Highlights of the 78th Annual Meeting American Thyroid ... - Thyrolink

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6 Thyroid International 2 2008Award LecturesPaul Starr AwardDr Ken Burman, Washington, DC, in his Paul StarrAward Lecture, reviewed recent advances in the investigationof thyroid cancer. Histological variants of papillarythyroid carcinoma differ in prognosis: the tallcell variant has a worse prognosis, while the follicularvariant has a better prognosis. Vascular invasion hasa markedly worse prognosis for distant metastases. Healso reviewed biochemical features of certain cancers.Activated AKT can phosphorylate RAF, inactivatingthe downstream MEK–ERK pathway. Increased AKTactivity has been found in most types of thyroid cancer,but is less common in follicular adenomas. Variousdifferent tyrosine kinases have been reported to displayincreased expression in thyroid cancers: someare overexpressed because they have become fused toother genes, while other cancers display a decrease inthe activities of proteins that inhibit tyrosine kinases.Tumors with foci of cells that have lost cell polarity andintracellular adhesion also show a loss of e-cadherin,which permits β-catenin to enter nuclei and activatea variety of gene pathways. These manifestations ofepithelial-mesenchymal transition are thought to promoteinvasiveness and distant metastases.Van Meter AwardThe Van Meter Award was given to Dr Yuri Nikiforov,Pittsburg, PA, who was recognized for his contributionsto the understanding of radioiodine-induced thyroidcancer. During the Chernobyl nuclear accident, a millionchildren were at risk of exposure to 4 millionCuries of 131 I released into the atmosphere. A dramaticincrease of carcinoma in the thyroid began 4 yearslater. The most salient discovery about the cancers inthese children was that chromosome rearrangements –rather than single base mutations – were the commonestcause of papillary carcinoma following irradiation.The commonest rearrangement (between the RET andhistone H4 genes, both being located on Chromosome10), was found in over 80 % of radiation-induced papillarycarcinoma. The second most common finding wasa BRAF/AKAP9 in-frame fusion on Chromosome 7.About 10 % of the cancers that developed after radiationhave the BRAF/AKAP 9 rearrangement, whereasin sporadic papillary carcinomas, the most commondefect is a single base mutation in the BRAF gene(~ 40 %). Although a wide variety of gene mutationshave been observed in thyroid cancer, the most commonlyencountered appears to involve activation of theMEK–ERK pathway. Nikiforov provided backgroundinformation showing that DNA exists in very largeloops, and each chromosome occupies its own specificregion within the nucleus. When a double-strand breakoccurs in DNA, the complex of proteins that forms toreunite the two strands may also be involved in causingthe chromosome rearrangements. Nikiforov performedrestriction endonuclease digestions on whole cells afterX-radiating them, and deduced that only one doublestrandedDNA preceded the chromosome rearrangementsthat occur either between the RET and H4 geneor between the RET and ELE1 gene.Keynote Clinical AddressAntonio Bianco, Boston, MA, in discussing “The Roleof Thyroid Hormone in the Regulation of Metabolism”reviewed the role of deiodinases (DIOs) in fat metabolism,particularly of DIO2 in brown adipose tissue.The subcellular distribution of DIOs affects the cell’sresponsiveness to T 4 : DIO1 is located on the plasmamembrane, whereas DIO2 is located in the endoplasmicreticulum around the nucleus. Thus, T 3 made by DIO2is more likely to enter the nucleus and to stay longerthan T 3 made at the cell surface by DIO1. Bianco thendescribed the effects of bile acids on the actions ofthyroid hormone on metabolism. Bile acids taken upfrom the gut spill into the systemic circulation andincrease thermeogenesis. TGR5 is a bile acid-bindingprotein found in mature brown fat cells. He noted thatlithocholic and taurocholic acids are the most potent foractivating DIO2 in brown fat. Giving a high-fat diet toTGR5 knock-out mice causes them to gain more weightthan do normal mice. In pre-adipocytes, bile acids notonly can change metabolism but also can cause theirdifferentiation to mature brown fat.
American Thyroid Association – Highlights of the 78 th Annual Meeting7Historical VignetteArthur Schneider, Chicago, IL, presented the Clark T.Sawin Historical Vignette on the subject of “Radiation,Louis Hempelmann and Thyroid Cancer”. In a beautifullydelivered talk, he told the story of the developmentof ionizing radiation leading to the development of thenuclear bomb, as well as early diagnostic and therapeuticuses. Many of these early uses have been implicatedas being involved in the genesis of present day thyroidcancers. He described the seminal studies of Duffy andFitzgerald on the dose–response curve relating radiationto thyroid cancer and in discussing risks from bothexternal and internal radiation stressed the need forlong-term studies extending for 30–40 years or longerbefore such risks can be accurately quantified.retention calculations. Stevan Sherman, Houston, TX,described upcoming therapies for thyroid cancer. Thesewould be principally directed at RAI refractory tumorsand distant metastases and could also be used in treatingmedullary thyroid carcinoma. Therapies currentlyin development are directed at abnormal signaling,cell cycle and apoptosis, and epigenetic modifications,and would include protein kinase inhibitors, VEGFcascade, RET and BRAF, demethylating agents, and histonedeacetylase inhibitors. He stressed that we cannotassume that all tumors handle drugs in the same wayand therefore there was a need to develop individualpersonalized combination therapies.Sidney H. Ingbar Distinguished LectureshipThis year's lecture was delivered by Paul Walfish,Toronto, ON, and lived up to its title “Thyroid HormoneAction: A Second Career Odyssey” by reviewing aremarkable career in many areas of clinical and laboratorythyroidology.Arthur Bauman Clinical Symposiumon Thyroid Cancer ManagementIn this symposium, moderated by Sebastiano Filetti,Rome, Italy, Robert McIntyre, Denver, CO, spoke on thetopic of optimizing initial surgical therapy for thyroidcancer. He contrasted the Japanese practice of prophylacticnode dissection with the more conservativeapproach in the US or Europe. He pointed out the lowlevel of evidence to sustain the approach of central neckdissection with removal of 5–25 nodes. Richard Kloos,Columbus, OH, addressed the topic of optimizing radioiodine(RAI) therapy and reviewed the ATA guidelineson choosing the dose used from a range of 100–300 mCi.He stressed that the minimum dose required should beemployed: low-risk patients should receive 30–100 mCi;medium risk 100–200 mCi, and those with pulmonarymetastases 100–300 mCi. He posed the question “Howwere these numbers arrived at?” He discussed the questionsof quantitative tumor and blood dosimetry, andstressed the possibility of serious complications, particularlyat higher RAI doses. He suggested individualizeddosimetry based on a diagnostic scan coupled with RAI
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