Diagnostic Utility of Procalcitonin for Sporadic Medullary Thyroid Carcinoma in Patients with Nodular Disease and Mild or Moderate Hypercalcitoninemia.

Many authors recommend the measurement of serum calcitonin (Ctn) to screen for sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules. In this situation, procalcitonin (pro-Ctn) would have greater utility in patients with hypercalcitoninemia<100 pg/ml. The aim of this study was to evaluate the utility of pro-Ctn in patients with thyroid nodules and without a suspicion of familial MTC or type 2 multiple endocrine neoplasia who had mild or moderate hypercalcitoninemia without an apparent cause. Consecutive patients with nodular thyroid disease assessed routinely by Ctn measurement were selected. Sixty patients with basal Ctn>10 pg/ml but<100 pg/ml were included. Nine patients (15%) had MTC, with cytology being diagnostic in only four. Among the 51 patients without MTC, pro-Ctn was<0.1 ng/ml in 46 (90.2%). All patients with MTC had pro-Ctn>0.1 ng/ml. Basal Ctn was>24.6 pg/ml in all patients with MTC and in 42 patients (82.3%) without MTC. It is noteworthy that among patients with basal Ctn>24.6 pg/ml (n=18) pro-Ctn>0.1 ng/ml identified all patients with MTC and 64.2% of subjects with these pro-Ctn concentrations had this tumor. In conclusion, we did not find superiority of pro-Ctn over Ctn for the diagnosis of sporadic MTC in patients with nodular disease and mild or moderate hypercalcitoninemia. However, in the case of patients with hypercalcitoninemia in the gray zone, pro-Ctn has an excellent negative predictive value while the data regarding its positive predictive value are not uniform.

Natural history, predictive factors of apparent disease (structural or biochemical) and spontaneous excellent response in patients with papillary thyroid carcinoma and indeterminate response to initial therapy with radioiodine.

BACKGROUND: About 20% of patients with papillary thyroid carcinoma (PTC) submitted to total thyroidectomy followed by radioactive iodine (RAI) exhibit an indeterminate response to therapy. The aim was to evaluate the natural history, predictive factors of apparent disease (structural or biochemical), and spontaneous excellent response in patients with PTC and an initial indeterminate response to RAI therapy defined based on unstimulated Tg (u-Tg). METHODS: We evaluated 164 patients who were initially treated with total thyroidectomy and RAI and who had an indeterminate response to therapy (u-Tg between 0.2 and 1 ng/ml, undetectable anti-Tg antibodies [TgAb], and neck ultrasonography [US] without anomalies). None of the patients received empirical therapy with RAI. The patients were followed up for 24 to 144 months (median 72 months). RESULTS: Apparent disease occurred in 16 patients (9.7%), including 13 with structural disease and 3 with u-Tg elevation > 1 ng/ml, but no tumor was detected by the imaging methods (biochemical disease). A higher frequency of disease was observed in patients with >3 lymph node metastases (LNM) and initial u-Tg >0.35 ng/ml. The frequency was only 2% among patients with ≤3 LNM and u-Tg ≤0.35 ng/ml and 9.7% among patients with > 3 LNM or u-Tg >0.35 ng/ml, while the frequency was 27% in patients with >3 LNM and u-Tg >0.35 ng/ml. In the absence of any additional therapy, u-Tg was <0.2 ng/ml (excellent response) in the last assessment in 70 patients (42.7%). Only initial u-Tg was associated with a higher probability of spontaneously achieving an excellent response: 40/72 patients (55.5%) with u-Tg ≤0.35 ng/ml versus 30/92 patients (32.6%) with u-Tg >0.35 ng/ml. CONCLUSIONS: A minority of patients with PTC and an initial indeterminate response to RAI defined based on u-Tg develop apparent disease (structural or biochemical) and many spontaneously achieve an excellent response. The risk of disease can be refined based on parameters such as the extent of lymph node involvement and initial Tg concentration.

Development and validation of an instrument (CSII - Brazil) to assess users' conceptual and procedural knowledge of continuous subcutaneous infusion systems

ABSTRACT Objective: To develop, adapt and validate an instrument named "CSII - Brazil" to assess users' conceptual and procedural knowledge of continuous subcutaneous insulin infusion systems. Materials and methods: Methodological and exploratory study developed in three stages: a) instrument development; b) content validation and cultural adaptation (evaluation by a committee of experts and pre-test with CSII users); c) psychometric validation through instrument application in a sample of 60 patients by means of the web tool e-Surv. Internal consistency and reproducibility analyses were performed within IBM SPSS Statistics 20 programming environment. Results: The 16 multiple-choice question instrument successfully attained a content validity index of 0.97, showing satisfactory internal consistency, with 0.61 Cronbach's alpha [95% CI 0.462-0.746] and an intraclass correlation coefficient of 0.869 [95% CI: 0.789-0.919] between the test and retest scores. Conclusion: The CSII - Brazil instrument is considered adequate and validated to assess continuous subcutaneous infusion system users' conceptual and procedural knowledge.

Usefulness of accessible imaging methods in thyroid nodules with indeterminate cytology.

In thyroid nodules (TN) submitted to fine-needle aspiration (FNA), Bethesda categories III and IV are considered 'indeterminate' cytology. This result corresponds to 10-25% of all FNAs and the risk of malignancy (RoM) ranges from 10% to 30% for category III and from 15% to 40% for category IV. This review analyzed the practical applicability of accessible imaging method in the management of patients with cytologically indeterminate TN > 1 cm (ITN). When ITN are highly suspicious on ultrasonography (US), the RoM supports surgical indication even in the absence of additional tests. The same can be applied to ITN of intermediate suspicion but with elevated stiffness on elastography. Follow-up without additional tests is acceptable in the case of ITN with low-risk cytology and low-suspicion appearance on US and elastography (if obtained). In the case of ITN without highly suspicious US appearance, 123I scintigraphy may be obtained in patients with TSH < 1-1.5 mIU/L to rule out hyperfunctioning nodules before requesting diagnostic methods that are more expensive and less accessible. In addition, in ITN with not very suspicious US appearance, 18FDG-PET may be obtained. If this method does not reveal nodular uptake, the risk of the nodule corresponding to a macrocarcinoma is sufficiently low in order to allow follow-up. The positive predictive value of focal nodular uptake on 18FDG-PET depends on the pre-test RoM, cytological findings, and maximum SUV. There is currently no evidence for the use of CT, MRI or imaging using 99mTc-MIBI to define the nature of ITN.

Development and validation of an instrument (CSII - Brazil) to assess users' conceptual and procedural knowledge of continuous subcutaneous infusion systems.

OBJECTIVE: To develop, adapt and validate an instrument named "CSII - Brazil" to assess users' conceptual and procedural knowledge of continuous subcutaneous insulin infusion systems. METHODS: Methodological and exploratory study developed in three stages: a) instrument development; b) content validation and cultural adaptation (evaluation by a committee of experts and pre-test with CSII users); c) psychometric validation through instrument application in a sample of 60 patients by means of the web tool e-Surv. Internal consistency and reproducibility analyses were performed within IBM SPSS Statistics 20 programming environment. RESULTS: The 16 multiple-choice question instrument successfully attained a content validity index of 0.97, showing satisfactory internal consistency, with 0.61 Cronbach's alpha [95% CI 0.462-0.746] and an intraclass correlation coefficient of 0.869 [95% CI: 0.789-0.919] between the test and retest scores. CONCLUSION: The CSII - Brazil instrument is considered adequate and validated to assess continuous subcutaneous infusion system users' conceptual and procedural knowledge.

Can patients with papillary thyroid carcinoma and low postoperative thyroglobulin in the presence of clinically apparent lymph node metastases (cN1) be spared from radioiodine?

BACKGROUND: The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131I. METHODS: This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1-2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131I. RESULTS: The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor. CONCLUSIONS: The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.

Usefulness of Serum Calcitonin in Patients with Thyroid Nodules ≤ 1 cm Without an Indication for Fine-Needle Aspiration.

Fine-needle aspiration (FNA) is not necessary in adults with nodules ≤ 1 cm without apparent extrathyroidal extension (ETE) or lymph node (LN) involvement on ultrasonography (US). In the absence of FNA and serum calcitonin (Ctn) measurement, medullary thyroid microcarcinomas (microMTC) are not diagnosed. The aim of this prospective study was to evaluate Ctn levels in adults with a low clinical risk of MTC and nodules ≤ 1 cm without ETE or LN involvement on US. A total of 506 consecutively seen adults who had nodules with two or more suspicious features were included. Patients with elevated basal Ctn underwent a calcium stimulation test and FNA. Basal Ctn was normal in 490 patients (96.8%). In the 16 patients with elevated basal Ctn, FNA revealed MTC in only one patient and MTC was not suspected in the 15 patients with elevated basal Ctn. Three patients with stimulated Ctn<100 pg/ml and benign cytology were not submitted to surgery. MTC was excluded by histology in three patients with stimulated Ctn<100 pg/ml and indeterminate or suspicious cytology and in eight patients with stimulated Ctn>100 pg/ml. One patient with stimulated Ctn>100 pg/ml had MTC. Ctn was undetectable 6 months after surgery in two patients with MTC. Although uncommon, even subjects without a suspicious history and with nodules ≤ 1 cm without ETE or LN involvement on US, but with suspicious findings, can have microMTC. The measurement of Ctn permits the diagnosis of these cases.

Active Surveillance in Adults with Low-Risk Papillary Thyroid Microcarcinomas: A Prospective Study.

The acceptance and results of active surveillance in patients with low-risk papillary thyroid microcarcinomas (PTMC) are unknown in populations other than the Japanese population. This was the objective of the present prospective study. We selected patients ≥20 years who had thyroid nodules ≤1.2 cm with intermediate or high suspicion for malignancy on ultrasonography (US), not located near the recurrent laryngeal nerve and without extrathyroidal invasion or apparent lymph node metastases, whose cytology was suspicious (Bethesda V) or diagnostic (Bethesda VI) of papillary thyroid carcinoma. Patients who opted for active surveillance were followed up by biannual US. Fifteen patients (18.7%) readily opted for surgery and 12 (15%) for active surveillance. Fifty-three patients (66.2%) delegated the decision or wished to know the doctor's preference before deciding. After the doctor had declared his/her preference for active surveillance, 50 patients decided to have this management and three to have surgery. Only 1/70 patients exhibited tumor progression (growth associated with a suspicion of extrathyroidal invasion) after 30 months of follow-up. Two patients decided to have surgery during follow-up, although the indication was not defined by the study. A>50% reduction in tumor volume was observed in three patients. The study shows that active surveillance can be well accepted if doctors were convinced that it is the best option for patients with low-risk PTMC. At least the short-term results reproduced those observed in other populations, with tumor progression being uncommon.

Definition of the Response to Initial Therapy with Radioiodine in Patients with Differentiated Thyroid Carcinoma: Basal or Stimulated Thyroglobulin?

Basal thyroglobulin (b-Tg) measured with second-generation assay or stimulated Tg (s-Tg) can be used to define the response to therapy of differentiated thyroid carcinoma. However, they do not always define the same category and guidelines do not establish "if" or "when" s-Tg needs to be obtained. We studied 304 patients without clinically apparent disease or disease detected by neck ultrasonography and without anti-Tg antibodies 9-12 months after therapy. Based on b-Tg, 196 patients had an excellent response and 108 had an indeterminate response. Based on s-Tg, a change in category occurred in 10.2% of the patients with an initial excellent response (all to indeterminate response) and in half the patients with an initial indeterminate response (44.4% to excellent response and 5.5% to biochemical incomplete response). One case of recurrence was observed among patients with an initial excellent response but whose response changed to indeterminate after s-Tg, while no disease was detected among those who remained in the initial category; however, this difference was not significant. In patients with an initial indeterminate response, no recurrence was detected among those whose response changed to excellent after s-Tg, while 11.1 and 33.3% of those who remained in the initial category or whose response changed to biochemical incomplete, respectively, had structural disease. This study suggest that, in low- or intermediate-risk patients, s-Tg better defines the response to therapy with 131I when it is classified as indeterminate based on b-Tg using second-generation assay. However, s-Tg is not necessary when b-Tg defines the response as excellent.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion

ABSTRACT The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion.

The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a review for clinicians.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an encapsulated or clearly delimited, noninvasive neoplasm with a follicular growth pattern and nuclear features of papillary thyroid carcinoma (PTC). It is considered a 'pre-malignant' lesion of the RAS-like group. Ultrasonography (US), cytology and molecular tests are useful to suspect thyroid nodules that correspond to NIFTP but there is wide overlap of the results with the encapsulated follicular variant of PTC (E-FVPTC). In these nodules that possibly or likely correspond to NIFTP, if surgery is indicated, lobectomy is favored over total thyroidectomy. The diagnosis of NIFTP is made after complete resection of the lesion by observing well-defined criteria. In the case of patients who received the diagnosis of FVPTC and whose pathology report does not show findings of malignancy (lymph node metastasis, extrathyroidal invasion, vascular/capsular invasion), if the tumor was encapsulated or well delimited, the slides can be revised by an experienced pathologist to determine whether the diagnostic criteria of NIFTP are met, but special attention must be paid to the adequate representativeness of the capsule and tumor. Since NIFTP is not 'malignant', tumor staging is not necessary and patients are not submitted to thyroid cancer protocols or guidelines. We believe that patients with NIFTP without associated malignancy and without nodules detected by US of the remnant lobe (if submitted to lobectomy) can be managed like those with follicular adenoma.

Repeat Ultrasonography in the First Years after Therapy with Radioiodine Is Not Necessary in Most Patients with Papillary Thyroid Carcinoma when Postoperative Ultrasonography Is Negative: A Reduction of Costs and False-Positives.

BACKGROUND: Periodic ultrasonography (US) examination is recommended in many patients with papillary thyroid carcinoma (PTC) after treatment with radioactive iodine (RAI), but recurrences are confirmed in few cases. This study determined whether the indication of US in the first years after treatment with RAI can be selective when postoperative US and posttherapy whole-body scanning (RxWBS) ruled out persistent neck disease. METHODS: This was a prospective study. Two hundred and fifty-four patients with PTC (242 of intermediate risk) undergoing thyroidectomy and RAI, who had no apparent disease at the time of initial therapy (including negative postoperative US and RxWBS), were studied. The patients were followed up for 5 years after treatment with RAI by annual US. RESULTS: At the end of 5 years, 47 patients (18.5%) had at least one suspicious US, but neck recurrence was confirmed in only 4 patients (1.5% of all patients and 8.5% of those with suspicious US). The remaining cases were considered false-positives. US did not reveal disease in the first or second year after treatment with RAI in any patient. In the third, fourth, and fifth year after treatment with RAI, considering only patients with unstimulated Tg < 1 ng/mL in these assessments, US revealed disease in 0, 1 (0.4%), and 1 (0.4%) patient, respectively. CONCLUSION: The results suggest that low- or intermediate-risk patients with PTC without persistent disease after thyroidectomy (including negative postoperative US and RxWBS) do not require repeat US examination in the first two years after treatment with RAI. In the following years until the fifth year, US can be restricted to patients with Tg ≥1 ng/mL.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study.

INTRODUCTION: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. OBJECTIVE: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. METHODS: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n=36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n=33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n=13). RESULTS: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. CONCLUSION: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Are Papillary Thyroid Carcinomas That Are Candidates for Active Surveillance in Fact Classical Microcarcinomas Restricted to the Gland?

BACKGROUND: Patients with small papillary thyroid carcinomas (PTC) can currently be maintained under active surveillance (AS). The recommended criteria are the following: adult individual, tumor ≤1 cm and not adjacent to the trachea or recurrent laryngeal nerve, cytology non-suggestive of the aggressive subtype, absence of lymph node (LN) involvement and extrathyroidal extension (ETE) on ultrasonography (US), and absence of clinical distant metastases. This study aimed to evaluate the frequency of the following peri- and postoperative findings in patients who met the criteria for PTC being candidate for AS: tumor > 1 cm, aggressive subtype or vascular invasion, ETE, clinical LN metastases (cN1), and distant metastases. METHODS: We reviewed the results of peri- and postoperative evaluation and histology of patients with a preoperative diagnosis of PTC who would currently be candidates for AS. RESULTS: There were 124 patients (102 women) with nodules ≤1 cm (range 4-10 mm). All nodules corresponded to papillary microcarcinomas on histology and none of them were > 1 cm. Only one microcarcinoma (0.8%) was of the tall-cell subtype. Vascular invasion was found in 10 microcarcinomas (8%). None of the microcarcinomas were staged as T3b or T4, although microscopic ETE was observed in 25 tumors (20%). In 8 patients (6.4%), central LN involvement was suspected during perioperative evaluation and was confirmed by histology (cN1a). None of the patients had distant metastases (M0). CONCLUSION: Findings that define an intermediate risk of recurrence and favor total thyroidectomy were observed in 31.5% of patients with PTC who are candidates for AS.

Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy / Influência da tireoidite linfocítica crônica sobre o risco de doença persistente e recorrente em pacientes com carcinoma papilífero de tireoide e anticorpos antitireoglobulina elevados após a terapia inicial

Abstract Introduction In patients with papillary thyroid carcinoma who have negative serum thyroglobulin after initial therapy, the risk of structural disease is higher among those with elevated antithyroglobulin antibodies compared to patients without antithyroglobulin antibodies. Other studies suggest that the presence of chronic lymphocytic thyroiditis is associated with a lower risk of persistence/recurrence of papillary thyroid carcinoma. Objective This prospective study evaluated the influence of chronic lymphocytic thyroiditis on the risk of persistence and recurrence of papillary thyroid carcinoma in patients with negative thyroglobulin but elevated antithyroglobulin antibodies after initial therapy. Methods This was a prospective study. Patients with clinical examination showing no anomalies, basal Tg < 1 ng/mL, and elevated antithyroglobulin antibodies 8-12 months after ablation were selected. The patients were divided into two groups: Group A, with chronic lymphocytic thyroiditis on histology; Group B, without histological chronic lymphocytic thyroiditis. Results The time of follow-up ranged from 60 to 140 months. Persistent disease was detected in 3 patients of Group A (6.6%) and in 6 of Group B (8.8%) (p = 1.0). During follow-up, recurrences were diagnosed in 2 patients of Group A (4.7%) and in 5 of Group B (8%) (p = 0.7). Considering both persistent and recurrent disease, structural disease was detected in 5 patients of Group A (11.1%) and in 11 of Group B (16.1%) (p = 0.58). There was no case of death related to the disease. Conclusion Our results do not support the hypothesis that chronic lymphocytic thyroiditis is associated with a lower risk of persistent or recurrent disease, at least in patients with persistently elevated antithyroglobulin antibodies after initial therapy for papillary thyroid carcinoma.

Resumo Introdução Em pacientes com carcinoma papilífero de tireoide e com tireoglobulina sérica negativa após a terapia inicial, o risco de doença estrutural é maior entre aqueles com anticorpos antitireoglobulina elevados em comparação com pacientes sem anticorpos antitireoglobulina. Outros estudos sugerem que a presença de tireoidite linfocítica crônica está associada a um menor risco de persistência/recorrência do carcinoma papilífero de teireoide. Objetivo Este estudo prospectivo avaliou a influência da tireoidite linfocítica crônica sobre o risco de persistência e recorrência do carcinoma papilífero de tireoide em pacientes com tireoglobulina negativa, mas com anticorpos antitireoglobulinas elevados após a terapia inicial. Método Esse foi um estudo prospectivo, no qual foram selecionados pacientes com exame clínico sem anomalias; tireoglobulina basal < 1 ng/mL e anticorpos antitireoglobulina elevados 8-12 meses após ablação. Os pacientes foram divididos em dois grupos: Grupo A, com tireoidite linfocítica crônica no exame histológico; Grupo B, histologicamente sem tireoidite linfocítica crônica. Resultados O tempo de seguimento variou de 60 a 140 meses. Doença persistente foi detectada em 3 pacientes do Grupo A (6,6%) e em 6 do Grupo B (8,8%) (p = 1,0). Durante o seguimento, as recidivas foram diagnosticadas em 2 pacientes do Grupo A (4,7%) e em 5 do Grupo B (8%) (p = 0,7). Considerando tanto a doença persistente quanto a recorrente, doença estrutural foi detectada em 5 pacientes do Grupo A (11,1%) e em 11 do Grupo B (16,1%) (p = 0,58). Não houve nenhum caso de óbito relacionado à doença. Conclusão Nossos resultados não apoiam a hipótese de que a tireoidite linfocítica crônica esteja associada a um menor risco de doença persistente ou recorrente, pelo menos em pacientes com anticorpos antitireoglobulina persistentemente elevados após a terapia inicial do carcinoma papilífero de tireoide.

Influence of chronic lymphocytic thyroiditis on the risk of persistent and recurrent disease in patients with papillary thyroid carcinoma and elevated antithyroglobulin antibodies after initial therapy.

INTRODUCTION: In patients with papillary thyroid carcinoma who have negative serum thyroglobulin after initial therapy, the risk of structural disease is higher among those with elevated antithyroglobulin antibodies compared to patients without antithyroglobulin antibodies. Other studies suggest that the presence of chronic lymphocytic thyroiditis is associated with a lower risk of persistence/recurrence of papillary thyroid carcinoma. OBJECTIVE: This prospective study evaluated the influence of chronic lymphocytic thyroiditis on the risk of persistence and recurrence of papillary thyroid carcinoma in patients with negative thyroglobulin but elevated antithyroglobulin antibodies after initial therapy. METHODS: This was a prospective study. Patients with clinical examination showing no anomalies, basal Tg<1ng/mL, and elevated antithyroglobulin antibodies 8-12 months after ablation were selected. The patients were divided into two groups: Group A, with chronic lymphocytic thyroiditis on histology; Group B, without histological chronic lymphocytic thyroiditis. RESULTS: The time of follow-up ranged from 60 to 140 months. Persistent disease was detected in 3 patients of Group A (6.6%) and in 6 of Group B (8.8%) (p=1.0). During follow-up, recurrences were diagnosed in 2 patients of Group A (4.7%) and in 5 of Group B (8%) (p=0.7). Considering both persistent and recurrent disease, structural disease was detected in 5 patients of Group A (11.1%) and in 11 of Group B (16.1%) (p=0.58). There was no case of death related to the disease. CONCLUSION: Our results do not support the hypothesis that chronic lymphocytic thyroiditis is associated with a lower risk of persistent or recurrent disease, at least in patients with persistently elevated antithyroglobulin antibodies after initial therapy for papillary thyroid carcinoma.

Long-Term Follow-Up in Patients with Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Without a Suspicion of Persistent Disease in Postoperative Assessment.

The objective was to determine whether negative assessment after surgery is a predictor of no relevant change of the results in subsequent evaluations in patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Six months after surgery, "absence of persistent disease" was defined when concentration of thyroglobulin (Tg) is ≤2 ng/ml in patients undergoing total thyroidectomy and ≤10 ng/ml in those undergoing lobectomy, in the absence of antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) without abnormalities. One hundred thirteen patients met the definition of "absence of persistent disease". The patients were followed up for 18-150 months. None of the patients developed structural disease. In the 56 patients undergoing total thyroidectomy, 380 Tg measurements were obtained and an increase in concentrations was not observed in any of them. During the same period, 332 US scans were performed and a suspicious lymph node was detected on only one occasion, but was not metastatic on fine needle aspiration (FNA). In the 57 patients undergoing lobectomy, 382 Tg measurements were obtained and increases or persistent concentrations>10 ng/ml were not observed in any patient. During the same period, 376 US scans were performed and nodules with an indication for FNA were detected in 4 patients, but malignancy was not confirmed in any of them. Finally, TgAb were not elevated in any of the 762 measurements obtained from the 113 patients. After complete resection of NIFTP, negative postoperative assessment can be used to exclude the need for long-term repetition of these tests.