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Reports with regard to mutations in the gene of the TSH-R and of the GS-a
subunit that cause thyroid disease are booming. Also in this meeting several
results were communicated. Thus, Wonerow et al., Leipzig, Germany,
reported five new constitutively activating mutations in the TSH-R gene
causing toxic nodules when being somatic or toxic thyroid hyperplasia (non-autoimmune
hyperthyroidism) when being germline mutations.
Derrien et al., Rennes, France, analyzed exon 10 for mutations of the TSH-R gene and exon 8 and 9 for mutations in the GS-a gene in 37 nodules (22 hot and 15 warm or cold) from patients with multinodular goiter. In none of these nodules mutations were found. The authors suggest that mutations in the gene of the TSH-R and the GS-a protein do not play a major role in the etiology of multinodular goiter. Tonacchera et al., Pisa, Italy, looked for mutations in the TSH-R gene in exon 10 in nodules from 4 patients with functionally autonomous multinodular goiter. In each goiter 2 hyperfunctioning nodules coexisted. In two goiters the 2 hyperfunctioning nodules contained different activating mutations in the TSH-R gene and in the 2 other goiters only 1 out of the 2 hyperfunctioning nodules contained a mutation in this gene. In the same goiters no mutations were found in this gene in the cold nodules. (Comment: The previous and this report are contradictory. One of the reasons for this may be the definition of multinodular goiter. Although in the classical definition of multinodular goiter the whole thyroid gland is affected in some way either by nodules, hyperplasia, involution, thyroiditis, or degeneration, some authors define multinodular goiter also for those patients that have several nodules in an otherwise normal thyroid. It is about time that people who find different results come together to sort things out.) Wohlgemuth et al., Leipzig, Germany, investigated small autoradiographically hot areas for TSH-R gene mutations in 8 patients with euthyroid goiter and found in 2 patients mutations that are known to be somatic. Agretti et al., Pisa, Italy, looked for mutations in the gene of the TSH-R in exon 9 en 10 and of the gene of GS-a protein at codons 201 and 227 in 30 consecutive patients with solitary thyroid nodules. Fifteen patients had a toxic adenoma and 15 a cold nodule. All patients were operated and the surgical specimen was further investigated. In 12/15 of patients with toxic adenoma an activating mutation was found in the TSH-R gene and in one (other) patient with a toxic nodule an activating mutation was found in the GS-a gene. No mutations were found in the cold nodules and the authors conclude that the functionally different nodules appear to have a different origin. (Comment: It would be interesting to know if any mutations are present in the gene of the iodide symporter in these cold nodules.) Nygaard et al., Herlev and Odense, Denmark, investigated the long term effects of RAI on thyroid function and size in 62 consecutive patients with a solitary toxic thyroid nodule. Median follow-up was 60 months with a minimum of 12 months. A cure-rate of 75% was seen within 3 months and thyroid volume was reduced by 45% within 2 years. Hypothyroidism developed in 8% of patients with a median follow-up of 36 months. (Comment: Although follow-up with regard to development of hypothyroidism is still short, this low figure reported here, is very satisfying. Although the authors do not stress this point, it is important to deliver RAI when surrounding normal thyroid tissue is still suppressed.) Allory et al., Boulogne-Billancourt, France, tested 68 surgical specimens immunohistologically for proliferation (using MIB-1 antibody) and the presence of thyroglobulin. Twenty-eight specimens were from autonomously functioning thyroid nodules (AFTN), 30 from cold nodules paired for size, and 10 from normal thyroid tissue for control purposes. Expression of proliferation was significantly higher in AFTN than in cold adenomas or normal tissue. No relation was found between proliferation and immunoreactivity for thyroglobulin. (Comment: As AFTN were matched for size with cold nodules, the finding of an increased proliferation in the former is not easily explained.) Leenhardt et al., Paris, France, performed fine needle aspiration biopsy (FNAB), guided by ultrasound, in a series of 516 non-palpable nodules. Diagnostic accuracy of this method was studied on 72/516 cases, in whom 18 thyroid carcinomas were diagnosed at final histology. Diagnosis prior to operation was established in 15/18 carcinomas by FNAB. Thirteen/eighteen presented with a size of 1 cm or greater. The authors conclude that ultrasound guided FAB is indicated when size of the nodule is minimally 1 cm. (Comment: The fact that in 25% (18/72) of "control" cases carcinoma was present, suggests that selection bias torwards malignancy may have been introduced. Furthermore, the important question is, to what extent these tumors are really of biological significance i.e. behave as carcinoma or remain biologically silent. The answer at this moment is not known. At the moment I would discourage physicians to routinely perform ultrasound of the thyroid for the detection of non-palpable thyroid nodules.) |
