Search

The etiology of congenital hypothyroidism (CH) is often difficult to identify, owing mainly to limitations in currently available diagnostic tests. Characteristics of the distal femoral epiphyseal (DFE) ossification center may provide important information and help identify some causes of CH. We analyzed the contribution of DFE ultrasonography in the investigation of 11 young infants with positive screening for CH. DFE ultrasonography emerged as a simple test that helped indicate the period of onset of CH and, when associated with clinical history, hormone levels, and thyroid ultrasonography, contributed to suggest the etiology of CH.

Background: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has...

Summary Total thyroidectomy, radioiodine (RAI) therapy, and TSH suppression are the mainstay treatment for differentiated thyroid carcinomas (DTCs). Treatments for metastatic disease include surgery, external-beam radiotherapy, RAI, and kinase inhibitors for progressive iodine-refractory disease. Unresectable locoregional disease remains a challenge, as standard therapy with RAI becomes unfeasible. We report a case of a young patient who presented with unresectable papillary thyroid carcinoma (PTC), and treatment with sorafenib allowed total thyroidectomy and RAI therapy. A 20-year-old male presented with severe respiratory distress due to an enlarging cervical mass. Imaging studies revealed an enlarged multinodular thyroid gland, extensive cervical adenopathy, severe tracheal stenosis, and pulmonary micronodules. He required an urgent surgical intervention and underwent tracheostomy and partial left neck dissection, as the disease was deemed unresectable; pathology revealed PTC. Treatment with sorafenib was initiated, resulting in significant tumor reduction allowing near total thyroidectomy and bilateral neck dissection. Postoperatively, the patient underwent radiotherapy for residual tracheal lesion, followed by RAI therapy for avid cervical and pulmonary disease. The patient's disease remains stable 4 years after diagnosis. Sorafenib has been approved for progressive RAI-refractory metastatic DTCs. In this case report, we describe a patient with locally advanced PTC in whom treatment with sorafenib provided sufficient tumor reduction to allow thyroidectomy and RAI therapy, suggesting a potential role of sorafenib as an induction therapy of unresectable DTC.

Objectives Iodine deficiency during pregnancy is associated with obstetric and neonatal adverse outcomes. Serum thyroglobulin (sTg) and thyroid volume (TV) are optional tools to urinary iodine concentration (UIC) for defining iodine status. This cross-sectional study aims to evaluate the iodine status of pregnant women living in iodine-adequate area by spot UIC and correlation with sTg, TV and thyroid function. Methods Two hundred and seventy-three pregnant women were evaluated at three trimesters. All had no previous thyroid disease, no iodine supplementation and negative thyroperoxidase and thyroglobulin antibodies. Thyroid function and sTg were measured using electrochemiluminescence immunoassays. TV was determined by ultrasonography; UIC was determined using a modified Sandell–Kolthoff method. Results Median UIC was 146 µg/L, being 52% iodine deficient and only 4% excessive. TSH values were 1.50 ± 0.92, 1.50 ± 0.92 and 1.91 ± 0.96 mIU/L, respectively, in each trimester (P = 0.001). sTg did not change significantly during trimesters with median 11.2 ng/mL and only 3.3% had above 40 ng/mL. Mean TV was 9.3 ± 3.4 mL, which positively correlated with body mass index, but not with sTg. Only 4.5% presented with goitre. When pregnant women were categorized as iodine deficient (UIC Conclusions Iodine deficiency was detected frequently in pregnant women living in iodine-adequate area. sTg concentration and TV did not correlate to UIC. Our observation also demonstrated that the Brazilian salt-iodization programme prevents deficiency, but does not maintain iodine status within adequate and recommended ranges for pregnant women.

Made available in DSpace on 2018-12-11T17:18:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Ectopic thyroid results from a migration defect of the developing gland during embryogenesis causing congenital hypothyroidism. But it has also been detected in asymptomatic individuals. This study aimed to investigate the histopathological, functional, and genetic features of human ectopic thyroids. Six samples were histologically examined, and the expression of the specific thyroid proteins was assessed by immunohistochemistry. Two samples were submitted to whole exome sequencing. An oropharynx sample showed immature fetal architecture tissue with clusters or cords of oval thyrocytes and small follicles; one sample exhibited a normal thyroid pattern while four showed colloid goiter. All ectopic thyroids expressed the specific thyroid genes and T4 at similar locations to those observed in normal thyroid. No somatic mutations associated with ectopic thyroid were found. This is the first immature thyroid fetal tissue observed in an ectopic thyroid due to the arrest of structural differentiation early in the colloid stage of development that proved able to synthesize thyroid hormone but not to respond to TSH. Despite the ability of all ectopic thyroids to synthetize specific thyroid proteins and T4, at some point in life, it may be insufficient to support body growth leading to hypothyroidism, as observed in some of the patients. Thyroid Unit Cellular and Molecular Endocrine Laboratory LIM-25 Faculdade de Medicina da Universidade de São Paulo (FMUSP), Avenida Doutor Arnaldo 455, Cerqueira César Adolfo Lutz Institute São Paulo Public Health Service, Av. Dr. Arnaldo 355, Cerqueira César Head and Neck Surgery of Santa Catarina Hospital, Av. Paulista 200, Bela Vista Department of Internal Medicine Botucatu School of Medicine UNESP, Av. Prof. Montenegro, s/n Distrito de Rubião Junior Servicio de Endocrinología Hospital de Pediatría Dr. Juan Garrahan, Combate de los Pozos 1881 Departamento de Cirurgia Na Disciplina de Cirurgia de Cabeça e Pescoço Faculdade de Ciências Médicas UNICAMP, R. Tessália Vieira de Camargo 126 Medicine School Universidade de Fortaleza (Unifor), Av. Washington Soares 1321, Edson Queiroz Postgraduate Program in Biotechnology Universidade Federal de São Paulo (UNIFESP), Pedro de Toledo 669 Thyroid Molecular Sciences Laboratory Universidade Federal de São Paulo Departamento de Ciências Biológicas Postgraduation Programs in Biotechnology and Structural and Functional Biology UNIFESP, Pedro de Toledo 669 Molecular Oncology Center Hospital Sírio-Libanés, Rua Prof. Daher Cutait 69 Department of Internal Medicine Botucatu School of Medicine UNESP, Av. Prof. Montenegro, s/n Distrito de Rubião Junior

Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

DNA methylation regulates gene expression. Aberrant methylation plays an important role in human tumorigenesis. We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non-tumor tissues. Thus, in this study we investigated whether the methylation of the CpG-island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors. Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors (T) along with matched non-tumor (NT) areas were determined by semiquantitative methylation specific-PCR. NIS methylation was detected in all samples. Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status. Highest methylation levels and frequencies were detected in the 5' region of the CpG-island decreasing toward the 3' end. Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression. No quantitative correlation was detected between methylation levels and mRNA expression in any the groups. The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non-homogeneous methylation pattern along the CpG island. Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted.

The main causes of simple diffuse goiter (SDG) and multinodular goiter (MNG) are iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, chronic malnutrition, and lack of selenium, iron, and zinc. Increasing evidence suggests that heredity is equally important. Treatment of SDG and MNG still focuses on L-thyroxine-suppressive therapy surgery. Radioiodine alone or preceded by recombinant human TSH stimulation is widely used in Europe and other countries. Each of these therapeutic options has advantages and disadvantages, with acute and long-term side effects.

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries. Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.

Treatment of multinodular goiters (MNGs) is highly controversial. Radioiodine (RAI) therapy is a nonsurgical alternative for the elderly who decline surgery. Recently, recombinant human thyrotropin (rhTSH) has been used to augment RAI uptake and distribution. In this study, we determined the outcome of 30 mCi RAI preceded by rhTSH (0.1 mg) in euthyroid (EU) and hyperthyroid (subclinical/clinical) patients with large MNGs.This was a prospective cohort study. Forty-two patients (age, 43-80 years) with MNGs were treated with 30 mCi RAI after stimulation with 0.1 mg of rhTSH. Patients were divided into three groups, according to thyroid function: EU (n = 18), subclinically hyperthyroid (SC-H, n = 18), and clinically hyperthyroid (C-H, n = 6). All patients underwent a 90-day low-iodine diet before treatment, and those with clinical hyperthyroidism received methimazole 10 mg daily for 30 days. Serum TSH, free thyroxine (FT4), total triiodothyronine (TT3), and thyroglobulin were measured at baseline and at 24, 48, 72, 168 hours, and 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. Thyroid volume was assessed by computed tomography at baseline and every 6 months.Patients had high iodine urinary excretion (308 +/- 108 microg I/L) at baseline. TSH levels at baseline were within the normal range (1.5 +/- 0.7 microU/mL) in the EU group and suppressed (0.3 microU/mL) in the SC-H and C-H groups. After rhTSH, serum TSH peaked at 24 hours reaching 12.4 +/- 5.85 microU/mL. After RAI administration, patients in both hyperthyroid groups had a higher increase in FT4 and TT3 compared with those in the EU group (p0.001). Thyroglobulin levels increased equally in all three groups until day 7. Thyroid volume decreased significantly in all patients. Side effects were more common in the SC-H and C-H groups (31.4% and 60.4%, respectively) compared with EU patients (17.8%). Permanent hypothyroidism was more prevalent in the EU group (50%) compared with the SC-H (11%) and C-H (16.6%) groups.Patients with MNG may have subclinical and clinical nonautoimmune iodine-induced hyperthyroidism. Despite a low-iodine diet and therapy with methimazole, hyperthyroid patients have a significantly higher increase in FT4 and TT3 levels after RAI ablation. This can lead to important side effects related mostly to the cardiac system. We strongly advise that patients with SC-H and C-H be adequately treated with methimazole and low-iodine diet aiming to normalize their hyperthyroid condition before rhTSH-stimulated treatment with RAI.

OBJECTIVES: To evaluate the prevalence of thyroid dysfunction in elderly cardiac patients in an outpatient setting. SUBJECTS AND METHODS: A total of 399 consecutive patients (268 women, age range 60–92 years) who were followed at Heart Institute were evaluated for thyroid dysfunction with serum free T4, TSH, anti-Peroxidase antibodies, urinary iodine excretion measurements and thyroid ultrasound. RESULTS: Hyperthyroidism (overt and subclinical) was present in 29 patients (6.5%), whereas hypothyroidism (overt and subclinical) was found in 32 individuals (8.1%). Cysts were detected in 11 patients (2.8%), single nodules were detected in 102 (25.6%), and multinodular goiters were detected in 34 (8.5%). Hashimoto’s thyroiditis was present in 16.8% patients, most of whom were women (83.6%). The serum TSH increased with age and was significantly higher (p= 300 μg/L) was observed in one-third of patients (30.8%). CONCLUSIONS: Elderly patients have a higher prevalence of both hypo- and hyperthyroidism as well as thyroid nodules when compared with the general population. About one-third of the older patients had elevated urinary secretion of iodine and a higher prevalence of chronic Hashimoto’s thyroiditis. It is recommended that ultrasonographic studies, tests for thyroid function and autoimmunity should be evaluated in elderly patients.

OBJECTIVE: To extend the molecular analysis of the IVS30+1G>T intronic thyroglobulin (TG) mutation, and to report the eleven year follow-up of the affected patients. METHOSD: Two siblings with severe congenital hypothyroidism with fetal and neonatal goiter, harboring the IVS30+1G>T mutation were included. Nodular and non-nodular thyroid tissue specimens were collected. Specific thyroid genes expression was evaluated by real-timePCR and by immunohistochemistry. RESULTS: In non-nodular tissue specific thyroid genes mRNA were reduced when compared to normal thyroid sample. In the nodule, TPO and NIS expression was very low. Microscopic examinations showed very large follicular-lumina and swollen vesicles of endoplasmatic-reticulum. Strong cytoplasmatic and low follicular-lumen TG immunostaining were detected. Intracellular NIS, membrane TPO and TSHR immunostaining had higher positivity in non-nodular sample. Both patients had a long-term adequate developmental outcome, besides one patient have been lately-treated. CONCLUSIONS: IVS30+1G>T mutation not only lead to very enlarge endoplasmatic-reticulum, but also to alterations of specific thyroid genes expression. The clinical evolution of patients harboring these mutations strengthen the concept of the influence of environment, like iodine nutrition, to determine the final phenotypic appearance.

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.

The objective of the study was to determine the diagnostic accuracy of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in the preoperative diagnosis of thyroid nodules with indeterminate fine-needle aspiration biopsy results.Forty-two consecutive patients with thyroid nodules with indeterminate cytological results participated in this study. Abnormal (18)F-FDG PET uptake was assessed visually and by measuring the maximum standardized uptake value (SUVmax) in thyroid topography. All these results were compared with the final pathological results.The presence of focal uptake correlated with a greater risk of malignancy (P = 0.018). All 11 malignant nodules had focal uptake (sensitivity of 100%). Of the 31 patients with benign nodules, there were 19 with positive uptake (specificity of 38.7%). The pre-PET probability of cancer was 26.2% (11 of 42), and this probability increased to 36.7% after PET for those patients whose exam showed focal uptake (11 of 30). The preoperative use of (18)F-FDG PET would result in a significant reduction (39%, 12 of 31) in the number of thyroidectomies performed in patients with benign lesions. SUVmax could not improve this degree of accuracy. There was no correlation between thyroid nodule size and SUVmax value (P = 0.96). Patients with carcinomas were younger than patients with benign lesions (P = 0.048). There was no other clinical, laboratory, or ultrasonographic variable related to malignancy.(18)F-FDG PET provides high sensitivity to malignant lesions and may be a potentially useful tool in the evaluation of thyroid nodules with indeterminate cytological findings. For these nodules the number of unnecessary thyroidectomies in a hypothetical algorithm using (18)F-FDG PET would be reduced by 39%.

Os nódulos tireóideos são encontrados em grande parte da população, mas somente 5 a 10% são malignos. A ultra-sonografia da tireóide, por ser um método simples, não-invasivo e apresentar boa correlação com os aspectos macroscópicos da glândula tireóide, é cada vez mais utilizada para identificar os nódulos que apresentam maior risco de malignidade. A presença de algumas características ultra-sonográficas como hipoecogenicidade, microcalcificações, contornos irregulares e vascularização central ao Doppler, aumenta o risco de malignidade da lesão. Por outro lado, nódulos que apresentam características ultra-sonográficas benignas, como hiperecogenicidade e aspecto misto semelhante a uma esponja, apresentam concordância com a citologia, com valor preditivo negativo de 96,6%. É importante, pois, examinarmos e classificarmos todas as lesões nodulares para selecionarmos aquelas suspeitas para a biópsia, principalmente em uma tireóide multinodular. A ultra-sonografia também apresenta alta sensibilidade para identificar gânglios cervicais suspeitos no seguimento de pacientes com carcinoma da tireóide, mesmo quando a PCI é negativa e a tireoglobulina (Tg) sérica, indetectável. É recomendável a dosagem da Tg no lavado da agulha da punção, pois esta tem-se mostrado mais sensível que a citologia no diagnóstico de metástase cervical, principalmente quando existe conteúdo líquido, e não é afetada pela presença de anticorpos anti-Tg.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:58:43Z No. of bitstreams: 1 S0004-27302006000300019.pdf: 83972 bytes, checksum: 892aaea7a03ec59d0984eaf5201d2b42 (MD5) Made available in DSpace on 2013-08-22T18:58:43Z (GMT). No. of bitstreams: 1 S0004-27302006000300019.pdf: 83972 bytes, checksum: 892aaea7a03ec59d0984eaf5201d2b42 (MD5) Previous issue date: 2006-06-01 Made available in DSpace on 2013-09-30T19:54:41Z (GMT). No. of bitstreams: 2 S0004-27302006000300019.pdf: 83972 bytes, checksum: 892aaea7a03ec59d0984eaf5201d2b42 (MD5) S0004-27302006000300019.pdf.txt: 34663 bytes, checksum: 0ded15e711cb48b77106764e342b0fb4 (MD5) Previous issue date: 2006-06-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:14:13Z No. of bitstreams: 2 S0004-27302006000300019.pdf: 83972 bytes, checksum: 892aaea7a03ec59d0984eaf5201d2b42 (MD5) S0004-27302006000300019.pdf.txt: 34663 bytes, checksum: 0ded15e711cb48b77106764e342b0fb4 (MD5) Made available in DSpace on 2014-05-20T15:14:13Z (GMT). No. of bitstreams: 2 S0004-27302006000300019.pdf: 83972 bytes, checksum: 892aaea7a03ec59d0984eaf5201d2b42 (MD5) S0004-27302006000300019.pdf.txt: 34663 bytes, checksum: 0ded15e711cb48b77106764e342b0fb4 (MD5) Previous issue date: 2006-06-01 A incidência do câncer diferenciado da tiróide vem aumentando há várias décadas no Brasil, assim como em todo o mundo. A popularização de métodos diagnósticos sensíveis e de uso relativamente simples tem contribuído para o diagnóstico cada vez mais freqüente de carcinomas de pequeno tamanho. Uma parte destes tumores ocorre em pacientes denominados de baixo risco, que poderiam se beneficiar de estratégias de conduta menos agressivas. Entretanto, a definição de baixo risco ainda é confusa e não existem meios seguros para distinguir os pacientes que evoluirão de forma pior dos demais. Por outro lado, o uso de novos métodos de acompanhamento vem mudando a maneira de conduzir estes casos. Um grupo multidisciplinar que inclui pesquisadores básicos, endocrinologistas, médicos nucleares, cirurgiões e patologistas endócrinos reviu a literatura pertinente e, com base em sua experiência, propõe algumas normas de conduta no carcinoma diferenciado da tiróide chamado de baixo risco em nosso meio. 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. Universidade Estadual de Campinas/UNICAMP Faculdade de Ciências Médicas Departamento de Clínica Médica Universidade Estadual de Campinas/UNICAMP Faculdade de Ciências Médicas Departamento de Cirurgia Universidade Estadual de Campinas/UNICAMP Faculdade de Ciências Médicas Departamento de Anatomia Patológica Sociedade Brasileira de Biologia e Medicina Nuclear Santa Casa de Misericórdia de São Paulo Universidade de São Paulo/FMUSP Faculdade de Medicina Departamento de Clínica Médica Universidade de São Paulo/FMUSP Faculdade de Medicina Centro de Medicina Nuclear Universidade de Santo Amaro/ UNISA Faculdade de Medicina Departamento de Cirurgia Universidade de São Paulo Instituto de Ciências Biológicas Departamento de Fisiologia e Biofísica Universidade de São Paulo Instituto de Ciências Biológicas Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica

OBJECTIVE Patients with very large multinodular goitres, frequently found among elderly people, often suffering from cardiovascular or other disabling disorders, may be considered as unsuitable for surgery. We have evaluated the feasibility of relatively high-dose 131I therapy in such patients. As subclinical or clinical hyperthyroidism is commonly found in these patients, associated with a low radioiodine (RAI) uptake at 24 h, we pretreated a group of patients with a single intramuscular injection of recombinant human TSH (rhTSH 0.45 mg) in order to increase the uptake of the therapeutic dose of RAI. DESIGN AND PATIENTS Forty-one patients with large, long-standing multinodular goitres, were recruited for this study. After a careful and detailed clinical and laboratory evaluation, 34 patients (28 women, six men) were included and randomly assigned to group 1 (control, n = 17, 15 women, two men, age 63.1 +/- 11.2 years) receiving only RAI. Patients in group 2 (n = 17, 13 women, four men, age 63.6 +/- 12.3 years) received the therapeutic dose of RAI, having been pretreated (24 h) with 0.45 mg of rhTSH. Both groups of patients were submitted to a low iodine diet, 4-6 months before RAI treatment, while seven thyrotoxic patients also received methimazole (40 mg/day) until they reached euthyroidism. Ultrasonographic studies were performed for all patients and fine-needle aspiration biopsy (FNAB) were performed on one or two nodules before RAI treatment. RAI was given as a single oral dose to the hospitalized isolated patients. Blood samples for thyroid function tests and serum thyroglobulin (Tg) were collected daily during the first week following RAI treatment, and at 1, 3, 6, 9 and 12 months thereafter. MEASUREMENTS Goitre volume was estimated by computed tomography scan. Thyroid function tests (total T3, free T4, TSH and serum Tg) were assayed with commercial kits. Urinary excretion of iodine was assayed by the Sandell-Kolthoff method. RESULTS After the RAI therapeutic dose, serum thyroid function tests were carried out daily for the first week and then on a monthly basis (1, 3, 6, 9 and 12 months). Serum TSH levels rose to a peak level of 45.9 +/- 19.1 mU/l (24 h) in group 2 returning to normal at 72 h. Free T4 serum concentrations rose significantly to 59.35 +/- 21.61 pmol/l at 48 h (in group 2) returning to normal at 7 days. Similarly, serum TT3 also peaked above normal levels only in group 2 (6.12 +/- 1.89 nmol/l) at 24 h. Serum Tg increased in both groups (significantly higher in group 2) and remained elevated during the following 12 months. Both groups had a significant reduction in goitre volume at 12 months (group 2: 57.8%vs. group 1: 39.7%, P < 0.05). Hypothyroidism was detected after RAI treatment, respectively, in 21.4% (group 1) and 64.7% (group 2), of the patients at 12 months. CONCLUSIONS Our results indicate that the use of hTSH increased the efficacy of the RAI therapeutic dose. This was basically due to an increased uptake of the radionuclide (as a consequence of the higher serum TSH levels) and a more extensive distribution of 131I within the nodules of the multinodular goitre. A more intense radiation effect was reflected in there being a higher output of serum Tg and thyroid hormones (group 2). As a consequence this group had a significantly higher reduction of the goitre volume. Also incidence of hypothyroidism post-RAI was significantly higher in group 2. We concluded that pretreatment with rhTSH in elderly patients with large multinodular goitres increases the uptake of the RAI therapeutic dose, thereby significantly reducing the multinodular goitre volume and relieving the compressive symptoms with relatively few side-effects.

O objetivo deste estudo foi avaliar a nossa classificação ultra-sonográfica dos nódulos tireóideos, baseada na ecoestrutura, ecogenicidade, calcificação, contornos e análise do restante do parênquima. De janeiro de 1998 a janeiro de 2002, 2468 pacientes portadores de nódulos tireóideos foram encaminhados ao nosso serviço para realização de ultra-sonografia e punção aspirativa por agulha fina guiada pelo ultra-som (US-PAAF). De 1039 nódulos considerados benignos ao ultra-som, 998 (96,05%) também apresentaram citologia benigna, 37 (3,6%) tiveram citologia suspeita e somente 4 (0,4%) tiveram citologia maligna. De 153 nódulos considerados suspeitos ao ultra-som, 20 (13,1%) tiveram citologia suspeita e 88 (57,5%) tiveram citologia maligna. Dos 71 nódulos suspeitos ao ultra-som submetidos à cirurgia, 67 (94,3%) tiveram diagnóstico anatomopatológico maligno. Já, dos 58 nódulos considerados benignos, 56 (96,6%) tiveram diagnóstico anatomopatológico benigno. Concluímos que a US-PAAF deve ser realizada em nódulos classificados como indeterminados ou suspeitos ao ultra-som. Nódulos classificados como benignos podem ser acompanhados periodicamente.

In thyroid tumors, reduced radioiodine uptake is associated with worse patient outcome concomitantly with low sodium/iodide symporter (NIS) mRNA expression. Previous studies showed that CpG-island methylation in the NIS proximal promoter does not correlate with mRNA expression.The aim of the study was to identify new CpG-islands within the NIS 5'region and investigate the involvement of their methylation in NIS expression.DNA was obtained from 30 pairs of thyroid samples: tumor (T) and surrounding nontumor (NT) samples. All T samples had reduced NIS mRNA expression compared to NT samples.Methylation degree was quantified by bisulfite sequencing, and NIS expression by real-time PCR and Western blot. Reporter gene assays were performed to determine CpG-island functionality. Tumor cell cultures were treated with 5-Aza demethylating agent to determine NIS expression, methylation status, and (125)I uptake.We identified a new CpG-island2 with 14 CpG sites, located -2152/-1887 relative to ATG site. CpG-island2 was hypermethylated in T compared to NT samples, in both benign and malignant tumor groups. There was a significant inverse correlation between NIS mRNA expression and degree of CpG-island2 methylation in NT and T samples. This sequence increased the expression of a reporter gene; thus, it was considered a new enhancer. Cell culture treatments with 5-Aza reduced CpG-island2 methylation levels concomitantly with restoration of NIS mRNA and protein expression and (125)I uptake.We identified a new distal enhancer, NIS distal enhancer, that regulates gene expression through DNA methylation. This enhancer is hypermethylated in T compared to NT samples and is associated with decreased NIS expression in tumors. This epigenetic deregulation may be an early event in tumorigenesis.

O objetivo dessa apresentação é discutir o Carcinoma Insular da Tireóide, uma forma rara de neoplasia com características clínicas e histológicas bastante peculiares. Inicialmente, será apresentado o caso seguido de uma breve discussão clínica. Posteriormente, serão discutidos aspectos histológicos e IHQs e os marcadores de agressividade desse tipo de tumor, seguindo-se uma discussão aberta com outros membros do serviço.

AVALIACAO E CONDUTA DE UM PACIENTE portador de um nodulotireoideo ainda e assunto bastante controverso. E dificil elaborar ummodelo que possa ser aplicado a todos os casos. Nem sempre o que e me-lhor para um paciente o e para outro, pois devemos analisar cada casoindividualmente e varios fatores (idade, aspecto socio-economico,doencas concomitantes, motivos pessoais ou familiares) vao influenciarna escolha do tratamento adequado para cada caso. Para finalidadedidatica, compilamos um resumo dos principais topicos utilizados paradiagnostico e opcoes de tratamento dos nodulos. Finalmente, sugerimosum guia pratico para auxiliar a conduta frente a um paciente portador denodulo da tireoide.Cintilografia e captacao da tireoide com radioiodo ou tecnecio:Indicado na suspeita clinica e laboratorial de nodulo autonomo.Avaliacao Ultra-sonografica:Em nossa opiniao, deve ser realizado rotineiramente com a finali-dade de confirmar o diagnostico clinico, determinar as caracteristicasmacroscopicas do nodulo (contorno, ecogenicidade, presenca de halohipoecoico, areas liquidas ou calcificacoes) e selecionar os nodulos sus-peitos para a puncao aspirativa por agulha fina (PAAF).Classificacao ultra-sonografica dos nodulos tireoideos (tabela 1):Grau I (score 1): pequena imagem anecoica arredondada, com-pativel com cisto de tireoide.Grau II (score 2): nodulo de textura mista e imagens nodularessolidas isoecoicas ou hiperecoicas de textura homogenea, acompanhadasou nao de calcificacoes grosseiras, componente liquido e com o restante doparenquima de textura homogenea, sao compativeis com Bocio ColoideAdenomatoso; nodulo isoecoico, de textura homogenea, com halohipoecoico periferico em tireoide de volume e ecogenicidade normais esugestivo de Adenoma Folicular.Grau III (score 3): nodulo hipoecoico, de contorno regular, semcalcificacoes e nodulos cisticos com componente solido sao consideradosduvidosos.Grau IV (score 4): nodulo solido hipoecoico, de contorno impre-ciso e com microcalcificacoes e considerado suspeito para malignidade esugestivo de câncer da tireoide.

Diagnostico dos nodulos tireoideos baseado na avaliacao ultra-sonografica e citologica combinada

Struma ovarii is an infrequent ovarian tumor, and there are only few reports with detailed data of thyroid function. In several cases, malignant struma ovarii have been shown to produce hyperthyroidism, but there is no reported case of hypothyroidism following struma ovarii tumor resection. A 62-year-old white woman underwent right ovary resection that had a pathologic diagnosis of struma ovarii. After 6 days, she developed weakness, myalgia, somnolence, nausea, and arterial hypotension. Laboratory tests showed a high level of thyroid-stimulating hormone (TSH) and a decreased level thyroxin. Thyroxin replacement therapy was initiated, and the patient became completely asymptomatic. This is the first reported case of a previously asymptomatic woman who developed a definite clinical hypothyroidism after resection of a struma ovarii tumor.

661 THE EVALUATION OF IODINE DEFICIENCY DISORDERS (IDD) in Europe was recently conducted using an adapted Thyromobil vehicle equipped with ultrasound apparatus, a computer unit, and a freezer to store specimens and supplies (1). The Thyromobil traveled from one country to another, collecting data on thyroid volume, urinary excretion of iodine, and content of iodine in the local source of salt. The excellent results of the Thyromobil project in Europe encouraged

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.

Esse artigo tem o objetivo de discutir o papel da tomografia por emissão de pósitrons (PET) com 18F-FDG na avaliação pré-operatória de pacientes com nódulos de tireóide com citologia indeterminada. Para o cálculo da sensibilidade, foram selecionados todos os estudos com pacientes com carcinoma de tireóide. Para o cálculo da especificidade, foram selecionados apenas estudos desenhados para avaliação dos pacientes com nódulos com citologia indeterminada. O achado de captação focal na PET-18F-FDG relacionou-se com a presença de carcinoma de tireóide na maioria dos estudos. A sensibilidade do exame foi bastante alta na detecção de malignidade tireoidiana, porém sua especificidade variou de 0% a 66%, sendo de 39% em estudo brasileiro. Concluindo, os estudos indicam que a PET-18F-FDG pode reduzir o número de tireoidectomias desnecessárias em pacientes com nódulos de tireóide com citologia indeterminada. Entretanto, o percentual relativamente elevado de resultados falso-positivos, o alto custo, a baixa disponibilidade do exame em países em desenvolvimento e a pouca experiência clínica ainda limitam o uso da PET-18F-FDG com essa finalidade. The aim of this article is to discuss the role of 18F-FDG Positron Emission Tomography (PET) in the preoperative evaluation of patients with cytologically indeterminate thyroid nodules. All studies with patients with thyroid cancer were selected to the calculation of sensitivity. Only studies aiming to evaluate patients with thyroid nodules whose cytological result was indeterminate were selected to establish the specificity. The finding of focal 18F-FDG uptake at PET was associated with the presence of thyroid malignancy in most of the studies. The sensitivity of the exam to the detection of thyroid malignancy was extremely high, but the specificity varied from 0 to 66%. In our experience, the specificity was 39%. In conclusion, the studies suggest that 18F-FDG PET can reduce the number of unnecessary thyroidectomies performed in patients with cytologically indeterminate thyroid nodules. However, the relatively high percentage of false positive results, the high costs, the low availability of this exam in developing countries and the low clinical experience still restrict the use of 18F-FDG PET when recommended with this aim.

ObjectiveTo evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40–100 mg/kg salt).DesignThis was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in São Paulo, Brazil, and conducted during the first semester of 2004.MethodsThyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations.ResultsAt the time the study was conducted, table salt iodine concentrations were within the new official limits (20–60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion was excessive (above 300 μg/l) and, in 14.1%, it was higher than 400 μg/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085).ConclusionsFive years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake.

PURPOSE: To evaluate the prevalence of chronic autoimmune thyroiditis in 2 urban areas of metropolitan São Paulo (Brazil): Polo Area neighboring a large petrochemical complex and São Bernardo Campo Area (control area). SUBJECTS AND METHODS: Subjects were randomly included from the adult population (20 to 70 years of age) of both genders (women 80%, men 20%) who voluntarily agreed to participate. From the Polo Area, in the vicinity of a large petrochemical industrial complex, 409 subjects were included; from the control area (São Bernardo Campo Area) 420 individuals were included. All subjects were clinically examined, and a detailed record of past thyroid illness and medications was obtained. Ultrasonographic studies were performed using a portable GE Medical Systems apparatus. Blood samples were obtained for free T4, serum TSH, and serum anti-thyroid peroxidase autoantibodies. Urine specimens were collected in Monovette syringes for assaying iodine content. Salt samples were collected at households, and the iodine content was measured. RESULTS: Chronic autoimmune thyroiditis was diagnosed both echographically (marked hypoechogenicity) and immunologically (presence of autoantibodies against thyroid peroxidase). In the Polo Area, 15.6% of the examined population had chronic autoimmune thyroiditis, and in the control area (São Bernardo Campo Area), 19.5% of the population had evidence of chronic autoimmune thyroiditis (P >; 0.057, not significant). The prevalence of hypothyroidism was 4.9% in the Polo Area and 8.3% in the São Bernardo Campo Area (P = 0.0461 significant). Taking the 2 populations together, 6.6% had hypothyroidism (about one third of these patients were on L-T4 treatment). The mean thyroid volume was 11.2 mL. Domestic salt had a normal concentration of iodine (35.5 + 6.61 mg/kg). Urinary excretion of iodine was above 300 µg Iodine/L in 58.5% of the total population. CONCLUSION: The high iodine intake (above 300 µg Iodine/L of urine) that was present from 1998 through 2005 may be related to a higher prevalence of chronic autoimmune thyroiditis in both areas that were studied. There was no apparent or documented relationship of chronic autoimmune thyroiditis prevalence to the proximity to the petrochemical complex. OBJETIVO: Analisar a prevalência populacional de tireoidite crônica autoimune (tireoidite de Hashimoto) na área vicinal ao Polo Petroquímico de Capuava comparativamente a área controle em São Bernardo Campo. CASUÍSTICA E MÉTODOS: Em ambas as áreas urbanas foram incluídos, aleatoriamente, indivíduos adultos que, de forma voluntária, concordaram em participar do estudo, estratificado por idade (20 a >; 70 anos) e sexo (mulheres 80%, homens 20%). Na área Polo foram incluídos 409 indivíduos e na área controle (São Bernardo Campo) 420 pessoas (sem diferenças significativas quanto a idade e sexo). Na área Polo 15,6% apresentava sinais ecográficos e de positividade para anticorpos anti TPO, confirmando tireoidite crônica autoimune (TCA) comparativamente a 19,5% na área controle (p >; 0,05, NS). A presença de hipotiroidismo foi confirmada em 4,9% da população na área Polo e 8,3% na área controle (São Bernardo Campo) (p = 0,046, significativo). No conjunto 6,63% dos pacientes com TCA apresentavam hipofunção tireóidea. A excreção urinária de iodo ultrapassou 300 mcg Iodo/L de urina em 58,5% de ambas populações. O sal coletado nas casas dos examinados apresentava concentração normal de iodo (35,5 + 6,6 mg I/Kg de sal). CONCLUSÕES: A maior prevalência de tireoidite crônica autoimune em ambas as áreas é, provavelmente, decorrente da elevada ingestão nutricional de iodo durante o quinqüênio que precedeu esta pesquisa (1998-2004). A suposta conexão epidemiológica de maior prevalência epidemiológica de TCA com vicinidade com o Polo Petroquímico de Capuava é improvável.

O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100µg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2%) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60% dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.

A iodação do sal é eficiente no combate às doenças decorrentes da deficiência de iodo, sendo empregada em todo território nacional desde 1995. O Estado de São Paulo é considerado uma área ioda-suficiente. Para avaliar a ingesta de iodo, foram selecionados aleatoriamente 844 escolares entre 6 e 14 anos, de seis regiões do Estado. Foram avaliados, sob o ponto de vista ecográfico da tireóide, 423 meninos e 421 meninas. Os volumes da glândula tireóide elevaram-se progressivamente com a idade, guardando correlação positiva e significativa com a superfície corporal. Cerca de 1,6% dos escolares apresentava bócio. Nódulos, cistos, hemiagenesia foram detectados em 1,4% dos examinados. Notamos excessiva excreção urinária de iodo nesta população, cerca de 53% eliminou acima de 300µg Iodo/L e valores acima de 600µgI/L foram encontrados em 21% dos escolares. As amostras de sal doméstico apresentavam valores entre 28,1 e 63,3mg Iodo/kg de sal. Concluímos que a população escolar do Estado de São Paulo apresenta excessiva ingestão diária de iodo, a qual, extrapolada para a população em geral, pode induzir várias alterações da função tireóidea, como hipertiroidismo subclínico (em idosos) e tireoidite crônica autoimune na população adulta, em geral. We have examined, by ultrasonographic studies, the thyroid gland of 844 schoolchildren, aged between 6 and 14 years old (423 girls, 421 boys). There was a progressive increase of the thyroid volume with aging with a positive and significant correlation with the body surface area. The presence of enlarged thyroid gland was rarely seen, being present in only 1.6% of the studied cohort. A few thyroid gland abnormalities were noticed such as hemiagenesia (4 children), nodules and cysts and hypoechogenicity (total: 1.4% of all subjects examined). It was clearly demonstrated that the urinary excretion of iodine was elevated being above 300ug Iodine/L in 53% of the schoolchildren examined. Assays for the iodine concentration in the domestic salt samples revealed values between 28.1 and 63.3mgI/kg of salt. We concluded that the schoolchildren population of the State of Sao Paulo may be under an excessive daily ingestion of iodine. This may induce, if extrapolated to the general population, subclinical hyperthyroidism in the elderly and possibly an increment in the prevalence of chronic autoimmune thyroiditis.

A bioequivalência e biodisponibilidade das preparações comerciais de L-tiroxina podem apresentar diferenças significativas entre si. O objeto do presente trabalho foi comparar variáveis séricas tireóideas (T4 e T3 totais, T4 livre e TSH endógeno) em pacientes previamente tireoidectomizados (há mais de 5 anos) e sem evidência clínica ou ecográfica de tecido glandular cervical remanescente. Os referidos parâmetros foram medidos, por 15 dias, a intervalos de tempo regulares, durante administração de solução oral de L-tiroxina (100µg), presumivelmente de absorção e biodisponibilidade ideais. Comparou-se, em seguida, a oscilação das mesmas variáveis com duas outras preparações comerciais, sob forma de comprimidos de L-tiroxina (LT4A e LT4B) nas doses de 100µg/dia e a seguir 200µg/dia. Não se observou diferença significativa entre a solução oral e as duas preparações comerciais nos vários tempos de medida. Tampouco houve diferença significativa entre os comprimidos de L-T4A e L-T4B em doses de 100µg ou de 200µg/dia. Concluímos que ambas as preparações apresentam biodisponibilidade e bioequivalência adequadas nas condições utilizadas neste estudo. A major issue influencing prescribing patterns of physicians has been the relative bioavailability and bioequivalence of commercial levothyroxine preparations. Some studies have suggested similar bioequivalence between various L-T4 tablets while other reports have found differences. Some of these studies have been criticized for methodological defects in patients' selection or study design, which have become appreciated only in retrospect. Moreover the US Pharmacopeia has proposed that commercial tablets of L-T4 should be tested for its dissolution in two different solutions. Each manufacturer should periodically test batches of tablets as indicated. In the present study, we have compared serum thyroid function parameters (total T4, total T3, free T4, and serum TSH) in previously totally thyroidectomized patients, without sonographic evidence for reminiscent thyroid tissue in the cervical area. The above parameters were measured, as function of time, for 15 days of either an oral solution of L-T4 (100µg) or tablets of L-T4A and L-T4B (100µg/tablet). There was no significant difference between the various parameters, in relation to time, for each of the different preparations. Moreover L-T4A tablets did not differ from L-T4B tablets, when those parameters were tested, either at the concentration of 100 or 200µg/day. We conclude that the two oral formulations of L-thyroxine have similar bioavailability and bioequivalence under the present experimental conditions.

An adult male patient (38 yr old) with a large congenital goiter with hypothyroidism was suspected of having a defective oidide (I−) transport mechanism based on low thyroid uptake and a very low salivary/plasma ratio. Moreover the high serum levels of TSH (104 μU/mL) declined to 7.2 μU/mL with a corresponding normalization of serum total T4 concentration, after 40 d of treatment with Lugol’s solution (6 mg I/d). Thyroid surgery was performed because a fine-needle aspiration biopsy of a nodule revealed atypical cells associated with the presence of a large compressive goiter (150 g). Pathologic examination indicated histological findings compatible with the hyperplastic pattern with predominant microfollicular aspect. Immunostaining for other specific thyroid proteins, thyroid peroxidase (TPO) and Tg, indicated normal expression of both transcripts. Electron microscopy (×13,000) showed the ultrastructural aspects of a hyperactive follicular cell with folding of the basal membrane. Sequencing of the entire sodium/iodide (Na/I) symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide 1163 with an adenine, resulting in a stop signal at codon 272. This nonsense mutation produces a truncated NIS symporter protein without iodide transport activity. Although the propositus is homozygotic for the NIS-272X expression of one normal allele in the heterozygotic son, mother, and paternal aunt is sufficient to maintain normal thyroid function.

Purpose Our objective was to establish thyroid volume by sonography in Brazilian schoolchildren and to correlate thyroid volume with anthropometric characteristics. Methods Sonographic studies of thyroid volume were conducted in 1,977 schoolchildren (6–14 years old) from 21 villages and towns in Central Brazil. Iodine concentration was analyzed in urine specimens and in salt samples obtained from the children's homes. Thyroid volumes were also compared with volumes reported for other countries. Results Age, height, and weight correlated with thyroid volume. Thyroid volumes for boys and girls were generally lower than those obtained in Europe and comparable to those obtained in Malaysia and Iran. Urinary iodine excretion was considered elevated in about half of the Brazilian schoolchildren, and the iodine content of salt samples was more than 50 ppm in 58%. Conclusions We observed relatively smaller thyroid gland volumes in Brazilian schoolchildren as compared with those reported in Europe. This was apparently due to a higher iodine intake in our population. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:226–231, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.10060

In this article we describe detailed pathological and molecular genetics studies in a consanguineous kindred with Pendred's syndrome. The index patient was a 53-year-old female patient with congenital deafness and goiter. Her parents were first-degree cousins. She had a large goiter (150 g) that had been present since childhood. One of her sisters and a niece are also deaf and have goiter as well. The presence of Pendred's syndrome was confirmed by a positive perchlorate test and the demonstration of a Mondini malformation. Thyroid function tests (under levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin [TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L (0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was found to have invaded adjacent tissues. The histopathological findings were consistent with a follicular carcinoma with areas of anaplastic transformation and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 MBq) and received suppressive doses of LT4. Postoperatively, the serum thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). The patient died of a sudden severe episode of hemoptysis. Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule. We concluded that prolonged TSH stimulation because of iodine deficiency or dyshormonogenesis in combination with mutations of oncogenes and/or tumor suppressor genes, may result in the development of follicular thyroid carcinomas that undergo transformation into anaplastic cancers. It is likely that these pathogenetic mechanisms have been involved in the development of aggressive metastatic thyroid cancer in this unusual patient with Pendred's syndrome.

Two unrelated families (CA and NA) in which an iodide organification defect (lOD) was present in two siblings of each family were studied. These patients had congenital goiters with hypothyroidism and a positive perchlorate discharge test. Examination of the thyroid tissue revealed no thyroid peroxidase (TPO) activity. Histologic findings were consistent with a microfollicular pattern of hyperplasia. Moderate cellular atypia was present, characterized by nuclear pleomorphism and hyperchromatism. Full length thyroglobulin was purified by gel filtration, but was not iodinated. Immunohistochemical studies using a polyclonal anti-human thyroid peroxidase (hTPO) antibody confirmed the presence of immunoreactive TPO protein in the thyroid tissues. Samples of normal and affected individuals were studied with respect to the presence of various fragments using TPO probes of varying sizes. The two affected siblings from family CA were homozygous for fragments 3.9, 4.6, and 7.0 kb (8g111) and 2.3 and 2.9 kb (Ta ql), whereas the parents were heterozygous. In the other family (NA), the Bg/ll digestion and TPO-31 hybridization revealed an interesting and informative polymorphism. The parents showed two different polymorphic patterns: the father had a 5.0/4.6 kb pattern and the mother a 4.7/4.5 kb pattern. However, the two affected siblings showed the same heterozygotic allelic pattern at 4.5/4.6 kb. The restriction fragment length polymorphism detected in these two families suggests an association between the TPO gene and an lOD. Results suggest that in these dyshormonogenetic tissues an altered TPO protein molecule is being synthesized, without detectable in vitro activity, but visible by immunostaining techniques in the goitrous tissue. Mutations in the TPC gene sequence are most likely associated with these changes.