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Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

This position statement was prepared to guide endocrinologists on the best approach to managing thyroid disorders during the coronavirus disease (COVID-19) pandemic. The most frequent thyroid hormonal findings in patients with COVID-19, particularly in individuals with severe disease, are similar to those present in the non-thyroidal illness syndrome and require no intervention. Subacute thyroiditis has also been reported during COVID-19 infection. Diagnosis and treatment of hypothyroidism during the COVID-19 pandemic may follow usual practice; however, should avoid frequent laboratory tests in patients with previous controlled disease. Well-controlled hypo and hyperthyroidism are not associated with an increased risk of COVID-19 infection or severity. Newly diagnosed hyperthyroidism during the pandemic should be preferably treated with antithyroid drugs (ATDs), bearing in mind the possibility of rare side effects with these medications, particularly agranulocytosis, which requires immediate intervention. Definitive treatment of hyperthyroidism (radioiodine therapy or surgery) may be considered in those cases that protective protocols can be followed to avoid COVID-19 contamination or once the pandemic is over. In patients with moderate Graves’ ophthalmopathy (GO) not at risk of visual loss, glucocorticoids at immunosuppressive doses should be avoided, while in those with severe GO without COVID-19 and at risk of vision loss, intravenous glucocorticoid is the therapeutic choice. Considering that most of the thyroid cancer cases are low risk and associated with an excellent prognosis, surgical procedures could and should be postponed safely during the pandemic period. Additionally, when indicated, radioiodine therapy could also be safely postponed as long as it is possible.

Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.

Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Introduction: Several studies have shown an increased risk of thyroid malignancies in patients with elevated TSH levels, even if these levels fell within the normal range. The aim of this study was to evaluate the relationship between TSH and risk of malignancy in patients with thyroid nodules. Material and methods: We included 622 patients with thyroid nodules evaluated by fine needle aspiration and/or thyroidectomy and diagnosed by cytology or histology. Clinical and laboratory data, such as gender, weight, ultrasound findings, serum TSH, and free T4, were obtained from medical records or collected during each patient's first visit to our centre, prior to any intervention. Results: Thyroid cancer was more prevalent in males (p = 0.012) and in patients with a solitary nodule (p < 0.01). Malignant tumours were predominantly solid, whereas benign tumours were solid or mixed (p = 0.053). The carcinoma risk in patients with thyroid nodules increased with increasing serum TSH concentration, with a significant elevation in patients with serum TSH levels above 1.64 mU/L (p < 0.001). This relationship persisted even when the subgroup of patients undergoing thyroidectomy was analysed separately. Patients with follicular lesions presented with significantly higher TSH levels compared to patients with benign cytology (p < 0.001). We also found correlation between elevated TSH and tumour size (p = 0.005). Conclusions: Our results suggest that in patients with nodular thyroid disease the carcinoma risk rose in parallel with serum TSH concentration, with significant increases evident in patients with serum TSH greater than 1.64 mU/L. (Endokrynol Pol 2015; 66 (6): 480–485)

Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in DIO2 (iodothyronine deiodinase 2), high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned and many attempts to improve levothyroxine therapy compliance and absorption have been made.

Objective: The objective of this study was to determine the prevalence of celiac disease (CD) in adults with autoimmune thyroid disease (ATD) from the endocrinology outpatient setting in a university hospital in Southern Brazil. Subjects and methods: From the years 2007 to 2011, 254 patients with ATD were enrolled consecutively, Grave’s disease was diagnosed in 143 (56.3%) and Hashimoto’s thyroiditis in 111 (43.7%) of them. All patients answered a questionnaire related to symptoms that could be associated with CD and serum samples to screen for IgA anti-endomysial (EmA-IgA) were collected. EmA-IgA-positive patients were offered upper gastrointestinal endoscopy and biopsy of duodenum. Results: A total of 254 patients were included; 222 (87.4%) female, mean age 45.4 ± 13.43 years (18 to 79 years). EmA-IgA was positive in seven patients (2.7%) and five done endoscopy with biopsy. Of these, three diagnosis of CD was confirmed (1.2%). All the three patients with CD had higher EmA-IgA titration, were female and had Hashimoto’s thyroiditis. Like other patients with ATD, CD patients had nonspecific gastrointestinal symptoms, such as heartburn and gastric distention. In our study, one in each 85 patients confirmed the diagnosis of CD. Conclusion: We found a prevalence of 1.2% (1:85) of confirmed CD among Brazilian patients with ATD. Although some IgA-EmA positive patients had Graves’ disease and one was male, all three patients with confirmed CD were female and had Hashimoto’s thyroiditis. Arq Bras Endocrinol Metab. 2014;58(6):625-9

Hypothyroidism is treated with oral levothyroxine. Some patients fail to attain adequate control because of poor compliance. Delaying breakfast to take levothyroxine on an empty stomach can decrease adherence to hypothyroidism treatment. The objective of this study was to evaluate whether administering levothyroxine with breakfast can maintain thyrotropin (TSH) levels in the therapeutic range, without major clinical changes.A prospective, randomized, open-label, crossover study was conducted to compare usual levothyroxine administration while in a fasting state with administration during breakfast. From September 2008 to April 2009, 45 patients with primary hypothyroidism who received levothyroxine were recruited. The patients completed 180 days of the protocol and were randomized to 90 days of each levothyroxine administration regimen (while fasting or with breakfast). Clinical and biochemical analyses were performed at baseline and on days 45, 90, 135, and 180. The primary outcome was TSH level.Forty-two patients completed the protocol. The TSH level was higher for levothyroxine administration with breakfast than while fasting (2.89 vs. 1.9 mIU/L, p=0.028). Uncontrolled hypothyroidism (TSH ≥3.5 mIU/L) occurred regardless of the type of levothyroxine administration (p=0.26). No risk factors were identified for TSH elevation.Levothyroxine administration with breakfast could be an alternative regimen for patients who have adherence difficulties due to the need for delaying intake, and is more likely to cause variability in the TSH level, meaning the patient should be followed more closely. For patients in whom a specific serum TSH goal is important, taking levothyroxine while fasting is recommended.

Exames laboratoriais são fundamentais para o diagnóstico acurado e o monitoramento custo-efetivo das disfunções tireoidianas. Quando há alta suspeita clínica, as dosagens hormonais apenas confirmam o diagnóstico. No entanto, na maioria dos pacientes, a sintomatologia é sutil e inespecífica, de forma que apenas testes bioquímicos podem detectar o transtorno. O objetivo deste artigo é fazer uma análise crítica do uso apropriado dos principais testes de função tireoidiana, entre eles a dosagem sérica do hormônio estimulante da tireoide (TSH), dos hormônios tireoidianos e dos anticorpos antitireoidianos. Mediante um levantamento na base de dados do MedLine, são discutidas as principais armadilhas e interferências relacionadas ao uso cotidiano desses testes e apresentadas recomendações para otimizar a utilização dessas ferramentas diagnósticas na prática clínica. Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.

This study aimed to verify the impact of levothyroxine replacement on health-related quality of life (HRQoL) in a Brazilian sample of primary hypothyroidism patients. A cross-sectional study was performed with 2,057 consecutive primary hypothyroidism patients on levothyroxine (LT4) replacement at four referral centers in Brazil (median age = 53; 25th percentile = 43; 75th percentile = 61 years). Patient biochemical data were acquired from medical records, and patients completed a questionnaire on socioeconomic issues and clinical signs and symptoms of hypothyroidism. HRQoL was assessed using the SF-36v2. Patients were divided into three groups according to TSH levels: overtreated (OvT; TSH0.4 mU/L), appropriately treated (AT; TSH between 0.4 and 4.0 mU/L), and undertreated (UnT; TSH4.0 mU/L). Patients were also analyzed by TSH and FT4 serum levels: overt hyperthyroidism (OHyper; TSH0.4 mU/L and FT41.9 ng/dL), subclinical hyperthyroidism (SHyper; TSH0.4 mU/L and FT4 0.8-1.9 ng/dL), subclinical hypothyroidism (SHypo; TSH4.0 mU/L and FT4 0.8-1.9 ng/dL), and overt hypothyroidism (OHypo; TSH4.0 mU/L and FT40.8 ng/dL). A total of 14.4 % of patients were OvT, with 13.0 % SHyper and 1.4 % OHyper. The prevalence of UnT was 25.9 %, with 21.5 % SHypo and 4.4 % OHypo. Overtreatment was not associated with HRQoL impairment. UnT patients had worse HRQoL than AT patients, especially for physical and emotional aspects, independent of SHypo or OHypo status. Hypothyroidism undertreatment is associated with poor patient HRQoL. Therefore, adequate LT4 therapy should be given to maintain serum TSH within the reference range.

Objective To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism. Subjects and methods This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16. Results Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged. Conclusions The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Graves' disease is commonly treated with curative intent using radioactive iodine (RAI). While higher doses have been shown to increase success rates, more evidence is needed. Further, very few studies assess the time to treatment success without the need for antithyroid drugs after a single dose of RAI within the first year post-dose, despite earlier success being an important treatment objective. We aimed to evaluate the outcome of different RAI doses in terms of success rates and time to achieve this success (eu- or hypothyroidism). We hypothesized that higher doses would not only increase success rates, but bring about successful treatment earlier.We retrospectively analyzed the medical records of all patients diagnosed with Graves' disease between 1994 and 2009. Details of RAI treatment and outcomes thereof were documented. In our analysis, we divided the patients who received RAI treatment into three groups according to the dose received: I (≤15 mCi); II (16-20 mCi); III (≥21 mCi).There were 498 patients diagnosed with Graves' disease. However, 105 were either lost to follow-up or still undergoing treatment. Of the remaining 393, there were 258 who received RAI treatment. The average initial dose was 21.42±6.5 mCi and overall success rate was 86%. Success rates were 74%, 85%, and 89% (p0.05), while average time to successful treatment was 8.1, 4.6, and 2.9 months, respectively (p0.001), for groups I, II, and III. When 20 mCi was given empirically, 85% obtained successful treatment; most of these within 3 months (mean 3.9; mode and median 3 months).This study provides additional evidence that success post-treatment correlates with administered dose and shows clearly, for the first time, that successful treatment is achieved earlier with higher doses. This knowledge is relevant to all clinicians managing Graves' disease as it can be taken into consideration when discussing treatment plans with patients.

Objective: Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative. Subjects and methods: This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4. After six weeks, they switched regimens. Thyroid parameters were measured at baseline, and after 42 and 84 days. Echocardiogram and hyperthyroidism symptoms were evaluated before and four hours after LT4 intake. Results: In the weekly dose treatment, fT4 levels were higher after taking LT4, and lower seven days after the last dose; by the 6th week there was a small decrease in T3 levels. TSH remained unchanged and there were no hyperthyroidism symptoms or echocardiographic manifestations. Conclusion: Weekly dose leads to transient increases in fT4, without hyperthyroidism or cardiac symptoms. That approach seems to be a safe alternative for the treatment of hypothyroidism. Arq Bras Endocrinol Metab. 2012;56(4):250-8

Recent literature advocates the decrease of the upper limit of the normal thyrotropin (TSH) reference range. The objective of this study was to determine whether treated hypothyroid patients maintained within a low-normal TSH range (0.4-2.0 mIU/L) have better clinical outcomes than those maintained within a high-normal TSH range (2.0-4.0 mIU/L).The study was performed in a thyroid outpatient clinic of a tertiary hospital. This was a prospective, interventional study. Forty-two participants with newly diagnosed overt primary hypothyroidism were paired in two groups: group 1 (n=20), low-normal target TSH; group 2 (n = 22), high-normal target TSH. Levothyroxine was initiated, and dose was adjusted to achieve and sustain the target TSH value during the study period. After the target TSH was reached, participants were evaluated every 3 months for thyroid function, serum lipid profile, resting energy expenditure (REE), body composition, and bone mineral density, for 12 months.Nineteen patients in group 1 and 16 in group 2 completed the study. In the whole-group analysis, total cholesterol (p = 0.01), low-density lipoprotein cholesterol (p = 0.004), and triglycerides (p0.001) decreased after treatment, whereas REE per kilogram of lean body mass (p = 0.001) and total fat body mass (p =0.02) increased. Group 1 patients had a significantly higher relative increase in REE (+7.1% ± 11.3% vs. +3.6% ± 15.1%, p = 0.02). There was no difference between the groups in the other variables.Despite recent trends toward lowering the upper limit of normal TSH range, the results of this 12-month study provided no substantial clinical evidence to corroborate that treatment of primary hypothyroidism should aim at maintaining TSH levels in a low-normal range

Thyroid nodules can be biopsied by fine needle aspiration (FNA) or fine needle capillary (FNC) biopsies. However, there is controversy on whether one technique is superior to another. In a randomized cytopathologist-blinded cross-sectional study, 260 patients (238 females, age 43.2 +/- 12.6) with nodular (82.7%) and diffuse goiter (17.3%) underwent 520 FNAs and 520 FNCs (not guided by ultrasound). Smears were scored for sample adequacy, and diagnosed as malignant, benign, suspicious, or nondiagnostic. Diagnostic accuracy was calculated based on the histological findings of 58 patients submitted to surgery. Intra-technique diagnostic accuracy and sample adequacy was seen in all samples. FNA and FNC provided similar cytological diagnosis, respectively (benign: 75.8% vs. 74.2%, p = 0.600; malignant: 3.8% vs. 3.8%, p = 0.871; suspicious: 10.4% vs. 10.8%, p = 0.913; and nondiagnostic: 10.0% vs. 11.2%, p = 0.598). Adequacy scores were similar by FNA (7.94 +/- 2.84) and FNC (7.96 +/- 2.81, p = 0.909). The same proportion of adequate or superior samples was seen in both techniques (91.6%). Sensitivity was equal to 85.7% for FNA and 100% for FNC. Similarly, specificity was 100% for both techniques. FNA and FNC provide the similar sample adequacy and diagnostic accuracy. The choice of technique should be based on the operator's personal preferences and experience.

A terapêutica com drogas antitireoidianas pode ser acompanhada de efeitos colaterais. Propiltiouracil (PTU) pode induzir vasculites anticorpo anti-citoplasma de neutrófilos (ANCA) positivas, na maioria das vezes relacionadas ao subtipo mieloperoxidase (ANCA-MPO). O nosso objetivo é relatar o caso de uma paciente com doença de Graves que desenvolveu auto-imunidade induzida por PTU, com manifestações cutâneas, pulmonares e renais, associadas à positividade do ANCA. O exame anátomo-patológico pulmonar revelou hemorragia difusa e a biópsia renal demonstrou glomeruloesclerose segmentar e focal. Foi tratada com pulsoterapia com corticóides e ciclofosfamida, com boa evolução clínica. Este caso enfatiza a necessidade de detecção e tratamento precoce deste efeito adverso relativamente raro do PTU.

Among the amiodarone-induced thyroid dysfunctions, thyrotoxicosis is the most troublesome and with the highest rate of morbidity and mortality. Treatment consists in the use of a high dose of anti-thyroid drugs and steroids in an isolated form or in combination. Association of several other drugs have been proposed for the treatment of refractory cases. In this study we report the case of a 40 y.o. patient, with a history of idiopatic dilated miocardiopathy, who developed severe amioradone-induced thyrotoxicosis after heart transplantation. Since the patient did not respond to an initial treatment consisting of a high dose of anti-thyroid drugs combined with steroids, a low dose of lithium carbonate was added for a short period of time, which resulted in normalization of the thyroid function. In this case, the addition of lithium carbonate to the two other drugs resulted in a successful and safety therapy in controlling amiodarone-induced thyrotoxicosis.

O carcinoma diferenciado de tireóide, papilífero ou folicular, usualmente tem um curso relativo benigno após a tireoidectomia total e ablação de remanescentes tireoideanos com 131I. Em contraste, o carcinoma anaplásico de tireóide ou carcinoma indiferenciado de tireóide, também derivado do epitélio folicular tireoideano, é uma das neoplasias humanas mais agressivas, que perdeu a maioria ou todas as características do tecido de origem. Crescimento tumoral rápido é um presságio de mortalidade precoce a menos que se institua tratamento combinado agressivo. Não dispomos ainda de um tratamento que leva à cura definitiva para a maioria dos pacientes. A melhor conduta se constitui de um tratamento cirúrgico agressivo associado com a combinação de novos agentes quimioterápicos e radioterapia externa. Well-differentiated thyroid carcinoma (TC), as papillary and follicular carcinoma, usually follows a relatively benign course after total thyroidectomy and thyroid remnant ablation with 131I. In contrast, anaplastic TC or undiferentiated TC, also derived from the thyroid follicular epithelium, refers to one of the more aggressive human malignancies, which have lost most or all characteristics of the tissue from which it originated. Rapid tumor growth presages early mortality unless combined therapy is aggressively pursued. Definitive curative approach does not exist for most patients. The best approach is still aggressive surgery combined with the associated use of new chemotherapies associated with local external beam radiotherapy.

Objective The objective of this study was to evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules. Subjects and methods We evaluated 120 patients with benign thyroid nodules. Patients underwent evaluation of serum TSH and free T4, cervical ultrasound, and thyroid scintigraphy (in those with suppressed TSH levels). The application of sterile ethanol 99% was guided by ultrasound, with the injected volume amounting to one-third of the nodule volume. Response was considered complete (reduction of 90%); partial (reduction between 50 and 90%); or none (reduction of < 50%). Autonomous nodules were evaluated for normalization of TSH levels. Results Among the nodules studied, 30.8% were solid, 56.7% were mixed, 12.5% were cystic, and 21.6% were hyperfunctioning. The initial volume of the treated nodules ranged from 0.9 to 74.8 mL (mean 13.1 ± 12.4 mL). We performed 1-8 sessions of PEI, applying an average of 6.2 mL of ethanol for patient. After 2 years of follow-up, 17% of patients achieved a complete response (94% reduction); 53%, a partial response (70% reduction); and 30%, no response. A reduction in the volume of autonomous nodules was noted in 70% of cases, and 54% had a normalized value of TSH. The main side effect is local pain, lasting less than 24 hours in most cases. Conclusion This study showed that PEI is a safe and effective procedure for treatment of benign, solid or mixed thyroid nodules. Most cases resulted in significant reduction in nodule volume, with normalization of thyroid function. Arq Bras Endocrinol Metab. 2014;58(9):912-7 Objetivo O objetivo deste estudo foi avaliar a eficácia e segurança da injeção percutânea de etanol (IPE) no tratamento de nódulos tireoidianos benignos. Sujeitos e métodos Foram avaliados 120 pacientes com nódulos benignos de tireoide. Todos realizaram dosagens de TSH, T4 livre, ecografia cervical (US) e cintilografia de tireoide (em pacientes com TSH suprimido). A aplicação de etanol estéril a 99% foi guiada por US e o volume de etanol injetado correspondeu a um terço do volume nodular calculado. A resposta foi considerada completa (redução de 90%); parcial (redução entre 50 e 90%) ou ausência de resposta (redução menor que 50%). Nos nódulos autônomos, foi avaliada a normalização do TSH. Resultados Entre os nódulos estudados, 30,8% eram sólidos, 56,7% eram mistos, 12,5% eram císticos e 21,6%, nódulos hiperfuncionantes. O volume inicial dos nódulos tratados variou de 0,9 a 74,8 mL (média 13,1 ± 12,4 mL). Foram realizadas de 1 a 8 sessões de IPE (média 2,8), com aplicação média de 6,2 mL de etanol por paciente. Após dois anos de seguimento, 17% dos pacientes obtiveram resposta completa (redução de 94%), 53% obtiveram resposta parcial (redução de 70%) e 30% não responderam. Houve redução de volume nos nódulos autônomos em 70% dos casos, e 54% normalizaram o valor do TSH. Os efeitos colaterais registrados foram decorrentes apenas do desconforto no local de aplicação. Conclusão Este trabalho mostrou que a IPE é um procedimento seguro e eficaz para tratamento de nódulos benignos, sólidos ou mistos de tireoide. Na maioria dos casos, ocasiona redução do volume nodular, com melhora dos sintomas compressivos e normalização da função tireoidiana. Arq Bras Endocrinol Metab. 2014;58(9):912-7

Nódulos tireoidianos são muito frequentes, sobretudo quando se empregam métodos sensíveis de imagem. Embora o câncer seja proporcionalmente raro, sua incidência vem aumentando, especialmente de tumores pequenos, cuja evolução clínica é incerta. A maioria dos pacientes com carcinoma diferenciado de tireoide evolui bem quando adequadamente tratada, com índices de mortalidade similares à população geral. Por outro lado, um percentual não desprezível apresenta recidivas e alguns eventualmente não respondem às terapias convencionais, evoluindo para óbito. Assim, o desafio é distinguir os pacientes merecedores de condutas mais agressivas e, ao mesmo tempo e não menos importante, poupar a maioria de tratamentos e procedimentos desnecessários. Atualizamos o Consenso Brasileiro publicado em 2007, ressaltando os avanços diagnósticos e terapêuticos que os participantes, de diferentes Centros Universitários do Brasil, consideram mais relevantes para prática clínica. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão da literatura pertinente. Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature. Instituto de Ensino e Pesquisa Serviço de Endocrinologia Universidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Clínica Médica Universidade Federal do Paraná Serviço de Endocrinologia e Metabologia Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica Médica Universidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto Alegre Serviço de Endocrinologia Universidade Federal do Rio de Janeiro Faculdade de Medicina Hospital Universitário Clementino Fraga Filho UNIFESP, EPM, Depto. de Medicina SciELO

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:04:35Z No. of bitstreams: 1 S0004-27302013000300006.pdf: 228940 bytes, checksum: e00ee3bcdf0c90f9ee85aefe477034ac (MD5) Made available in DSpace on 2013-08-22T19:04:35Z (GMT). No. of bitstreams: 1 S0004-27302013000300006.pdf: 228940 bytes, checksum: e00ee3bcdf0c90f9ee85aefe477034ac (MD5) Previous issue date: 2013-04-01 Made available in DSpace on 2013-09-30T20:07:36Z (GMT). No. of bitstreams: 2 S0004-27302013000300006.pdf: 228940 bytes, checksum: e00ee3bcdf0c90f9ee85aefe477034ac (MD5) S0004-27302013000300006.pdf.txt: 141453 bytes, checksum: 62758c72c30112a5ded8c5728c33e80e (MD5) Previous issue date: 2013-04-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:17:17Z No. of bitstreams: 2 S0004-27302013000300006.pdf: 228940 bytes, checksum: e00ee3bcdf0c90f9ee85aefe477034ac (MD5) S0004-27302013000300006.pdf.txt: 141453 bytes, checksum: 62758c72c30112a5ded8c5728c33e80e (MD5) Made available in DSpace on 2014-05-20T15:17:17Z (GMT). No. of bitstreams: 2 S0004-27302013000300006.pdf: 228940 bytes, checksum: e00ee3bcdf0c90f9ee85aefe477034ac (MD5) S0004-27302013000300006.pdf.txt: 141453 bytes, checksum: 62758c72c30112a5ded8c5728c33e80e (MD5) Previous issue date: 2013-04-01 INTRODUÇÃO: O hipertireoidismo é caracterizado pelo aumento da síntese e liberação dos hormônios tireoidianos pela glândula tireoide. A tireotoxicose refere-se à síndrome clínica decorrente do excesso de hormônios tireoidianos circulantes, secundário ao hipertireoidismo ou não. Este artigo descreve diretrizes baseadas em evidências clínicas para o manejo da tireotoxicose. OBJETIVO: O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o manejo, diagnóstico e tratamento dos pacientes com tireotoxicose, de acordo com as evidências mais recentes da literatura e adequadas para a realidade clínica do país. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. RESULTADOS: Foram definidas 13 questões sobre a abordagem clínica inicial visando ao diagnóstico e ao tratamento que resultaram em 53 recomendações, incluindo investigação etiológica, tratamento com drogas antitireoidianas, iodo radioativo e cirurgia. Foram abordados ainda o hipertireoidismo em crianças, adolescentes ou pacientes grávidas e o manejo do hipertireoidismo em pacientes com oftalmopatia de Graves e com outras causas diversas de tireotoxicose. CONCLUSÕES: O diagnóstico clínico do hipertireoidismo, geralmente, não oferece dificuldade e a confirmação diagnóstica deverá ser feita com as dosagens das concentrações séricas de TSH e hormônios tireoidianos. O tratamento pode ser realizado com drogas antitireoidianas, administração de radioiodoterapia ou cirurgia de acordo com a etiologia da tireotoxicose, as características clínicas, disponibilidade local de métodos e preferências do médico-assistente e paciente. INTRODUCTION: Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. OBJECTIVE: This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. MATERIALS and METHODS: After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. RESULTS: We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. CONCLUSIONS: The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient. Universidade Federal do Rio Grande do Sul (UFRGS) Hospital de Clínicas de Porto Alegre Serviço de Endocrinologia Universidade Federal de Ciências da Saúde de Porto Alegre Departamento de Medicina Interna Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica Universidade Federal de Uberlândia (UFU) Hospital de Clínicas Serviço de Endocrinologia e Metabologia Universidade Federal do Rio de Janeiro (UFRJ) Serviço de Endocrinologia Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica Médica Universidade Federal da Bahia (UFBA) Instituto de Ciências da Saúde Departamento de Biorregulação Universidade Estadual de Campinas Faculdade de Ciências Médicas Associação Médica Brasileira Conselho Federal de Medicina Universidade Estadual Paulista Faculdade de Medicina de Botucatu Departamento de Clínica Médica

Na avaliação da função tireoideana utiliza-se como método diagnóstico as medidas de TSH, T4 e T3 totais e livres. Entretanto, em alguns casos ocorre a ligação não específica com reagentes dos ensaios que vão, desta forma, interferir com as medidas destes hormônios. Estas interferências irão resultar em concentrações séricas anormais de hormônios tireoideanos, não consistentes com a avaliação clínica e demais exames laboratoriais destes pacientes. Auto-anticorpos anti-hormônio tireoideano são a classe de fatores que mais frequentemente interferem com vários ensaios. Relatamos o caso de uma paciente de 62 anos, com queixas de ansiedade e palpitações e exame físico normal. Na avaliação laboratorial detectamos níveis séricos persistentemente elevados de T3 total, com níveis séricos normais de TSH e T4 total. A presença de anticorpos anti-T3 foi confirmada por radioimunoprecipitação. Resultados que parecem ser inconsistentes ou incompatíveis com os demais exames laboratoriais, na presença ou não de sintomais em geral inespecíficos, devem levantar a suspeita da presença de fatores interferentes no ensaio. Desta forma, evita-se o diagnóstico errôneo de disfunção tireoideana e, consequentemente, um tratamento desnecessário e até mesmo deletério.

Several studies with ambiguous results have examined the effects of selective serotonin reuptake inhibitors (SSRIs) on thyroid function. This study aimed to establish the effects of fluoxetine and sertraline treatments on thyroid function and thyroid autoimmunity in patients with major depression and primary hypothyroidism and in patients with major depression and normal thyroid function.This was a prospective, controlled, intervention study involving 67 subjects: 28 patients with major depression and hypothyroidism on adequate levothyroxine therapy randomized for treatment with fluoxetine (n = 13) or sertraline (n = 15); 29 patients with major depression and normal thyroid function treated with fluoxetine (n = 15) or sertraline (n = 14) and 10 control patients with hypothyroidism on adequate levothyroxine therapy without depression. Main outcome measures included thyrotropin, thyroxine (T(4)), free thyroxine, triiodothyronine (T(3)), anti-thyroid peroxidase antibodies, and Hamilton depression (HAM-D) rating scale.Patients with normal thyroid function who were treated with fluoxetine demonstrated a significant reduction of T(3) after 15 and 30 days of treatment (p = 0.034 and p = 0.011) and a significant reduction of T(4) throughout the intervention period (p = 0.04 after 15 days; p = 0.015 after 30 days; and p = 0.029 after 90 days). However, all thyroid parameters remained within the euthyroid range. No changes were observed among hypothyroid patients on levothyroxine replacement therapy who were treated with either SSRI. The degree of improvement in depression symptoms (HAM-D rating scale) after 90 days of SSRI treatment was correlated with T(3) levels reduction among patients with normal thyroid function randomized for sertraline and among patients with hypothyroidism randomized for fluoxetine. T(3) levels remained within the euthyroid range during the study period.Neither fluoxetine nor sertraline was associated with clinically significant changes in thyroid function or thyroid autoimmunity in either primary hypothyroid or normal thyroid function patients with depression. However, results suggest that patients with normal thyroid function who were treated with fluoxetine are more susceptible to minor changes within the serotoninergic system than patients with hypothyroidism on the same SSRI therapy. To the best of our knowledge, this is the first study to demonstrate the safety of administering SSRIs in hypothyroid patients.

Os nódulos tireoidianos constituem a principal manifestação clínica de uma série de doenças da tireóide com uma prevalência de aproximadamente 10% na população adulta. O maior desafio é excluir o câncer da tireóide, que ocorre em 5 a 10% dos casos. Os carcinomas diferenciados respondem por 90% dos casos de todas as neoplasias malignas da tireóide. A maioria dos pacientes com carcinoma diferenciado apresenta, geralmente, um bom prognóstico quando tratada adequadamente, com índices de mortalidade similares à população geral. No entanto, alguns indivíduos apresentam doença agressiva, desafiando o conhecimento atual e ilustrando a complexidade do manejo dessa neoplasia. No presente trabalho, reunimos 8 membros do Departamento de Tireóide da Sociedade Brasileira de Endocrinologia & Metabologia, para elaborarmos, por consenso, as diretrizes brasileiras no manejo dos nódulos tireoidianos e do câncer diferenciado da tireóide. Os membros participantes representam diferentes Centros Universitários do Brasil, refletindo diferentes abordagens diagnósticas e terapêuticas. Inicialmente, cada participante ficou responsável pela redação de determinado tema a ser enviado ao Coordenador, que, após revisão editorial e elaboração da primeira versão do manuscrito, enviou ao grupo para sugestões e aperfeiçoamentos. Quando concluído, o manuscrito foi novamente enviado e revisado por todos. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão pertinente da literatura. Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

A 26-year-old pregnant woman presenting with repeated episodes of vaginal bleeding, weight loss, and shortness of breath was diagnosed with choriocarcinoma with metastases to both lungs. Chorionic gonadotropin levels (hCG) were >2.5 x 10(6)mU/mL. Consistent with hCG-induced subclinical hyperthyroidism, she had a suppressed TSH of 0.037mU/L (0.49 - 4.67), a T4 of 18.1µg/dL (4.9 - 10.7), and T3 of 136ng/dL (45 - 137). Chemotherapy with a combined regimen with etoposide, methotrexate, and dactinomycine was started. The initial course was complicated by urosepsis with respiratory distress requiring endotracheal intubation for 3 days. She then improved rapidly, and her thyroid function tests were within normal limits by day 12. Six months later, after ten cycles of chemotherapy, the patient was in remission without signs of residual tumor or hCG-induced paraneoplastic activity. Relatamos o caso de uma gestante de 26 anos apresentando episódios de sangramento vaginal, perda ponderal e dispnéia, que recebeu o diagnóstico de coriocarcinoma com metástases pulmonares. O nível de gonadotrofina coriônica (hCG) era >2,5 x 10(6)mU/mL. O TSH era de 0,037mU/L (0,49 - 4,67), o T4 de 18,1ug/dL (4,9 - 10,7), e o T3 de 136ng/dL (45 - 137), confirmando o quadro de hipertireoidismo subclínico induzido pela hCG. A paciente foi submetida a um regime combinado de quimioterapia com etoposídeo, metotrexate e dactiomicina. A evolução inicial foi complicada por um quadro de urosepsis com insuficiência respiratória, necessitando entubação endotraqueal por 3 dias. Após, houve melhora progressiva com normalização dos testes de função tireoideana no 12º dia de internamento. Após 6 meses e 10 ciclos de quimioterapia, a paciente estava em remissão e sem sinais de tumor residual ou de atividade paraneoplásica dependente de hCG.