Tomoco Watanabe

Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining

CONTEXT The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. OBJECTIVE The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). DESIGN NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. RESULTS When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). CONCLUSION We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.

Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy

PURPOSE The aim of this study was to evaluate the degree of metastatic bone pain palliation and medullar toxicity associated with samarium-153-EDTMP treatment. METHODS Seventy-three patients with metastatic bone pain having previously undergone therapy with samarium-153-EDTMP (1 mCi/kg) were retrospectively evaluated. Routine follow-up included pain evaluation and blood counts for 2 months after treatment. Pain was evaluated using a subjective scale (from 0 to 10) before and for 8 weeks after the treatment. Blood counts were obtained before treatment and once a week for 2 months during follow-up. Dosimetry, based upon the urinary excretion of the isotope, was estimated in 41 individuals, and the resulting radiation absorbed doses were correlated with hematological data. RESULTS Reduction in pain scores of 75% to 100% was obtained in 36 patients (49%), with a decrease of 50% to 75%, 25% to 50%, and 0% to 25% in, respectively, 20 (27%), 10 (14%), and 7 (10%) patients. There was no significant relationship between the pain response and location of the primary tumor (breast or prostate cancer). Mild to moderate myelosuppression was noted in 75.3% of patients, usually with hematological recovery at 8 weeks. The mean bone marrow dose was 347 +/- 65 cGy, and only a weak correlation was found between absorbed dose and myelosuppression (Pearson coefficient = .4). CONCLUSIONS Samarium-153-EDTMP is a valuable method for metastatic bone pain palliation. A mild to moderate and transitory myelosuppression is the main toxicity observed after samarium therapy, showing a weak correlation with dosimetric measures.

Câncer diferenciado da tiróide de baixo risco: revisão do estado atual da literatura e proposta de conduta

The trend of increasing thyroid cancer has been recognized in Brazil as well as all over the world for several decades. The large use of simple and effective diagnostic tools has significantly contributed to this trend. It is estimated that small carcinomas found at surgery for benign thyroid disorders and by ultrasonography will be identified at grater frequency in the further years. Part of these tumors occurs in low-risk patients that may benefit of less aggressive management strategies. However, the characterization of low-risk patient is still confusing and we lack adequate markers to tell apart patients that may present a troublesome progression of the disease. Furthermore, the use of new follow-up methods has recently changed some guidelines. A multidisciplinary team, including basic scientists, endocrinologists, nuclear medicine physicians, thyroid surgeons and endocrine pathologists reviewed the pertinent literature and, based on their experience, propose some management guidelines for Brazilian patients with low-risk thyroid carcinomas.

Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis

OBJECTIVES To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. SUBJECTS AND METHODS Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. RESULTS In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. CONCLUSION Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development.

Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure

The objective of this study were to obtain dosimetric data from a patient with thyroid cancer simultaneously undergoing peritoneal dialysis therapy, so as to determine the appropriate amount of 131I activity to be applied therapeutically. Percentages of radioiodine in the blood and the whole-body were evaluated, and radiation absorbed doses were calculated according to OLINDA/EXM software. Whole-body 131I effective half-time was 45.5 hours, being four times longer than for patients without any renal dysfunction. Bone-marrow absorbed dose was 0.074 mGy/MBq, with ablative procedure maintenance at 3.7 GBq, as the reported absorbed dose was insufficiently restrictive to change the usual amount of radioiodine activity administered for ablation. It was concluded that radioiodine therapeutic-dose adjustment, based on individual patient dosimetry, is an important way of controlling therapy. It also permits the safe and potential delivery of higher doses of radiation to tumors and undesirable tissues, with a minimum of malignant effects on healthy tissues.

Radioiodine therapy of differentiated thyroid cancer: radiologic impact of out-patient treatment with 100 to 150 mCi Iodine-131 activities

PURPOSE To evaluate exposure and dosimetry to family members and environment due to outpatient radioiodine therapy of differentiated thyroid carcinoma. METHODS Twenty patients were treated with 100-150mCi of iodine-131 on an out-patient basis. Family members dosimetry (n = 27) and potential doses inside the house were measured with thermoluminescent dosimeters. Surface contamination and radioactive wastes were also monitored. RESULTS Less than 1.0 mSv doses were found in 26 co-habitants and 2.8 mSv in a single case (inferior to the acceptable value of 5.0 mSv/procedure). Potential doses in the houses were inferior to 0.25 mSv, excluding the patients bedroom (mean value = 0.69 mSv). Surface contamination (mean = 4.2 Bq.cm-2) were below clearance levels. Radioactive wastes generated had a volume of 2.5 liters and a total activity estimated in 90 microCi, with a calculated exposure close to the background radiation levels. CONCLUSIONS No radiological impact was detected after iodine therapy with 100-150 mCi on an out-patient basis followed by experienced professionals.

Concordance Between Whole-Body Scintigraphy 111In-Octreotide and 99mTc-Sestamibi Uptake in the Detection of Four Tumor-Induced Osteomalacia Cases

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which tumors secrete phosphaturic factors such as fibroblast growth factor-23, which increases renal phosphate excretion, causing hypophosphatemia and osteomalacia. These tumors have mesenchymal origin and are usually small and slow growing, and they can be located anywhere in the body. Because the cure for TIO includes its total resection, the challenge of the treatment is to locate it (1). Once TIOs express somatostatin receptor subtypes 2 and 5, In-octreotide (especially if combined with SPECT/CT [single photon emission computed tomography/computed tomography]) and more recently Ga-DOTANOC PET/CT (positron emission tomography/CT) and Ga-DOTATATE PET/CT have been shown to be excellent in their detection (2). Because TIOs are highly vascular, Tc-sestamibi scintigraphy (MIBI) has also been used for this purpose (3–5). We follow four patients (three women and one man; ages 12–46 y) whose clinical picture and laboratorial data suggested hypophosphatemic osteomalacia, which was confirmed by bone histomorphometry. They underwent whole-body scintigraphy In-Octreotide (Octreoscan) and Tcsestamibi to localize the tumor. Both methods revealed that the same body areas of focally increased tracer uptake in different anatomical sites in each patient (right leg, left foot, left leg, and left knee) were visualized in detail with magnetic resonance image (Figure 1). Histopathological findings after the tumor’s resection confirmed the existence of phosphaturic mesenchymal tumor, a mixed connective tissue variant. In these four patients, both methods (whole-body scintigraphy In-octreotide and MIBI) detected TIOs. For this reason, when Octreoscan is not available, we encourage TIO screening by MIBI.

Correlação entre volume tireoidiano determinado pelo método de ultrassonografia versus cintilografia e sua implicação em cálculos dosimétricos na terapia com radioiodo na doença de Graves

INTRODUCAO: A doenca de Graves (DG) e a causa mais comum de hipertireoidismo e, entre as abordagens terapeuticas mais utilizadas para o tratamento do hipertireoidismo por doenca de Graves, encontram-se a cirurgia, o uso de drogas antitireoidianas e a radioiodoterapia. No calculo dosimetrico para determinacao da dose de radioiodo a ser utilizada, e possivel empregar a ultrassonografia e a cintilografia para avaliar o volume tireoidiano. OBJETIVO: O presente estudo visa correlacionar essas metodologias com enfase no volume obtido e nas implicacoes dosimetricas. SUJEITOS E METODOS: Foram incluidos no estudo 103 pacientes com diagnostico de DG encaminhados para radioiodoterapia. Esses foram submetidos a ultrassonografia da tireoide e a cintilografia tireoidiana, com calculo de volume pela cintilografia baseado na formula de Allen. RESULTADOS E CONCLUSOES: Observou-se boa correlacao entre os dois metodos, porem com massa estimada pela cintilografia sistematicamente maior que a estimada pela ultrassonografia, o que pode acarretar em menor estimativa de dose absorvida quando utilizado o metodo cintilografico.

Clinical and Dosimetric Variables Related to Outcome After Treatment of Graves' Disease With 550 and 1110 MBq of 131I: Results of a Prospective Randomized Trial.

&NA; Therapy of Graves’ hyperthyroidism (HTG) with 131I is still mostly performed on an empirical basis. The present study was carried out to evaluate clinical and dosimetric variables associated with outcome in HTG therapy, which could contribute to planning and defining the most appropriate activity to be administered. Methods Patients with HTG were randomly assigned to therapy with 555 MBq (15mci) or 1110 MBq (30 mCi) of 131I. Estimation of thyroid radiation absorbed dose was made according to MIRD methodology. Success was defined as clinical/laboratory euthyroidism or hypothyroidism one year after therapy. The association between clinical, laboratory, and dosimetric variables with 1-year outcome was measured using bivariate analysis, followed by logistic regression. Results Ninety-one patients included completed the follow-up. Therapeutic success was observed in 77 (84.6%) of them, in a greater proportion when 1110 MBq of 131I was administered as compared with 550 MBq (94.8% vs 77.4%, P = 0.02). Besides administered activity, multivariate analysis indicated that outcome was related to patient age and gland mass. A higher therapeutic success rate was achieved with doses greater than 300 Gy as compared with doses less than 300 Gy (89% vs 60%, P = 0.01). Conclusion Administered activity, age, and gland mass were related to the outcome. Radiation absorbed dose, although not significant according to multivariate analysis, may be used as a quantitative parameter in therapy planning, with a target dose of 300 Gy. In cases where a rapid and efficient response to radioiodine treatment is required, adoption of a simplified protocol employing high activities is justified.

Avaliação de atividade inflamatória na osteomielite crônica. Contribuição da cintilografia com anticorpos policlonais

BACKGROUND: Active chronic osteomyelitis or complicating osteomyelitis are difficult to be diagnosed by radiological imaging modalities, such as plain radiograph and CT. They frequently cause increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater infection avidity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99m. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. MATERIAL AND METHODS: 23 bone segments with suspected active chronic osteomyelitis or violated bone osteomyelitis were studied by Tc-99m-IgG scintigraphy. All patients underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs, compared with clinical evaluation and laboratory tests values. RESULTS: Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc-99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%, 88 and 82%. CONCLUSION: Tc-99m-IgG may be usefull in the scintigraphic evaluation of osteomyelitis.OBJETIVO: O diagnostico de osteomielite cronica em atividade ou sobreposta a outras patologias e dificil, pois estas situacoes mascaram os achados radiologicos de infeccao. A especificidade da cintilografia do esqueleto ou com galio-67 tambem e reduzida pela influencia da remodelacao ossea na captacao destes radiofarmacos. Anticorpos policlonais marcados com tecnecio-99m (Tc-99m-IgG) apresentam captacao independente do metabolismo osseo, sendo um dos radiofarmacos em investigacao para avaliacao mais especifica de infeccao. CASUISTICA E METODO: Neste estudo comparou-se a cintilografia com Tc-99m-IgG, cintilografia ossea trifasica e cintilografia com galio-67 no diagnostico da osteomielite cronica em atividade em 23 segmentos osseos; correlacionando-as com dados clinico-laboratoriais e radiologicos. RESULTADOS: Oito dos 23 segmentos foram classificados como infectados, 11 nao infectados e quatro inconclusivos. A sensibilidade e especificidade encontradas para cintilografia ossea, com galio-67 e com Tc-99m-IgG foram, respectivamente, 88 e 36%, 75 e 73%, 88 e 82%. CONCLUSAO: Os resultados sugerem que a Tc-99m-IgG possa ser utilizada no diagnostico da osteomielite cronica em atividade.BACKGROUND Active chronic osteomyelitis or complicating osteomyelitis are difficult to be diagnosed by radiological imaging modalities, such as plain radiograph and CT. They frequently cause increased bone remodeling, leading to nonspecific uptake of Tc-99m-bone scan agents and gallium-67. New radiopharmaceuticals with greater infection avidity are being developed, including the nonspecific polyclonal immunoglobulin (IgG) labeled with technetium-99m. Tc-99m-IgG may be available as a ready to use kit, with no reported side effects, low patient absorbed radiation dose and low cost. MATERIAL AND METHODS 23 bone segments with suspected active chronic osteomyelitis or violated bone osteomyelitis were studied by Tc-99m-IgG scintigraphy. All patients underwent standard three-phase bone scintigraphy using methylene diphosphonate (Tc-99m-MDP), gallium-67 scintigraphy and plain radiographs, compared with clinical evaluation and laboratory tests values. RESULTS Infection was found in 8 sites. Sensitivity and specificity for Tc-99m-MDP, gallium-67 and Tc-99m-IgG scintigraphy were, respectively, 88 and 36%, 75 and 73%, 88 and 82%. CONCLUSION Tc-99m-IgG may be usefull in the scintigraphic evaluation of osteomyelitis.