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Joseph M Shulan, Leonid Vydro, Arthur B Schneider, and Dan V Mihailescu

cancer remain scarce. Several publications have shown that the risk of malignancy in sporadic thyroid nodules increases with serum thyrotropin (TSH) concentrations, even within the normal range ( Boelaert et al . 2006 , Haymart et al . 2008 , Witczak

Open access

Jonathan M Fussey, Robin N Beaumont, Andrew R Wood, Bijay Vaidya, Joel Smith, and Jessica Tyrrell

Biobank Resource under application number 9072. References Boelaert K Horacek J Holder RL Watkinson JC Sheppard MC Franklyn JA 2006 Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated

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E L Mazzaferri and N Massoll

The incidence of differentiated thyroid cancer (DTC) has increased in many places around the world over the past three decades, yet this has been associated with a significant decrease in DTC mortality rates in some countries. While the best 10-year DTC survival rates are about 90%, long-term relapse rates remain high, in the order of 20-40%, depending upon the patient's age and tumor stage at the time of initial treatment. About 80% of patients appear to be rendered disease-free by initial treatment, but the others have persistent tumor, sometimes found decades later. Optimal treatment for tumors that are likely to relapse or cause death is total thyroidectomy and ablation by iodine-131 ((131)I), followed by long-term levothyroxine suppression of thyrotropin (TSH). On the basis of regression modeling of 1510 patients without distant metastases at the time of initial treatment and including surgical and (131)I treatment, the likelihood of death from DTC is increased by several factors, including age >45 years, tumor size >1.0 cm, local tumor invasion or regional lymph-node metastases, follicular histology, and delay of treatment >12 months. Cancer mortality is favorably and independently affected by female sex, total or near-total thyroidectomy, (131)I treatment and levothyroxine suppression of TSH. Treatments with (131)I to ablate thyroid remnants and residual disease are independent prognostic variables favorably influencing distant tumor relapse and cancer death rates. Delay in treatment of persistent disease has a profound impact on outcome. Optimal long-term follow-up using serum thyroglobulin (Tg) measurements and diagnostic whole-body scans (DxWBS) require high concentrations of TSH, which until recently were possible to achieve only by withdrawing levothyroxine treatment, producing symptomatic hypothyroidism. New paradigms, however, provide alternative pathways to prepare patients for (131)I treatment and to optimize follow-up. Patients with undetectable or low Tg concentrations and persistent occult disease can now be identified within the first year after initial treatment by recombinant human (rh)TSH-stimulated serum Tg concentrations greater than 2 microg/l, without performing DxWBS. These new follow-up paradigms promptly identify patients with lung metastases that are not evident on routine imaging, but which respond to (131)I treatment. In addition, rhTSH can be given to prepare patients for (131)I remnant ablation or (131)I treatment for metastases, especially those who are unable to withstand hypothyroidism because of concurrent illness or advanced age, or whose hypothyroid TSH fails to increase.

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José I Botella-Carretero, Manuel Gómez-Bueno, Vivencio Barrios, Carmen Caballero, Rafael García-Robles, José Sancho, and Héctor F Escobar-Morreale

To evaluate cardiovascular functionality in patients with thyroid cancer, we have performed echocardiography and ambulatory blood pressure monitoring in 19 women with differentiated thyroid carcinoma during thyroxine withdrawal, at three time points: the last day on TSH-suppressive thyroxine doses (subclinical or mild hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free triiodothyronine (FT3) levels), and before 131I whole body scanning (overt hypothyroidism). Twenty-one healthy euthyroid women served as controls. When compared with the values at visit 2, when patients had normal serum FT4 and FT3 levels, night-time systolic and mean blood pressure were increased when the patients were mildly hyperthyroid, and night-time systolic, diastolic and mean blood pressure were increased during overt hypothyroidism. The proportion of nondippers (absence of nocturnal decline in blood pressure) was markedly increased compared with healthy controls (7%), when patients were hyper- or hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and FT3 levels (12%). No changes were observed in office blood pressure or in daytime ambulatory blood pressure readings. Diastolic function worsened during thyroxine withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A ratio and the isovolumic relaxation time increased), and cardiac output decreased in parallel with the decrease in heart rate and systolic blood flow. In conclusion, the chronic administration of TSH-suppressive doses of thyroxine and the withdrawal of thyroxine frequently used for the management of differentiated thyroid carcinoma, are associated with undesirable cardiovascular effects.

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Gaëlle Prost, Françoise Bernier-Valentin, Martine Croset, and Bernard Rousset

the size of the thyroid gland in the different groups of mice. Cx32 gene inactivation promotes thyrotropin-stimulated thyroid growth A sodium perchlorate treatment (1% in drinking water) has been administered to WT and Cx32-KO mice (C57Bl/6 strain

Open access

Georgios Kostopoulos, Ioannis Doundoulakis, Christina Antza, Emmanouil Bouras, Krishnarajah Nirantharakumar, Dimitrios Tsiachris, G Neil Thomas, Gregory Y H Lip, and Konstantinos A Toulis

(RAI). According to the European and American Thyroid Association, long-term levothyroxine suppression of thyrotropin (THST) is recommended in high- and selected intermediate-risk patients, whereas a low-normal thyroid-stimulating hormone (TSH) is

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T Kogai, K Taki, and G A Brent

; De Deken et al. 2000 ) produce oxidative conditions by generation of H 2 O 2 , and are required for the normal function of TPO. Since iodide is bound to an organic compound, this process is known as ‘organification’ of iodide. Thyrotropin (TSH

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J L Reverter, S Holgado, N Alonso, I Salinas, M L Granada, and A Sanmartí

for thyroid remnant ablation, and since most differentiated thyroid carcinomas (follicular and papillary) contain functional thyrotropin (TSH) receptors, adjunct therapy with levothyroxine (LT4) to inhibit this stimulating hormone is effective for

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Aparna Lakshmanan, Anna Wojcicka, Marta Kotlarek, Xiaoli Zhang, Krystian Jazdzewski, and Sissy M Jhiang

FBS. PCCl3 cells were maintained in 6H media with 5% bovine serum as described by Liu et al . (2012) . The experiments were performed under acute thyrotropin (TSH) stimulation, where cells were withdrawn from TSH for 5 days (5H media) and then TSH

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M D Ringel and P W Ladenson

Thyroid cancer is a common malignancy with an apparent increasing incidence and a wide spectrum of clinical behavior and therapeutic responsiveness. Recent advances in diagnosis, primary treatment, and long-term monitoring have led to enhanced detection of primary and recurrent disease and improvements in therapy. Controversy still surrounds several issues: the most accurate predictive staging system and histological subclassification scheme, optimal preoperative assessment and surgical extent, appropriate use of radioiodine for remnant ablation, goal for thyrotropin-suppressive thyroid hormone therapy, best practices in immediate postoperative and long-term monitoring, and approach to the patient with thyroglobulin evidence of residual disease. In this paper, recent data related to these controversial issues are critically reviewed.