received no treatment due to advanced disease or general poor condition. The overall recurrence rate was 42%, ranging from 23% in stage I to 61% in stage IV. Thirty-eight percent of these patients were treated for recurrence, almost exclusively by surgery. The survival rate 1 year after treatment of recurrence was 90%, 60% and 50% for patients in stage I, II and III respectively, while only 1 of 16 patients in stage IV was alive after 1 year. Three-year crude survival for the whole material was 42%, ranging from 58% in stage I to 18% in stage IV. This is an improvement of 12% compared with a similar group of patients treated in our departments in the period 1978-82, when the primary treatment of choice was external irradiation. The survival rate was, as expected, closely related to T- and N-stage at time of diagnosis. In conclusion, we recommend primary surgery followed by irradiation therapy for patients in stages II, III and IV. Surgical treatment of recurrence in patients who were formerly treated by irradiation therapy should be reserved for patients in good general condition and in a low TNM stage, stage IV patients will only benefit from salvage surgery in a few exceptional cases.

Assessment of the influence of thyroglobulin (Tg) autoantibodies and other interfering factors on the use of serum Tg as tumor marker in differentiated thyroid carcinoma.

The purpose of the study was to examine the value of a commercial immunoradiometric (IRMA) method for measuring serum thyroglobulin as a tumor marker after treatment for differentiated thyroid carcinoma. A prospective analysis of consecutive serum samples from 53 patients was performed using the IRMA method and a traditional double antibody radioimmunoassay (RIA). The results were compared with those of 100 healthy control subjects and furthermore the method was validated by investigating sera from 24 patients with Hashimoto's thyroiditis positive for thyroglobulin autoantibodies. Finally, in vitro studies of the influence of thyroglobulin autoantibodies on the method were done. The IRMA method had an acceptable analytical precision and was more sensitive than the RIA. It was furthermore less sensitive to the presence of thyroglobulin autoantibodies but it was affected by them, and it showed less unspecific serum effect. Both methods had limitations as tumor marker when the patients had a thyroid remnant, when serum thyrotropin was not suppressed, and in cases of local recurrence. The highest predictive value was found in patients with distant metastases. Thus, in cases of only slightly elevated serum thyroglobulin, the strongest indication for recurrence is still an increasing serum thyroglobulin level within the same patient rather than a single value.