Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?

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 been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.

Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer.

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.

Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer

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.

Hypermethylation of a New Distal Sodium/Iodide Symporter (NIS) enhancer (NDE) is associated with reduced NIS expression in thyroid tumors.

CONTEXT: 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. OBJECTIVES: 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. DESIGN: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Approach to and treatment of goiters.

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.

High prevalence of side effects after recombinant human thyrotropin-stimulated radioiodine treatment with 30 mCi in patients with multinodular goiter and subclinical/clinical hyperthyroidism.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.001). 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. CONCLUSIONS: 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.

Excessive iodine intake and ultrasonographic thyroid abnormalities in schoolchildren.

High nutritional levels of iodine may induce a higher prevalence of autoimmune thyroiditis, hypothyroidism, goiter, as well as hyperthyroidism, mostly in the elderly. This study assessed thyroid volume and ultrasonographic abnormalities as well as urinary iodine excretion (UIE) in 964 schoolchildren living in an iodine-sufficient area in southern Brazil. Thyroid volume correlated with age and body surface area in boys and girls. In 76.8% of the children, UIE was above 300 microg/l, with higher levels among boys compared to girls (484.2 microg/l vs 435.3 microg/l, p < 0.001). Thyroid abnormalities detected by ultrasonography included hemiagenesis (0.5%), nodules (0.2%), cysts (0.7%), and hypoechogenicity (11.7%). Goiter was present in 1.9% of the children. Hypoechogenicity, a relevant marker of autoimmune thyroiditis, was the most common abnormality found in our study, and this may be linked to excessive iodine intake.

The prevalence of thyroid dysfunction in elderly cardiology patients with mild excessive iodine intake in the urban area of São Paulo.

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= <0.01) in patients, compared to the normal control group. No significant differences in serum TSH and free T4 values were observed when patients with atrial fibrillation (AF) where compared with those without arrhythmia. The median urinary iodine levels were 210 microg/L (40-856 microg/L), and iodine levels were higher in men than in women (p<0.01). Excessive iodine intake (urinary iodine >300 microg/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.

The prevalence of thyroid dysfunction in elderly cardiology patients with mild excessive iodine intake in the urban area of São Paulo

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 percent), whereas hypothyroidism (overt and subclinical) was found in 32 individuals (8.1 percent). Cysts were detected in 11 patients (2.8 percent), single nodules were detected in 102 (25.6 percent), and multinodular goiters were detected in 34 (8.5 percent). Hashimoto's thyroiditis was present in 16.8 percent patients, most of whom were women (83.6 percent). The serum TSH increased with age and was significantly higher (p= <0.01) in patients, compared to the normal control group. No significant differences in serum TSH and free T4 values were observed when patients with atrial fibrillation (AF) where compared with those without arrhythmia. The median urinary iodine levels were 210 µg/L (40-856 µg/L), and iodine levels were higher in men than in women (p<0.01). Excessive iodine intake (urinary iodine >300 µg/L) was observed in one-third of patients (30.8 percent). 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.

[Preoperative evaluation of cytologically indeterminate thyroid nodules with 18F-FDG PET]. / Avaliação pré-operatória com PET-18F-FDG de nódulos de tireóide com citologia indeterminada.

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.

Avaliação pré-operatória com PET-18F-FDG de nódulos de tireóide com citologia indeterminada / Preoperative evaluation of cytologically indeterminate thyroid nodules with 18F-FDG PET

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 por cento a 66 por cento, sendo de 39 por cento 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 percent. In our experience, the specificity was 39 percent. 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.

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.

Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil.

OBJECTIVE: To 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). Design This 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. METHODS: Thyroid 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. RESULTS: At 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 microg/l) and, in 14.1%, it was higher than 400 microg/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). CONCLUSIONS: Five 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.

[Usefulness of ultrasound in the diagnosis and management of well-differentiated thyroid carcinoma]. / Uso da ultra-sonografia no diagnóstico e seguimento do carcinoma bem diferenciado da tireóide.

Thyroid nodules are found in the vast majority of the population, but only 5 to 10% are malignant. Ultrasonography of the thyroid, by virtue of being a straightforward, non-invasive method presenting strong correlation with macroscopic aspects of the thyroid gland, is being increasingly used to identify nodules that present a higher risk of malignancy. The presence of certain ultrasonographic characteristics such as hypoechogenicity, microcalcifications, irregular contours and central vascularization on Doppler, increase the risk of the lesion being malignant. Conversely, nodules presenting benign ultrasonographic characteristics such as hyperechogenicity and a mixed sponge-like aspect, and a concordant cytology, have a negative predictive value of 96.6%. It is, thus, important to examine all nodular lesions and to identify suspicious lesions that need biopsy, especially in multinodular glands. Ultrasonography is also highly sensitive in the identification of suspicious cervical lymph nodes during the follow-up of patients with thyroid carcinoma, even when PCI is negative and serum thyroglobulin (Tg) levels are undetectable. Tg measurement in the needle wash-out content is recommended as this has proven to be more sensitive than cytology in the diagnosis of cervical metastasis, especially where there is liquid content, and it is not affected by the presence of anti-Tg antibodies.

Role of 18F-fluorodeoxyglucose positron emission tomography in preoperative assessment of cytologically indeterminate thyroid nodules.

OBJECTIVE: 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. METHODS: 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. 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. CONCLUSIONS: (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%.

Uso da ultra-sonografia no diagnóstico e seguimento do carcinoma bem diferenciado da tireóide / Usefulness of ultrasound in the diagnosis and management of well-differentiated thyroid carcinoma

Os nódulos tireóideos são encontrados em grande parte da população, mas somente 5 a 10 por cento 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 por cento. 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.

Thyroid nodules are found in the vast majority of the population, but only 5 to 10 percent are malignant. Ultrasonography of the thyroid, by virtue of being a straightforward, non-invasive method presenting strong correlation with macroscopic aspects of the thyroid gland, is being increasingly used to identify nodules that present a higher risk of malignancy. The presence of certain ultrasonographic characteristics such as hypoechogenicity, microcalcifications, irregular contours and central vascularization on Doppler, increase the risk of the lesion being malignant. Conversely, nodules presenting benign ultrasonographic characteristics such as hyperechogenicity and a mixed sponge-like aspect, and a concordant cytology, have a negative predictive value of 96.6 percent. It is, thus, important to examine all nodular lesions and to identify suspicious lesions that need biopsy, especially in multinodular glands. Ultrasonography is also highly sensitive in the identification of suspicious cervical lymph nodes during the follow-up of patients with thyroid carcinoma, even when PCI is negative and serum thyroglobulin (Tg) levels are undetectable. Tg measurement in the needle wash-out content is recommended as this has proven to be more sensitive than cytology in the diagnosis of cervical metastasis, especially where there is liquid content, and it is not affected by the presence of anti-Tg antibodies.

Preoperative assessment of thyroid nodules: role of ultrasonography and fine needle aspiration biopsy followed by cytology

PURPOSE:To evaluate the preoperative assessment of thyroid nodules using ultrasound studies and cytology of nodular aspirates. SUBJECTS AND METHODS: 2,468 patients with thyroid nodules were examined from 1999 to 2005. All patients were clinically examined and underwent ultrasonography followed by fine-needle aspiration biopsy (FNAB) and cytology. RESULTS:Nodules larger than 10 mm were classified ultrasonographically in a 4-tier system and received a score according to the criterion of possible malignancy. Cytological examinations were conducted independently by 2 cytologists and classified as benign (score 1), indeterminate (score 2), suspicious (score 3), and malignant (score 6). Combining both scores, an index was generated that would indicate a higher probability of malignancy (benign, doubtful, suspicious, and malignant). Thyroid surgery was performed in 274 patients. Of those, 115 patients had a score of 2 to 5 and only 8 had a histological diagnosis of thyroid cancer (6.9 percent). For patients with a score of 5 (n = 51), 11.5 percent had a malignant lesion, and 51 percent of the 61 patients with a score of 6 had confirmed thyroid cancer. Of the 98 patients with a combined score of 7 to 10, 99 percent had a histological confirmation of malignancy. CONCLUSIONS: The index score had a sensitivity of 94.1 percent and specificity of 77.5 percent. The overall accuracy was 85.8 percent. Therefore, we concluded that this methodology may improve the preoperative diagnosis of thyroid cancer in nodules larger than 10 mm. Association with other methods such as color Doppler echography, serum TSH concentration, galectin-3 expression analysis, and FDG/PET scan would be useful in avoiding the higher costs of thyroid surgical procedures.

OBJETIVO: Avaliar a possibilidade de diagnóstico pré-operativo de nódulos da tireóide (de diâmetro superior a 10mm) usando ultra-sonografia da glândula tireóide e citologia de punção aspirativa por agulha fina guiada pela ultra-sonografia. CASUíSTICA E MÉTODOS: Nódulos tireóideos (maiores que 10mm) foram classificados ultra-sonograficamente em graus de I a IV e escores numéricos de 1 a 4, de acordo com crescente possibilidade de malignidade. O exame citológico, subseqüentemente, classificou os nódulos como benigno (escore 1) indeterminado (escore 2) suspeito (escore 3) e maligno (escore 6). Somando-se os escores obtidos nas duas metodologias obtém-se um índice considerado benigno (índice combinado 2-4), duvidoso (índice combinado 5) suspeito para malignidade (índice combinado 6) e elevada probabilidade de malignidade (índice combinado 7 a 10). Cirurgia da Tireóide foi realizada em 274 pacientes, dos quais 64 apresentavam índice de 2-4; destes, apenas 2 pacientes (3,1 por cento) apresentaram comprovação histológica de câncer. Em pacientes com índice 5 (n= 51), 11,8 por cento apresentaram câncer de tireóide e, em 61 pacientes com índice 6, (n= 31), 51 por cento tiveram diagnóstico confirmado de malignidade. O índice combinado de 7-10 (n= 98) apresentou 99 por cento de pacientes com câncer de tireóide. CONCLUSÕES: O índice combinado apresentou sensibilidade de 94,1 por cento e especificidade de 77,5 por cento. A precisão desta metodologia foi de 85,8 por cento. Concluímos que o índice combinado pode ser útil no diagnóstico pré-cirúrgico do nódulo tireóideo, mormente se associado com outras metodologias como a ecografia com Doppler colorido, nível elevado de TSH sérico, análise de expressão de galectina-3 e imagens por FDG/PET.

Prevalence of chronic autoimmune thyroiditis in the urban area neighboring a petrochemical complex and a control area in Sao Paulo, Brazil.

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 microg Iodine/L in 58.5% of the total population. CONCLUSION: The high iodine intake (above 300 microg 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.

[Low-risk differentiated thyroid carcinoma--literature review and management guidelines]. / 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 greater 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.

Prevalence of chronic autoimmune thyroiditis in the urban area neighboring a petrochemical complex and a control area in Sao Paulo, Brazil

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.