Obesity Influences T CD4 Lymphocytes Subsets Profiles in Children and Adolescent's Immune Response.

BACKGROUND: OBJECTIVES: Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation in adults with the disease. Because the profile of these cells is poorly understood in the pediatric population, this study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. METHODS: Using flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines, and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n = 20) with those with eutrophy group (EU group, n = 16). Plasma levels of cytokines in both groups were determined by CBA. RESULTS: The OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared with the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, whereas CTLA-4 is decreased in all subpopulations compared with the EU group. Furthermore, Th2, Th17, and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. CONCLUSIONS: CD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

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.

Subclinical Hypothyroidism with TSH>7 mIU/l and≤10 mIU/l and Coronary Artery Disease.

The association of subclinical hypothyroidism (SCH) with increased cardiovascular risk is controversial when thyroid-stimulating hormone (TSH) concentration is<10 mIU/l, as well as its association with a higher coronary artery calcium score (CACS) in individuals with low cardiovascular risk. This study evaluated coronary artery disease (CAD) by CACS in asymptomatic, low-cardiovascular risk women with SCH and TSH>7 mIU/l and≤10 mIU/l untreated for 5 years after diagnosis. The CACS was obtained for two groups of women with low cardiovascular risk. Group A consisted of 32 women with mild SCH (TSH>7 mIU/l and≤10 mIU/l) who remained untreated for 5 years, and group B consisted of 32 euthyroid women matched for age and body mass index to group A. The CACS ranged from 0 to 350 (median 0, 25-75% interval: 0-10) in group A and from 0 to 280 (median 0, 25-75% interval: 0-0) in group B. Scores>0 and≥10 were significantly more frequent in group A (40.6 vs. 12.5% and 25 vs. 3.1%, respectively). A CACS≥100 was also more frequent in group A (18.75 vs. 3.1%), but the difference was not significant (p=0.1). The results of the study suggest that long-term SCH with TSH>7 mIU/l and ≤ 10 mIU/l is associated with a higher risk of CAD in individuals≤65 years, even in those with low cardiovascular risk.

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.

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.

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Normocalcemic Primary Hyperparathyroidism in Adults Without a History of Nephrolithiasis or Fractures: A Prospective Study.

The prevalence and the diagnostic criterion of "normocalcemic" primary hyperparathyroidism (NPHPT) are still uncertain and there is no consensual definition. This prospective study evaluated the prevalence of NPHPT in 676 adults without a history of fractures or nephrolithiasis and who would be submitted to thyroidectomy, the impact of adopting different cut-off values for 25-hydroxyvitamin D and estimated glomerular filtration rate (eGFR), and the agreement between biochemical diagnosis and the surgical finding of altered parathyroid glands. NPHPT was diagnosed in patients with normal total and ionized calcium and elevated PTH (in 2 measurements) and without a known cause of secondary HPT, including eGFR<40 ml/min/1.73 m2 and 25-hydroxyvitamin D<20 ng/dl. The 4 parathyroid glands were fully explored in these patients. Forty-six patients (6.8%) had a laboratory diagnosis of NPHPT. Altered parathyroid glands were detected in only 4 patients, corresponding to 0.6% of all patients and to 8.7% of those with a biochemical diagnosis of NPHPT. The latter was confirmed in 0/174 men, 1/252 premenopausal women, and 3/250 postmenopausal women. Among the 42 patients with elevated PTH and without altered parathyroid glands, 25 had 25-hydroxyvitamin D between 20 and 30 ng/dl, 7 had eGFR between 40 and 60 ml/min/1.73 m2, and 9 had both. The prevalence of NPHPT was 0.74% in this adult population without a history of nephrolithiasis or fractures. The diagnostic criterion using eGFR>60 ml/min/1.73 m2 and 25-hydroxyvitamin D>30 ng/dl was more appropriate considering the agreement with the surgical finding of altered parathyroid glands.

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism.

OBJECTIVE: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. SUBJECTS AND METHODS: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. RESULTS: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). CONCLUSION: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

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.

Ultrasonography Classification of the American Thyroid Association for Predicting Malignancy in Thyroid Nodules >1cm with Indeterminate Cytology: A Prospective Study.

The objective of this prospective study was to evaluate the ultrasonography classification of the American Thyroid Association (ATA) for predicting malignancy in thyroid nodules >1 cm with indication for fine-needle aspiration (FNA) whose cytology was indeterminate. Additionally, the combination of the ATA classification with Doppler analysis was evaluated. All patients with thyroid nodules >1 cm were eligible. Each nodule was assigned to one of the ATA categories. Exclusively or predominantly intranodular vascularity was considered suspicious. One hundred and thirty-seven patients with 143 nodules underwent FNA and those with indeterminate cytology (Bethesda category III or IV) were selected. All patients were referred for surgery. Among the 143 nodules evaluated, 92 were benign, 33 were malignant, 13 were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 5 were tumors of uncertain malignant potential (TUMP). The rate of malignancy, including NIFTP and TUMP in this definition, was 80%, 42.8%, 13%, 10%, and 23% for nodules with a high suspicion, intermediate suspicion, low suspicion, very low suspicion, and undefined ultrasonographic pattern, respectively. Considering NIFPT and TUMP as benign, these rates were 72%, 22.4%, 4.3%, 0%, and 15.4%, respectively. The addition of Doppler analysis did not significantly improve the prediction of malignancy obtained with the ATA classification alone. The results of this prospective study show the usefulness of the ATA ultrasonographic classification for predicting malignancy specifically in thyroid nodules >1 cm with indeterminate cytology. The ATA category of the nodule should influence the decision for follow-up, molecular tests, or surgery.

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.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study.

OBJECTIVE: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. SUBJECTS AND METHODS: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. RESULTS: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). CONCLUSIONS: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Serum TSH level stability after 5 years in euthyroid adults at low risk for thyroid dysfunction.

OBJECTIVE: To evaluate changes in thyroid function after 5 years, the interval proposed for new assessment, in initially euthyroid adults. SUBJECTS AND METHODS: Initially, 1,426 apparently healthy adults considered low risk for thyroid dysfunction, were evaluated by measurement of TSH. After 5 years, 1,215 (85.2%) subjects were reevaluated. RESULTS: After 5 years, four subjects were receiving levothyroxine (L-T4) replacement therapy and 25 others had TSH > 4 mIU/L, only two of them with TSH > 10 mIU/L. All of these subjects had TSH > 3 mIU/L in the initial evaluation. During reassessment, none of the subjects had been or was treated for hyperthyroidism and 22 had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). Nineteen of these subjects had TSH ≤ 0.6 mIU/L in the initial evaluation. Among the 1,098 subjects with TSH between 0.6 and 3 mIU/L in the initial evaluation, reassessment showed that none of the subjects was using L-T4; only three had TSH > 4 mIU/L (none of them > 10 mIU/L); none had been or was treated for hyperthyroidism, and only three had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). These results did not differ between men and women or between subjects ≤ 60 and > 60 years. CONCLUSION: Repeat TSH measurement within an interval of only 5 years would not be cost-effective in adults without known thyroid disease or risk factors for dysfunction who exhibit TSH between 0.6 and 3 mIU/L.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study

ABSTRACT Objective: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. Subjects and methods: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. Results: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). Conclusions: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Serum TSH level stability after 5 years in euthyroid adults at low risk for thyroid dysfunction

ABSTRACT Objective: To evaluate changes in thyroid function after 5 years, the interval proposed for new assessment, in initially euthyroid adults. Subjects and methods: Initially, 1,426 apparently healthy adults considered low risk for thyroid dysfunction, were evaluated by measurement of TSH. After 5 years, 1,215 (85.2%) subjects were reevaluated. Results: After 5 years, four subjects were receiving levothyroxine (L-T4) replacement therapy and 25 others had TSH > 4 mIU/L, only two of them with TSH > 10 mIU/L. All of these subjects had TSH > 3 mIU/L in the initial evaluation. During reassessment, none of the subjects had been or was treated for hyperthyroidism and 22 had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). Nineteen of these subjects had TSH ≤ 0.6 mIU/L in the initial evaluation. Among the 1,098 subjects with TSH between 0.6 and 3 mIU/L in the initial evaluation, reassessment showed that none of the subjects was using L-T4; only three had TSH > 4 mIU/L (none of them > 10 mIU/L); none had been or was treated for hyperthyroidism, and only three had TSH < 0.4 mIU/L (none of them < 0.1 mIU/L). These results did not differ between men and women or between subjects ≤ 60 and > 60 years. Conclusion: Repeat TSH measurement within an interval of only 5 years would not be cost-effective in adults without known thyroid disease or risk factors for dysfunction who exhibit TSH between 0.6 and 3 mIU/L.