Celiac disease as differential diagnosis of normocalcemic hyperparathyroidism / Doença celíaca como diagnóstico diferencial do hiperparatireoidismo normocalcêmico

ABSTRACT There is no recommendation to investigate celiac disease (CD) in patients with elevated parathyroid hormone (PTH) and normal blood calcium if they are asymptomatic, especially if they do not have hypovitaminosis D. CD was diagnosed in a 30-year-old asymptomatic man without vitamin D deficiency, who had total calcium 9.2 mg/dl, 25-hydroxyvitamin D 36 ng/dl, PTH 112 pg/ml, total IgA 42 mg/dl, anti-tissue transglutaminase (tTG) IgA 22 U/ml. Duodenal biopsy by endoscopy confirmed CD. The patient started a gluten-free diet that was maintained. After six months, the patient had total calcium 9.5 mg/dl, 25-hydroxyvitamin D 42 ng/dl, and PTH 48 pg/ml. In most patients with elevated PTH and normal blood calcium, clinical history, assessment of renal function, vitamin D and phosphorus measurement, and calciuria define the cause of secondary hyperparathyroidism. However, in the few cases in which this initial investigation is negative, even asymptomatic individuals should be tested for CD antibodies before the diagnosis of normocalcemic primary hyperparathyroidism is made.

RESUMEN No hay recomendaciones para investigar enfermedad celíaca (EC) en pacientes con niveles elevados de hormona paratiroidea y calcio sérico normal si ellos son asintomáticos, principalmente si no tienen hipovitaminosis D. Reportamos un caso de EC diagnosticada en un hombre de 30 años, asintomático, sin deficiencia de vitamina D. Sus niveles séricos: calcio total 9,2 mg/dl, 25-hidroxivitamina D 36 ng/dl, hormona paratiroidea 112 pg/ml, inmunoglobulina A (IgA) total 42 mg/dl y anticuerpos anti-transglutaminasa tisular (tTG) IgA 22 U/ml. Biopsia duodenal por endoscopia confermó el diagnóstico de EC. El paciente empezó una dieta libre de gluten. Después de seis meses, el paciente presentó calcio total 9,5 ml/dl, 25-hidroxivitamina D 42 ng/dl y hormona paratiroidea 48 pg/ml. En la mayor parte de los pacientes con hormona paratiroidea elevada y calcio sérico normal, el historial clínico, la evaluación de la función renal y las mediciones de vitamina D, fósforo y calciuria definen la causa del hiperparatiroidismo secundario. No obstante, en los pocos casos en los cuales esa investigación inicial es negativa, incluso los individuos asintomáticos deben ser examinados para anticuerpos para EC antes que el diagnóstico de hiperparatiroidismo primario normocalcémico sea establecido.

RESUMO Não há recomendação para investigar doença celíaca (DC) em pacientes com paratormônio (PTH) elevado e cálcio sérico normal se eles são assintomáticos, principalmente se não têm hipovitaminose D. Relatamos um caso de DC diagnosticada em um homem de 30 anos, assintomático, sem deficiência de vitamina D. Os exames apresentaram cálcio total 9,2 mg/dl, 25-hidroxivitamina D 36 ng/dl, PTH 112 pg/ml, imunoglobulina da classe A (IgA) total 42 mg/dl e antienzima transglutaminase tecidual (tTG) IgA 22 U/ml. Biópsia duodenal por endoscopia confirmou o diagnóstico de DC. O paciente iniciou dieta sem glúten. Após seis meses, apresentou cálcio total 9,5 mg/dl, 25-hidroxivitamina D 42 ng/dl e PTH 48 pg/ml. Na maioria dos pacientes com PTH elevado e cálcio sérico normal, a história clínica, a avaliação da função renal e as dosagens de vitamina D, fósforo e calciúria definem a causa do hiperparatireoidismo secundário. Porém, nos poucos casos em que essa investigação inicial é negativa, até os indivíduos assintomáticos deveriam ser testados para anticorpos para DC antes de o diagnóstico de hiperparatireoidismo primário normocalcêmico ser firmado.

TRH stimulation test in patients with repeatedly elevated TSH and normal FT4 / Teste de estímulo com TRH em pacientes com TSH repetidamente elevado e T4L normal

ABSTRACT Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4). We aimed to evaluate the thyrotropin-releasing hormone (TRH) stimulation test in patients with repeatedly elevated TSH (up to 10 mIU/l) and normal FT4, but without apparent thyroid disease. Women with TSH > 4.5 and ≤ 10 mIU/l (in two measurements) and normal FT4 were selected. Women with a known non-thyroid cause of TSH elevation, those treated with anti-thyroid drugs, amiodarone, lithium, and those with a history of thyroidectomy, neck radiotherapy and 131I treatment were excluded. Seventy women had negative antithyroperoxidase antibodies. Ultrasonography revealed a eutopic thyroid, usual echogenicity, and a volume ≤ 15 ml, and they underwent the TRH stimulation test during initial evaluation. After stimulation with TRH, TSH > 30 mIU/l was observed in 38 women (expected response), while 32 women had TSH < 20 mIU/l (inadequate response). Age, basal TSH or thyroid volume did not differ between both groups, but FT4 concentrations were significantly lower in the first group. Follow-up was available for 66/70 women. Seven women developed a need for levothyroxine, all of them in the group with an adequate response to TRH [7/36 (19.4%) versus 0/30]. The results suggest that some cases of TSH elevation (even persistent) do not represent the early stage of thyroid insufficiency.

RESUMEN El hipotiroidismo subclínico (HSC) es definido por la elevación de los niveles de hormona tiroestimulante (TSH) con los niveles de tiroxina libre (T4L) dentro de rangos de normalidad. El objetivo de este reporte fue evaluar la prueba de estímulo con hormona liberadora de tirotropina (TRH) en pacientes con TSH persistentemente elevado (hasta 10 mUI/l) y T4L normal, pero sin enfermedad tiroidea aparente. Se eligieron mujeres con TSH > 4,5 y ≤ 10 mUI/l (en dos medidas) y T4L normal. Se excluyeron aquellas con causa no tiroidea conocida de alza de TSH además de las tratadas con medicamentos antitiroideos, amiodarona, litio y con historia de tiroidectomía, radioterapia cervical y tratamiento con 131I. Setenta mujeres presentaron anticuerpos antitiroperoxidasa negativos. La ecografía mostró tiroides eutópica, ecogenicidad usual y volumen ≤ 15 ml; todas se sometieron a la prueba de estímulo con TRH en la evaluación inicial. Tras estímulo con TRH, TSH > 30 mUI/l se observó en 38 mujeres (respuesta esperada), mientras 32 mujeres presentaron TSH < 20 mUI/l (respuesta inadecuada). El seguimiento estuvo disponible para 66/70 mujeres. Siete pacientes evolucionaron con necesidad de levotiroxina, todas ellas en el grupo con respuesta adecuada al TRH [7/36 (19,4%) versus 0/30]. Los resultados sugieren que algunos casos de alza de TSH (aunque persistente) no representan la fase inicial de una insuficiencia tiroidea.

RESUMO O hipotireoidismo subclínico (HSC) é definido pela elevação dos níveis de hormônio tireoestimulante (TSH) com os níveis de tiroxina livre dentro da normalidade (T4L). O objetivo deste relato foi avaliar o teste de estímulo com hormônio liberador de tirotrofina (TRH) em pacientes com TSH repetidamente elevado (até 10 mUI/l) e T4L normal, mas sem doença tireoidiana aparente. Mulheres com TSH > 4,5 e ≤ 10 mUI/l (em duas medidas) e T4L normal foram selecionadas. Foram excluídas aquelas com causa não tireoidiana conhecida de elevação do TSH, além das tratadas com medicamentos antitireoidianos, amiodarona, lítio e com histórico de tireoidectomia, radioterapia cervical e tratamento com 131I. Setenta mulheres apresentaram anticorpos antitireoperoxidase negativos. A ultrassonografia revelou tireoide eutópica, ecogenicidade usual e volume ≤ 15 ml; todas foram submetidas ao teste de estímulo com TRH na avaliação inicial. Após estímulo com TRH, TSH > 30 mUI/l foi observado em 38 mulheres (resposta esperada), enquanto 32 mulheres apresentaram TSH < 20 mUI/l (resposta inadequada). Idade, TSH basal ou volume da tireoide não diferiram entre os dois grupos, mas as concentrações de T4L foram significativamente menores no primeiro grupo. O acompanhamento foi disponível para 66/70 mulheres. Sete pacientes evoluíram com necessidade de levotiroxina, todas elas no grupo com resposta adequada ao TRH [7/36 (19,4%) versus 0/30]. Os resultados sugerem que alguns casos de elevação do TSH (mesmo persistente) não representam a fase inicial de uma insuficiência tireoidiana.

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.

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.

The risk of recurrence within the first five years is very low in patients with papillary thyroid carcinoma treated with radioiodine

Introduction: In older studies, the frequency of recurrence was approximately 20% among patients with papillary thyroid carcinoma (PTC) treated with radioactive iodine (RAI), but it is possible that many of these cases actually correspond to persistent disease and that the frequency of recurrence is overestimated. Objective: To reevaluate the frequency of recurrence within the first five years in patients with PTC adequately operated upon and treated with RAI who did not exhibit persistent disease (postoperative ultrasonography and post-therapy whole-body scanning showing no apparent tumor). Methods: We selected 293 patients [51 low risk (17.4%) and 242 intermediate risk (82.6%)] submitted to thyroidectomy followed by RAI who did not have persistent disease. Results: Five years after RAI therapy, a tumor was detected in 10 patients (3.4%) (lymph node metastases in seven, pulmonary metastases in two, and bone metastases in one). Structural recurrence was observed in only 2% of low-risk patients and in 3.3% of intermediate-risk patients, with disease progression in none of the low-risk patients and in only one (0.4%) of the intermediate-risk patients. Survival was 100%. Conclusion: The results of this study suggest that, after adequate total thyroidectomy and in the absence of persistent disease, the frequency of recurrence within the first five years is very low in patients with PTC (not high risk) treated with RAI.

Selective screening for thyroid dysfunction in pregnant women: How often do low-risk women cease to be treated following the new guidelines of the American Thyroid Association?

ABSTRACT Objective: Universal screening for thyroid dysfunction in pregnant women is not recommended by the American Thyroid Association (ATA) or the American Association of Clinical Endocrinologists (AACE). This study evaluated the frequency of pregnant women that would have an indication for levothyroxine (L-T4) according to the new ATA/AACE guidelines among low-risk women without an indication for screening with TSH. Subjects and methods: The sample consisted of 412 pregnant women ranging in age from 18 to 30 years. These women were considered to be at low risk for thyroid dysfunction according to ATA/AACE and would not be candidates for screening with TSH. Anti-thyroid peroxidase antibodies (TPOAb) and TSH were measured. Women who had TSH > 2.5 mIU/L or TPOAb in the first trimester were submitted to subsequent evaluations in the second and third trimester. Results: In the first trimester, none of the pregnant women would have L-T4 therapy "recommended" and treatment would be "considered" in only two. In the second trimester, pregnant women with positive TPOAb or TSH > 2.5 mIU/L in the first trimester (n = 30) were reevaluated. L-T4 treatment would be "recommended" in only one woman and would be "considered" in two others. The 28 women that were not treated in the second trimester were reevaluated in the third trimester, but none of them would have L-T4 "recommended". Conclusion: The findings of the study suggest that selective screening, recommended by ATA/AACE does not result in a significant loss of pregnant women with an indication for L-T4 treatment.

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.

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.

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.

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.

Is 131I ablation necessary for patients with low-risk papillary thyroid carcinoma and slightly elevated stimulated thyroglobulin after thyroidectomy?

ABSTRACT Objective This prospective study evaluated the recurrence rate in low-risk patients with papillary thyroid cancer (PTC) who presented slightly elevated thyroglobulin (Tg) after thyroidectomy and who did not undergo ablation with131I. Subjects and methods The study included 53 low-risk patients (nonaggressive histology; pT1b-3, cN0pNx, M0) with slightly elevated Tg after thyroidectomy (> 1 ng/mL, but ≤ 5 ng/mL after levothyroxine withdrawal or ≤ 2 ng/mL after recombinant human TSH). Results The time of follow-up ranged from 36 to 96 months. Lymph node metastases were detected in only one patient (1.9%). Fifty-two patients continued to present negative neck ultrasound. None of these patients without apparent disease presented an increase in Tg. Conclusions Low-risk patients with PTC who present slightly elevated Tg after thyroidectomy do not require ablation with 131I.

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. .