Toxic thyroid adenoma and toxic multinodular goiter

  • F. Luft
  • Published 2001 in Journal of Molecular Medicine

Abstract

United States, I was vaguely aware of toxic nodular goiter, but the only patients whom I ever saw with the condition were immigrants from Eastern Europe. I was also aware of the term “jodbasedow,” but mainly for the purpose of preparing for examinations, having never actually clinically encountered it. Moreover, I never saw a single case of hyperthyroidism following the administration of iodinated contrast material while I worked in the United States. When I moved to Germany and learned about the Merseburger triad 10 years ago, all that changed dramatically. Graves’ disease (or Basedow’s disease) retired into the background in terms of common thyroid disorders and toxic nodular goiter moved to the forefront. I did not need to go to a hospital to see cases of nodular goiter; one glance at the passengers in any streetcar in Nuremberg, or for that matter even a streetcar in Berlin today, was enough for me to see as many cases of nodular goiter as I could ever want to. In our clinic for cardiovascular diseases, thyroid function tests are a prerequisite for any iodinated contrast roentgenographic study. Moreover, potassium perchlorate is regularly required as a prophylactic measure. I have now actually seen cases of jodbasedow and have undoubtedly been personally responsible for some of them. What brought about this radical change? The report by Trülzsch et al. [1] in this issue of the Journal of Molecular Medicine may provide some answers. These investigators used denaturing gradient gel electrophoresis to detect thyrotropin or thyroid stimulating hormone (TSH) receptor and Gsα mutations in 75 toxic thyroid nodules. TSH receptor mutations were detected in 57% of the adenoma specimens; Gsα mutations played a lesser role. Perhaps somatic mutations in the TSH receptor should be where I direct my search in terms of understanding the development of toxic nodular goiter and its geographic distribution. Tetraiodothyronine (T4) and triiodothyronine (T3) are the principal thyroid hormones (Fig. 1). They are produced by the coupling of monoand diiodotyrosine molecules. Iodinated tyrosines are produced by the incorporation of organic iodine into tyrosine residues within thyroglobulin, a large glycoprotein molecule. The thyroid gland requires iodine to produce T4 and T3. Inorganic iodine is actively concentrated within the thyroid epithelial cells to a level greater than 30-fold that in plasma. This transport step is competitively inhibited by thiocyanate and perchlorate, which accounts for their antithyroid action and, in the case of perchlorate, clinical utility, in order to prevent jodbasedow. The thyroid has a large storage capacity for iodine, about 8000 μg, which is a reserve sufficient for about 100 days. The gland depends on dietary iodine intake to supplant the iodine stores. Two major influences control the function of the thyroid gland, TSH from the anterior pituitary and the intrathyroidal iodine level. Intrathyroidal iodine stores modulate the stimulatory effects of TSH. TSH is a glycoprotein that attaches to the membrane-bound TSH receptor, a typical G protein coupled unit. The TSH receptor has an extracellular region, a seven-segment transmembrane domain, and an intracellular region that functions as an adenylate cyclase stimulating the formation of intracellular cyclic adenosine monophosphate (cAMP). This second messenger stimulates all the steps in iodine metabolism and thyroglobulin production (Fig. 2). TSH secretion is regulated primarily by two influences. The predominant one is the circulating level of thyroid hormone. The intracellular level of T3 in the pituitary appears to be the specific regulator of TSH synthesis. The intracellular T3 level is determined by the circulating T3 level and the amount that is produced by the deiodination of T4. The second influence controlling TSH production is a hypothalamic neurohumor thyrotropin-releasing hormone. This tripeptide modulates TSH synthesis and release by altering the set point for feedback regulation by T3 and by stimulating transcription of TSH mRNA. Somatic mutations of the TSH receptor gene in thyroid nodules are common. In an earlier study by the authors, mutations were found in 15 of the 31 toxic adenomas examined [2]. The mutations were usually in the transmembrane domain of the TSH reToxic thyroid adenoma and toxic multinodular goiter J Mol Med (2001) 78:657–660 © Springer-Verlag 2001 DOI 10.1007/s001090100187

DOI: 10.1007/s001090100187

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Cite this paper

@article{Luft2001ToxicTA, title={Toxic thyroid adenoma and toxic multinodular goiter}, author={F. Luft}, journal={Journal of Molecular Medicine}, year={2001}, volume={78}, pages={657-660} }