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.

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

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.

Automonitorização glicêmica: dificuldades na realização do procedimento por pacientes com diabetes mellitus / Glycemic self-monitoring: difficulties in the realization care procedures faced by diabetes mellitus patients / Autocontrol de glucemia: dificultades en la realización del procedimiento de pacientes con diabetes mellitus

Objetivo: avaliar a realização do procedimento de automonitorização glicêmica em pacientes com diabetes. Método: estudo quantitativo, tipo descritivo-exploratório e observacional. Pacientes adultos com diabetes foram observados enquanto realizavam o procedimento no serviço de atenção secundária, e cada aspecto era assinalado em um formulário. Os dados sofreram tratamento estatístico e discutidos a partir da literatura científica. Resultados: entre os 60 participantes, 63% eram mulheres; 53,3% aposentados; idade entre 35 e 60 anos (51,7%); 60% com ensino fundamental; 51,7% com renda de até um salário mínimo; 38% tinham diagnóstico de diabetes entre 11 e 20 anos e, destes, 93,3% desconheciam as metas glicêmicas; 86,7% não higienizavam as mãos antes e após o procedimento e não faziam o descarte correto dos resíduos; 91,7% não realizavam a limpeza do aparelho após o uso; 75% não registravam os resultados. Conclusão: os participantes apresentaram dificuldades e falhas na prática de automonitorização glicêmica, que podem comprometer a vigilância do seu real estado de saúde, emergindo a necessidade de capacitação, com vistas à eficácia do procedimento e prevenção de complicações, além de melhorias no controle da doença. Assim, cabe ao enfermeiro que atua nessa clientela empreender esforços que possibilitem a aquisição pelo paciente das habilidades necessárias ao exercício da técnica da automonitorização glicêmica e o despertar de sua consciência para os riscos à saúde provocados por uma ação incorreta

Objective: to evaluate the realization of glycemic self-monitoring in diabetes patients. Method: quantitative, descriptive-exploratory and observational study. Adult diabetes patients were observed while performing the procedure in a secondary care service, and each aspect was noted on a form. Data were treated statistically and discussed based on the scientific literature. Results: among the 60 participants, 63% were women; 53.3% were retired; the age varied between 35 and 60 years (51.7%); 60% had elementary education; 51.7% had an income of up to one minimum wage; 38% had received the diagnosis of diabetes between the ages of 11 and 20 years, and of these, 93.3% were unaware of glycemic goals; 86.7% did not clean their hands before and after the procedure and did not dispose of the waste properly; 91.7% did not clean the device after use; 75% did not record the results. Conclusion: the participants presented difficulties and flaws in the practice of glycemic self-monitoring that may compromise the surveillance of their real health status. There is thus a need for training to promote effective realization of the procedure and prevention of complications, as well as improvements in disease control. It is therefore up to nurses who assist this clientele to undertake efforts to make possible that patients gain the necessary skills to exercise the technique of glycemic self-monitoring and awakening of their awareness regarding the health risks implied in incorrect actions.

Long-term follow-up of patients with elevated IGF-1 and nadir GH > 0 4 µg/L but < 1 µg/L

ABSTRACT Objective To report the results of initial investigation and after 5 years of patients with a suspicious clinical scenario for acromegaly, elevated IGF-1, and nadir GH during an oral glucose tolerance test (OGTT) > 0.4 µg/L but < 1 µg/L. Subjects and methods Seventeen patients who had elevated IGF-1 (outside puberty and pregnancy) in two measurements and GH between 0.4 and 1 µg/L during OGTT were selected. Results During initial assessment, only one patient had microadenoma on magnetic resonance imaging (MRI) of the pituitary. In this patient, IGF-1 returned to normal spontaneously after 5 years. In the remaining 16 patients, spontaneous normalization of IGF-1 was observed in four and IGF-1 continued to be elevated in 12 after 5 years. None of the latter patients developed a phenotype of acromegaly, changes in physiognomy or increase in IGF-1 and no tumor was detected by imaging methods. Two patients had nadir GH < 0.4 µg/L, while the nadir GH remained between 0.4 and 1 µg/L in 10 patients. Conclusion In patients (notably young adult or adult women) without a typical phenotype in whom IGF-1 is measured due to a suspicious clinical scenario and is found to be slightly elevated, even if confirmed and in the absence of other causes, a nadir GH cut-off value of 0.4 µg/L instead of 1 µg/L in the OGTT might be inadequate for the diagnosis.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b)

ABSTRACT Objective To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). Subjects and methods The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). Results One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. Conclusion Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants)

ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

TSH reference values in the first trimester of gestation and correlation between maternal TSH and obstetric and neonatal outcomes: a prospective Brazilian study

ABSTRACT Objective To define the normal range of TSH in the first trimester of gestation and to evaluate the correlation between maternal TSH and obstetric and neonatal outcomes. Subjects and methods Prospective study. Women without known or clinically suspected thyroid disease and without risk factors for thyroid dysfunction, who became pregnant spontaneously and were initially evaluated up to week 12 of gestation, were included. Women with positive anti-thyroperoxidase antibodies, twin pregnancy, hyperemesis gravidarum, and trophoblastic disease were excluded. Results In the 660 pregnant women, the mean, median, and 2.5th and 97.5th percentiles of TSH were 0.9, 0.96, 0.04 and 2.68 mIU/L, respectively. TSH was undetectable in 2%, < 0.5 mIU/L in 17.4%, > 2 mIU/L in 9.7%, > 2.5 mIU/L in 4.7%, and > 3 mIU/L in 1%. None of the women received levothyroxine or antithyroid drugs during pregnancy. In addition, there was no difference in obstetric or neonatal outcomes when women with TSH ≤ 0.1, between 0.1 and 2.5, and between 2.5 and 4 mIU/L were compared. Conclusion In the population studied, the TSH value corresponding to the 97.5th percentile was 2.68 mIU/L in the first trimester of gestation.

Persistent and recurrent disease in patients with papillary thyroid carcinoma with clinically apparent (cN1), but not extensive, lymph node involvement and without other factors for poor prognosis

Objective Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics.Subjects and methods Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD.Results PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR.Conclusions The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

Laboratory investigation of acromegaly: Is basal or random GH > 0.4 µg/L in the presence of normal serum IGF-1 an important result?

Objective To determine the frequency of indication of the GH suppression test and pituitary magnetic resonance imaging (MRI) in patients with clinical suspicion of acromegaly with GH concentrations > 0.4 µg/L despite normal serum IGF-1. Subjects and methods A total of 160 patients with clinical suspicion of acromegaly with normal IGF-1 were studied. Results Basal GH > 0.4 µg/L was observed in 70/88 women (79.5%). Nadir GH > 0.4 µg/L was found in 21/70 women (30%) and these patients were submitted to MRI, which revealed a microadenoma in 2/21 women (9.5%). In these two women, IGF-1 continued to be normal in subsequent measurements and no clinical progression has been observed so far (time of follow-up until now 4 years). Basal GH > 0.4 µg/L was seen in 33/72 men (45.8%). Nadir GH was < 0.4 µg/L in all of them. Conclusions In patients with clinical suspicion of acromegaly, concern over GH concentration in the presence of normal IGF-1 results in the unwarranted complementary investigation in many cases, and even in possible equivocal diagnoses. It is only in exceptional cases that normal IGF-1 should not rule out acromegaly. Arch Endocrinol Metab. 2015;59(1):54-8 .

Is Doppler ultrasound of additional value to gray-scale ultrasound in differentiating malignant and benign thyroid nodules?

The objective of this study was to evaluate whether Doppler ultrasound (DUS) is of additional value to gray-scale ultrasound (GSUS) in predicting the benign or malignant nature of thyroid nodules. A total of 1,502 solid thyroid nodules ≥ 10 mm were evaluated. Suspicious vascularity (predominantly or exclusively central blood flow) was observed in only 5% of the nodules. This finding showed 96% specificity, but only 15% sensitivity. GSUS alone showed sensitivity and specificity of 88.7% and 68.2%, respectively, which did not improve with the addition of DUS (sensitivity of 89.4% and specificity of 66.4%). In non-suspicious nodules on GSUS, the type of vascularity on DUS did not modify the risk of malignancy, which was low. In suspicious nodules on GSUS, suspicious vascularity on DUS increased the risk of malignancy, but non-suspicious vascularity did not reduce this risk. DUS provided no additional value to GSUS in predicting the benign or malignant nature of thyroid nodules. Arch Endocrinol Metab. 2015;59(1):79-83.

Screening for acromegaly in adult patients not reporting enlargement of the extremities, but with arterial hypertension associated with another comorbidity of the disease / Rastreamento de acromegalia em pacientes adultos não relatando crescimento de extremidades, mas com hipertensão arterial associada a outra comorbidade da doença

Objective To determine the value of acromegaly screening in adult patients not reporting enlargement of the extremities, but who present arterial hypertension associated with at least one other comorbidity of the disease. Subjects and methods Patients seen by general practitioners at primary health care units were evaluated. Among the patients without extremity enlargement, those with recently diagnosed arterial hypertension associated with at least one other comorbidity were selected. Results A total of 1,209 patients were submitted to laboratory investigation. Elevated IGF‐1 was observed in 22 patients. Eighteen patients had adequate suppression of growth hormone (GH). No GH suppression was observed in four women with confirmed elevated IGF‐1. In the latter, IGF‐1 and nadir GH were only slightly elevated, magnetic resonance showed a normal pituitary, and chest and abdominal computed tomography revealed no tumor, and no intervention was performed. Conclusion In patients with arterial hypertension without known pituitary disease, acromegaly is unlikely in the absence of enlargement of the extremities. .

Objetivo Determinar o valor do rastreamento de acromegalia em pacientes adultos sem aumento de extremidades, mas com hipertensão arterial associada a pelo menos uma outra comorbidade da doença. Sujeitos e métodos Pacientes vistos por clínicos em unidades primárias de saúde foram avaliados. Entre pacientes sem aumento de extremidades, aqueles com hipertensão arterial diagnosticada recentemente e associada a pelo menos uma outra comorbidade foram selecionados. Resultados Um total de 1.209 pacientes foi submetido à investigação laboratorial. IGF‐1 foi elevado em 22 pacientes. Dezoito pacientes apresentavam supressão adequada do hormônio do crescimento (GH). Ausência de supressão do GH foi vista em quatro mulheres com IGF‐1 repetidamente elevado. Nestas, IGF‐1 e nadir do GH foram apenas discretamente aumentados, ressonância magnética revelou hipófise normal, tomografia computadorizada de tórax e abdome não revelaram tumor, e nenhuma intervenção foi realizada. Conclusão Em pacientes com hipertensão arterial sem doença hipofisária conhecida, acromegalia é improvável na ausência de aumento de extremidades. .

Should a family history of papillary thyroid carcinoma indicate more aggressive therapy in patients with this tumor? / História familiar de carcinoma papilífero de tireoide deve indicar terapia mais agressiva em pacientes com este tumor?

Objective To determine whether the currently recommended therapy for papillary thyroid carcinoma (PTC) that show no classical factors indicating a poor prognosis is also effective in cases with a family history of this tumor. Subjects and methods: Forty-two patients were studied; 10 were submitted to lobectomy and 32 to total thyroidectomy, including 23 without lymph node dissection and 9 with lymph node dissection. None of the patients received radioiodine or was maintained under TSH suppression. Results No case of recurrence was detected by imaging methods and there was no increase in thyroglobulin or antithyroglobulin antibodies during follow-up (24 to 72 months). Conclusion The treatment usually recommended for patients with PTC does not need to be modified in the presence of a family history of this tumor if no factors indicating a poor prognosis are present (tumor ≤2 cm, non-aggressive histology, no extensive extrathyroid invasion or important lymph node involvement, complete tumor resection, no evidence of persistent disease after surgery). .

Objetivo Avaliar se a terapia atualmente recomendada para o carcinoma papilífero de tireoide (CPT) sem fatores clássicos de pior prognóstico é efetiva também nos casos em que existe história familiar deste tumor. Sujeitos e métodos: Foram avaliados 42 pacientes; dez foram tratados com lobectomia e 32 com tireoidectomia total, sendo 23 sem dissecção de linfonodos e 9 com dissecção linfonodal. Nenhum paciente recebeu radioiodo ou foi mantido com TSH suprimido. Resultados Nenhuma recidiva nos métodos de imagem foi observada, nem incremento da tireoglobulina ou anticorpos antitireoglobulina durante o seguimento (24 a 72 meses). Conclusão Em pacientes com CPT, sem fatores de pior prognóstico (tumor ≤2 cm, histologia não agressiva, sem invasão extratireoidiana extensa ou acometimento linfonodal importante, ressecção tumoral completa, sem indícios de doença persistente após a cirurgia), o tratamento usualmente recomendado não precisa ser modificado quando há história familiar desse tumor. .

TSH reference range in older adults: a Brazilian study / Valores de referência do TSH em indivíduos idosos: um estudo brasileiro

Objective: To establish serum TSH reference values for a population of Brazilian elderly, and to compare them to those found in the adult population. Subjects and methods: Healthy volunteers aged 70 to 85 years, without known thyroid disease or risk factors for thyroid dysfunction, who did not use any medication that could potentially interfere with TSH, were selected. Subjects with goiter, palpable thyroid nodules, anti-thyroperoxidase antibodies, or altered free T4 were excluded. The sample consisted of 360 older adults (180 per sex). Results: TSH values corresponding to the 2.5th and 97.5th percentile of the sample were 0.2 and 4.62 mIU/L, respectively. TSH > 2.5 mIU/L was seen in 25.26% of the volunteers, > 3 mIU/L in 15.26%, and > 4 mIU/L in 6.1% of them. TSH values were slightly higher than those previously reported for adults (18-60 years). Conclusion: This study suggests an upper limit for normal TSH of approximately 4.6 mIU/L for the Brazilian elderly population. .

Objetivo: Estabelecer os valores de referência do TSH sérico em uma população idosa brasileira e compará-los ao encontrado na população adulta. Sujeitos e métodos: Foram selecionados voluntários saudáveis; com idade entre 70 e 85 anos; sem doença tireoidiana conhecida ou fatores de risco para disfunção tireoidiana; sem uso de medicamentos potencialmente interferentes no TSH. Indivíduos com bócio, nódulo tireoidiano palpável, anticorpos antitireoperoxidase ou T4 livre alterado foram excluídos. A amostra foi composta de 360 participantes (180 de cada sexo). Resultados: Os valores correspondentes aos percentis 2,5 e 97,5 da amostra foram 0,2 e 4,62 mIU/L, respectivamente. TSH > 2,5 mIU/L foi visto em 25,26% dos indivíduos, > 3 mIU/L em 15,26% e > 4 mIU/L em 6,1%. Os valores de TSH foram discretamente maiores que os encontrados previamente em indivíduos adultos (18-60 anos). Conclusão: Nosso estudo sugere para a população idosa brasileira o limite superior normal do TSH de aproximadamente 4,6 mIU/L. .

TSH reference values for adult Brazilian population / Valores de referência do TSH para a população brasileira adulta

OBJECTIVE: To establish limits of normal serum TSH for the adult (18 to 60 years) Brazilian population according to recommendations of the National Academy of Clinical Biochemistry. SUBJECTS AND METHODS: Healthy volunteers were evaluated and those fulfilling the following clinical criteria were selected: absence of known thyroid disease; no use of any interfering medications; no history of head and neck external radiotherapy, type 1 diabetes or autoimmune disease; no family history of thyroid disease, and absence of goiter or palpable nodules. Subjects with anti-thyroperoxidase antibodies and/or altered free T4 were excluded. The sample consisted of 960 subjects (480 males and 480 females). RESULTS: TSH values corresponding to the 2.5th and 97.5th percentiles of the sample were 0.43 and 3.24 mIU/L, respectively. TSH values > 2.5 mIU/L were observed in 9.15 percent of the volunteers and levels > 3 mIU/L in 3.11 percent. CONCLUSION: The present study suggests an upper limit of normal TSH of approximately 3.5 mIU/L.

OBJETIVO: Estabelecer os limites de normalidade do TSH sérico em uma população adulta (18 a 60 anos) brasileira, conforme as recomendações da National Academy of Clinical Biochemistry. SUJEITOS E MÉTODOS: Inicialmente foram avaliados voluntários saudáveis e selecionados aqueles sem doença tireoidiana conhecida, uso de medicamentos interferentes, passado de radioterapia externa de cabeça e pescoço, diabetes tipo 1 ou doença autoimune, história familiar de doença tireoidiana, bócio ou nódulos palpáveis. Indivíduos com anticorpos antitireoperoxidase (TPOAb) e/ou T4 livre alterado foram excluídos. A amostra foi composta de 960 participantes (480 de cada sexo). RESULTADOS: Os valores correspondentes aos percentis 2,5 e 97,5 da amostra foram 0,43 e 3,24 mIU/L, respectivamente. TSH > 2,5 mIU/L foi visto em 9,15 por cento dos indivíduos e > 3 mIU/L em 3,11 por cento. CONCLUSÃO: Nosso estudo sugere para a população adulta brasileira o limite superior normal do TSH de aproximadamente 3,5 mIU/L.

Cetoacidose diabética associada com síndrome de Guillain-Barré: relato de caso / Diabetes ketoacidosis associated with Guillan-Barré syndrome

A síndrome de Guillain-Barré (GBS) é uma desordem causada por exacerbada resposta imune aos processos infecciosos. O diabetes melito (DM) não é reconhecido como uma causa desta polirradiculopatia inflamatória, com poucos casos relatados na literatura sobre tal associação. Apresentamos um caso de uma paciente do sexo feminino, 44 anos, admitida com história recente de poliúria, polidipsia, perda de peso e astenia, glicemia de 562 mg/dL, em cetoacidose, sem foco infeccioso. Posteriormente desenvolveu quadro de polirradiculopatia, insuficiência respiratória e alteração liquórica compondo o quadro de GBS. No presente relato, a paciente recuperou-se plenamente do déficit neurológico, assim como da hiperglicemia, configurando quadro de diabetes tipo 2, com tendência à cetoacidose, evoluindo sem insulino-dependência.

Guillain-Barré syndrome (GBS) is a disorder caused by exaggerated immune response to infectious process. Diabetes Melito (DM) is not recognized as one cause of this inflammatory polyradiculoneuropathy with just a few cases of this association been described in the literature so far. We report here the case of a 44 years-old female patient admitted with a history of polyuria, polydipsia, weight loss, asthenia, hyperglycemia (562 mg/dL) and ketoacidosis without any infectious focus. The patient progressed with poliradiculopathy, respiratory insufficiency and liquoric alteration completing the picture of Guillain-Barré syndrome. The patient fully recovered from the neurologic deficit and then stopped with insulin therapy.

Diabetes auto-imune latente do adulto ou diabetes melito tipo 2 magro? / Latent autoimmune diabetes of adult or slim type 2 diabetes mellitus?

A prevalência do diabetes auto-imune latente do adulto (LADA) varia em virtude da população estudada, dos critérios usados e dos anticorpos avaliados. Em 256 pacientes com menos de 25 anos, encontramos 26 (10,2 por cento) com anticorpos anti-GAD (GADA) positivos, dos quais 16 (6,3 por cento) evoluíram sem necessidade de insulina inicialmente. Embora exista controvérsias, sugere-se como critérios diagnósticos de LADA: idade entre 25 e 65 anos; ausência de cetoacidose ou hiperglicemia sintomática no diagnóstico ou imediatamente após, sem necessidade de insulina por 6 a 12 meses; e presença de auto-anticorpos (especialmente GADA). A auto-imunidade e a resistência insulínica coexistem no LADA, e a contribuição desses fatores parece estar refletida nos títulos de GADA. Um subgrupo similar aos diabéticos tipo 2, fenotipicamente e na progressão para necessidade de insulina, parece ser melhor identificado pela presença de baixos títulos de GADA, sobretudo isolados. Por outro lado, indivíduos com altos títulos de GADA e múltiplos anticorpos apresentam fenótipo mais próximo do diabetes melito do tipo 1 (DM1) clássico e são de maior risco para falência prematura das células-beta. Comparados aos diabéticos GADA-negativos, pacientes com LADA apresentam maior prevalência de outros auto-anticorpos (anti-TPO, anti-21-hidroxilase e associados à doença celíaca) e maior freqüência de genótipos e haplótipos de risco para DM1. Pacientes com altos títulos de GADA podem ser beneficiados, retardando a falência das células-beta, com a insulinização precoce e evitando-se o uso de sulfoniluréias. Em oposição, pacientes com baixos títulos de GADA aparentemente não teriam prejuízos em serem conduzidos da mesma forma que pacientes portadores de diabetes melito tipo 2 (DM2) (GADA-negativos).

The prevalence of latent autoimmune diabetes of the adult (LADA) varies according to the population studied, criteria used and antibodies analyzed. In a series of 256 patients > 25 years, we found that 26 (10.2 percent) were anti-GAD antibody (GADA) positive and 16 of them (6.3 percent) progressed without initial insulin requirement. Although controversy exists, the following diagnostic criteria for LADA are suggested: age between 25 and 65 years; absence of ketoacidosis or symptomatic hyperglycemia at diagnosis or immediately thereafter, without insulin requirement for 6-12 months; and presence of autoantibodies (especially GADA). Autoimmunity and insulin resistance coexist in LADA and the contribution of these factors seems to be reflected in GADA titers. A subgroup, which is phenotypically and in terms of insulin requirement similar to type 2 diabetic patients, seems to be better identified based on the presence of low GADA titers, especially when these antibodies are present alone. On the other hand, subjects with high GADA titers and multiple antibodies show a phenotype close to that of classical DM 1 and are at a higher risk of premature beta-cell failure. Compared to GADA-negative diabetics, patients with LADA present a higher prevalence of other autoantibodies (anti-TPO, anti-21-hydroxylase and antibodies associated with celiac disease) and a higher frequency of genotypes and haplotypes indicating a risk for DM 1. Patients with high GADA titers may benefit from early insulinization and avoiding the use of sulfonylureas, delaying beta-cell failure. In contrast, patients with low GADA titers do not seem to have any disadvantage when managed as type 2 diabetic patients (GADA negative).

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization

OBJECTIVE: To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers). METHODS: Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis. RESULTS: Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later. CONCLUSION: We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

OBJETIVO: Determinar os parametros clínicos e laboratoriais e a progressão para a necessidade de insulina em dois grupos de pacientes com LADA, divididos de acordo com os títulos de GADA, e avaliar o benefício da insulinização precoce naqueles com risco elevado de falência prematura das células beta (títulos altos de GADA). MÉTODOS: Dentre os pacientes adultos com diabetes (DM) seguidos em nosso serviço e rastreados para GADA no diagnóstico, 54 foram diagnosticados com LADA e classificados como tendo títulos de GADA baixos (> 1 U/ml e < 17,2 U/ml) ou altos (> 17,2 U/ml). A comparação foi feita com 54 pacientes selecionados com DM tipo 2 (GADA-). Além disso, 24 pacientes com títulos de GADA > 20 U/ml, mas que não foram insulinizados no início, foram comparados com 16 outros que foram insulinizados desde o diagnóstico. RESULTADOS: A resistência à insulina foi maior no grupo GADA-, seguidos por aqueles com títulos baixos de GADA. O IMC, a frequência de hipertensão arterial, os triglicérides elevados e o HDL-colesterol reduzido foram menores no grupo com títulos elevados de GADA, sem diferença entre os GADA- ou com baixos títulos de GADA. O grupo com títulos elevados de GADA mostrou uma redução maior e menores níveis de peptídeo C, tendo requerido insulina mais precocemente durante o seguimento. Pacientes com títulos de GADA > 20 U/ml e precocemente insulinizados não apresentaram variações significantes nos níveis de peptídeo C, tiveram melhor controle glicêmico e requereram doses mais baixas de insulina do que aqueles que foram insulinizados mais tardiamente. CONCLUSÃO: Nós concordamos que pacientes com LADA devem ser diferenciados com base nos títulos de GADA e que aqueles com títulos > 20 U/ml beneficiam-se de insulinização precoce.