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      Area under the curve of TSH after levothyroxine withdrawal versus administration of recombinant human TSH (rhTSH): possible implications for tumor growth Translated title: Área sob a curva de TSH após suspensão da levotiroxina versus administração do TSH recombinante humano: possíveis implicações no crescimento tumoral

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          Abstract

          OBJECTIVE: The levothyroxine withdrawal (L-T4) for some weeks results in prolonged exposure to elevated TSH. In contrast, administration of recombinant human TSH (rhTSH) promotes a short period of hyperthyrotropinemia. The objective of this study was to compare the area under the curve (AUC) of TSH obtained after L-T4 withdrawal versus administration of rhTSH. METHODS: Thirty patients received 0.9 mg rhTSH for two consecutive days, and 64 were prepared by L-T4 withdrawal for four weeks, with the latter being reintroduced 48 hour after 131I. Measurement of TSH were performed before the first rhTSH ampoule; immediately before and seven and 14 days after 131I; before L-T4 withdrawal; and, weekly, up to two months after 131I. RESULTS: The AUC obtained after rhTSH was 4.6 times smaller than that obtained after L-T4 withdrawal (532 versus 2,423 mIU/L per day). It should be emphasized that, on average, in the latter group, 58.5% of the AUC corresponded to the period after reintroduction of hormone therapy. CONCLUSIONS: Surprising difference in the TSH AUC was demonstrated between rhTSH administration versus L-T4 withdrawal.

          Translated abstract

          OBJETIVO: A suspensão de levotiroxina (L-T4) por algumas semanas resulta em exposição prolongada ao TSH elevado. Em contraste, a administração do TSH recombinante (rhTSH) promove um curto período de hipertirotropinemia. O objetivo deste estudo foi comparar a área sob a curva (do inglês "area under the curve", AUC) do TSH obtida após suspensão da L-T4 versus a administração do rhTSH. MÉTODOS: Trinta pacientes receberam 0,9 mg de rhTSH por dois dias consecutivos, e 64 foram preparados com suspensão da L-T4 por quatro semanas, com reintrodução dessa terapia 48 horas após o radioiodo. As medidas de TSH foram realizadas antes da primeira ampola de rhTSH; imediatamente antes e sete e 14 dias após o 131I; antes da suspensão da L-T4; e, semanalmente, até dois meses após o 131I. RESULTADOS: A AUC do TSH obtida após rhTSH foi 4,6 vezes menor do que a alcançada após suspensão da L-T4 (532 versus 2.423 mUI/L ao dia). Enfatiza-se que, em média, no último grupo, 58,5% da AUC correspondeu ao período após a reintrodução da terapia hormonal. CONCLUSÕES: Surpreendente diferença na AUC do TSH foi demonstrada entre a administração do rhTSH versus suspensão da L-T4.

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          Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis.

          Reliable prognostic factors are needed in papillary thyroid cancer patients to adapt initial therapy and follow-up schemes to the risks of persistent and recurrent disease. OBJECTIVE AND SETTINGS: To evaluate the respective prognostic impact of the extent of lymph node (LN) involvement and tumor extension beyond the thyroid capsule, we studied a group of 148 consecutive papillary thyroid cancer patients with LN metastases and/or extrathyroidal tumor extension. Initial treatment, performed at the Institut Gustave Roussy between 1987 and 1997, included in all patients a total thyroidectomy with central and ipsilateral en bloc neck dissection followed by radioactive iodine ablation. Uptake outside the thyroid bed, demonstrating persistent disease, was found on the postablation total body scan (TBS) in 22% of the patients. With a mean follow-up of 8 yr, eight patients (7%) with a normal postablation TBS experienced a recurrence. Ten-year disease-specific survival rate was 99% (confidence interval, 97-100%). Significant risk factors for persistent disease included the numbers of LN metastases (>10) and LN metastases with extracapsular extension (ECE-LN >3), tumor size (>4 cm), and LN metastases location (central). Significant risk factors for recurrent disease included the numbers of LN metastases (>10), ECE-LN (>3), and thyroglobulin level measured 6-12 months after initial treatment after T4 withdrawal. We highlight an excellent survival rate and suggest risk classifications of persistent and recurrent disease based on the numbers of LN metastases and ECE-LN, LN metastases location, tumor size, and thyroglobulin level.
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            A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.

            Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.
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              Preparation with recombinant human thyroid-stimulating hormone for thyroid remnant ablation with 131I is associated with lowered radiotoxicity.

              Preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation than does hypothyroidism. The objective of this prospective study was to compare the damage caused by 131I (3.7 GBq) when these 2 preparations are used. Ninety-four consecutive patients who underwent total thyroidectomy and remnant ablation with 3.7 GBq of 131I were studied. Thirty patients (group A) received rhTSH, and 64 (group B) were prepared by levothyroxine withdrawal. Damage to salivary glands, ovaries, and testes; hematologic damage; and oxidative injury were evaluated by measurement of serum amylase, follicle-stimulating hormone (FSH), complete blood count, and plasma 8-epi-PGF2alpha before and after radioiodine. The 2 groups were similar in sex, age, and the results of baseline assessment. The rate of successful ablation (stimulated thyroglobulin level < 1 ng/mL and negative findings on neck ultrasonography) was 90% in group A and 80% in group B. Considering only patients with a preablation thyroglobulin level greater than 1 ng/mL, these rates were 80% and 70.6%, respectively. Only 1 patient (3.3%) reported transient headaches with rhTSH. Elevated FSH levels after therapy were observed in 4 of 9 (44%) men in group A versus 16 of 18 (89%) in group B (P < 0.03), with a mean increase of 105% versus 236% (P < 0.001), respectively. In women, elevated FSH was observed in 1 of 13 (7.7%) patients in group A versus 6 of 30 (20%) in group B (P = 0.4), with a mean increase of 65% versus 125% (P < 0.001). Thrombocytopenia or neutropenia occurred in 2 of 28 (7%) patients in group A versus 12 of 56 (21.4%) in group B (P = 0.1), with a mean decrease of 20% versus 45% and 25% versus 52% (P < 0.01) for neutrophils and platelets, respectively. Hyperamylasemia and symptoms of acute sialoadenitis occurred in 11 of 30 (36.6%) versus 48 of 60 (80%) (P < 0.001) and in 9 of 30 (30%) versus 35 of 60 (58.3%) (P = 0.01), respectively. 8-Epi-PGF2alpha was found to be elevated after 131I in 14 of 25 (56%) patients in group A versus 45 of 45 (100%) in group B (P < 0.001), with a mean increase of 60% versus 125% (P < 0.001). The lower radiotoxicity with rhTSH, suggested in dosimetry studies, was confirmed in the present prospective investigation, and this advantage occurred without compromising the efficacy of treatment.
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                Author and article information

                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo, SP, Brazil )
                1677-9487
                August 2009
                : 53
                : 6
                : 767-770
                Affiliations
                [01] Belo Horizonte MG orgnameSanta Casa de Belo Horizonte orgdiv1Departamento de Tireoide Brasil
                Article
                S0004-27302009000600012 S0004-2730(09)05300612
                10.1590/S0004-27302009000600012
                4d7d78df-aebd-46ae-837e-1839fb13c220

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 02 June 2009
                : 25 February 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 17, Pages: 4
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                SciELO Brazil


                Thyroid neoplasms,tumor growth,recombinant human TSH,Neoplasias da glândula tireoide,crescimento tumoral,TSH recombinante humano

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