Evaluation of circulating cell free DNA in plasma as a biomarker of different thyroid diseases / Avaliação do DNA circulante livre de células no plasma como um biomarcador de diferentes doenças da tireoide

Abstract Introduction: Many studies have been done on proteomics, genomics, epigenetic, immunogenetics in many body fluids. Among these, circulating cell-free DNA (ccfDNA) entered the literature in 1948, but it has not been studied for many years due to technological deficiencies. Following recent advances, geno-metastasis has been mentioned and new research is needed in this area. ccfDNA is known to be an important biomolecule in this regard. Objective: The presence of cell-free DNA in the circulatory system may offer a tremendous opportunity to provide novel biomarkers for thyroid diseases. This experimental study was conducted to determine the amount of ccfDNA in different thyroid diseases, then to evaluate whether the ccfDNA concentration varied between the disease groups and control group. Methods: In total, we included 121 individuals in the present study. We collected blood samples and then determined the ccfDNA concentration in plasma of collected blood samples from three groups: thyroiditis (n = 33), benign (n = 37), and malignant (n = 30) and from a control group (n = 21). Results: The median values of the ccfDNA groups were found as 1610, 1665, 1685 and 576 ng/mL for the thyroiditis, benign, malign, and control groups, respectively. Findings showed that the ccfDNA of the three groups was significantly higher than the control (p < 0.0001). Each group was compared in terms of ccfDNA and the p-values of benign-thyroiditis, benign-malign, and thyroiditis-malign were 0.09, 0.65, and 0.29, respectively. Conclusions: The clear differences between thyroid diseases and controls suggest that ccfDNA is worthy of attention as a biomarker for further evaluation of different thyroid diseases. Likewise, it might indicate a clear tendency that ccfDNA can also be used to distinguish different thyroid diseases.

Resumo Introdução: Muitos estudos foram realizados em proteômica, genômica, epigenética e imunogenética em vários fluidos corporais. Entre esses, o DNA circulante livre de células (cfDNA) despontou na literatura em 1948, mas não foi estudado por muitos anos devido a deficiências tecnológicas. Após recentes avanços, a genometástase é mencionada e novas pesquisas tornam-se necessárias nessa área. Nesse sentido, o cfDNA é conhecido por ser uma importante biomolécula. Objetivo: A presença de DNA livre de células no sistema circulatório pode oferecer uma excelente oportunidade para fornecer novos biomarcadores para doenças da tireoide. Este estudo experimental foi conduzido para determinar a quantidade de cfDNA em diferentes doenças da tireoide e então avaliar se a concentração de cfDNA variou entre os grupos com doença e o grupo controle. Método: No total, 121 indivíduos foram incluídos no estudo. Coletamos amostras de sangue e, em então, determinamos a concentração de cfDNA no plasma de amostras de sangue de três grupos: tireoidite (n = 33), benigno (n = 37) e maligno (n = 30) e de um grupo controle (n = 21). Resultados: As medianas dos valores dos grupos de cfDNA foram de 1.610, 1.665, 1.685 e 576 ng/mL para os grupos tireoidite, benigno, maligno e controle, respectivamente. Os achados mostraram que o cfDNA dos três grupos com doença era significativamente maior do que o do grupo controle (p < 0,0001). Cada grupo foi comparado em termos de cfDNA e os p-valores de benigno-tireoidite, benigno-maligno e tireoidite-maligno foram de 0,09, 0,65 e 0,29, respectivamente. Conclusões: Como resultado, as óbvias diferenças entre as doenças da tireoide e os controles sugerem que o cfDNA é digno de atenção como um biomarcador para avaliação adicional das diferentes doenças da tireoide. Da mesma forma, isso pode indicar uma clara tendência de que o cfDNA também pode ser utilizado para distinção das diferentes doenças da tireoide.

Prevalence of antithyroperoxidase antibodies in a multiethnic Brazilian population: The ELSA-Brasil Study

ABSTRACT Objective In this study, we aimed to describe the prevalence and distribution of positive antithyroperoxidase antibodies (TPOAb) according to sex, age strata, and presence of thyroid dysfunction using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Materials and methods Thyroid hormone tests were obtained from each study participant at baseline. Levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured using a third-generation immunoenzymatic assay. Antithyroperoxidase antibodies were measured by electrochemiluminescence and were considered to be positive when ≥ 34 IU/mL. Results The prevalence of TPOAb among 13,503 study participants was 12%. Of participants with positive TPOAb, 69% were women. Almost 60% of the individuals with positive TPOAb were white. The presence of positive TPOAb was associated with the entire spectrum of thyroid diseases among women, but only with overt hyperthyroidism and overt hypothyroidism in men. Conclusion The distribution of positive TPOAb across sex, race, age, and thyroid function in the ELSA-Brasil study is aligned with the worldwide prevalence of positive TPOAb reported in iodine-sufficient areas. In women, the presence of TPOAb was related to the entire spectrum of thyroid dysfunction, while in men, it was only related to the occurrence of overt thyroid disease.

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.

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.

Thyrotropin and free thyroxine levels and coronary artery disease: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Data on the association between subclinical thyroid dysfunction and coronary artery disease (CAD) is scarce. We aimed to analyze the association between thyroid function and CAD using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We included subjects with normal thyroid function (0.4-4.0 mIU/L, and normal free thyroxine, FT4, or 0.8 to 1.9 ng/dL), subclinical hypothyroidism (SCHypo; TSH>4.0 mIU/L and normal FT4), and subclinical hyperthyroidism (SCHyper; TSH<0.4 mIU/L and normal FT4) evaluated by coronary computed tomography angiography. We excluded individuals using medications that interfere in thyroid function or with past medical history of cardiovascular disease. Logistic regression models evaluated the presence of CAD, segment involvement score (SIS) >4, and segment severity score (SSS) >4 of coronary arteries as the dependent variables, and quintiles of TSH and FT4 as the independent variables, adjusted for demographical data and cardiovascular risk factors. We included 767 subjects, median age 58 years (IQR=55-63), 378 (49.3%) women, 697 euthyroid (90.9%), 57 (7.4%) with SCHypo, and 13 (1.7%) with SCHyper. No association between TSH and FT4 quintiles and CAD prevalence was noted. Similarly, no association between TSH levels and the extent or severity of CAD, represented by SIS>4 and SSS>4 were seen. Restricting analysis to euthyroid subjects did not alter the results. TSH levels were not significantly associated with the presence, extent, or severity of CAD in a middle-aged healthy population.

Thyroid disorders in obese patients. Does insulin resistance make a difference?

ABSTRACT Objective: The aim of this study was to evaluate the association between insulin resistance and thyroid pathology in obese patients, and compare the results between insulin-resistant and noninsulin-resistant patients. Subjects and methods: Obese/nondiabetic patients, aged 18-70 years, attending the outpatient endocrinology service for 2 years were consecutively included. We evaluated the patients' fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), thyroid-stimulating hormone (TSH), free thyroxine (FT4), antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), and thyroid ultrasound. Results: We included 82 patients with a mean age 44.21 ± 12.67 years. The thyroid disorders encountered and their prevalences were: hypothyroidism (14.6%, 95% confidence interval [CI] 8.6-23.8%), hyperthyroidism (1.2%, 95% CI 2.0-6.6%), goiter (28.0%, 95% CI 19.5-3.6%), thyroid nodules (35.4%, 95% CI 25.9-46.2%), and Hashimoto's thyroiditis (32.9%, 95% CI 23.7-43.7%). HOMA-IR correlated positively with TSH levels (r = 0.24, p = 0.028), and this correlation remained after adjustment for body mass index (BMI), waist/hip ratio (WHR), serum cortisol, subcutaneous fat thickness (SFT), visceral fat thickness (VFT), triglycerides, γ-glutamyl transpeptidase (GGT), and alanine aminotransferase (ALT) in multivariate regression analysis (b = 0.207, 95% CI, 0.09-0.385, p = 0.023). TSH levels were significantly higher in patients with HOMA-IR ≥ 2.5 than in those with HOMA-IR < 2.5 (2.03 μIU/mL, interquartile range [IQR] 1.59-2.69 μIU/mL) versus 1.59 μIU/mL, IQR 0.94-2.26 μIU/mL, p = 0.023). Conclusions: The most prevalent thyroid disorder in patients attending our endocrinology clinic for investigation of obesity was thyroid nodules. One in seven patients had hypothyroidism. Our findings suggest that TSH levels correlate with insulin resistance in obese patients.

Novel immunoassay for TSH measurement in rats

ABSTRACT Measuring thyroid hormones is an important aspect for the study of metabolism and for monitoring diseases in both human and animal models. The traditional method for hormone measurement in rats is the radioimmunoassay (RIA). However, the RIA is associated with some practical disadvantages, including the use of radioactive material, the need for specialized equipment and expert staff, the short shelf-life of kits according to the half-life of the radioisotope and high costs. The objective of this study was to develop a new cost-effective method for measuring TSH levels in rats that avoids the use of radioactive material. We developed an in-house competitive immunoassay using a reference standard, polyclonal antibody produced in rabbits and biotinylated antigen. This method was tested in 64 Wistar rats that were divided into a control group (n = 41) and a group with hypothyroidism (n = 23). Our assay demonstrated an analytical sensitivity of 0.24 ng/mL (n = 12) and an intra-assay coefficient of variation (CV) of 8.9% for sera with TSH levels of 1.5 ng/mL and 13.2% for sera with TSH levels of 17.5 ng/mL (n = 14). The inter-assay CV was 13.5% for sera with TSH levels of 1.4 ng/mL and 14.5% for TSH levels of 18.2 ng/mL (n = 5). The analysis of mean TSH levels in control rats (5.06 ± 0.5701) and hypothyroid rats (51.09 ± 5.136) revealed a statistically significant difference (p < 0.001) between the groups. This method showed good sensitivity, can be automated and is low-cost compared with RIA. Our method offers a viable alternative for TSH measurement in rats.

Does insulin resistance increase thyroid volume in patients with polycystic ovary syndrome?

ABSTRACT Objective To investigate the effect of gonadotropin, sex hormone levels and insulin resistance (IR) on thyroid functions and thyroid volume (TV) in polycystic ovary syndrome (PCOS). Subjects and methods 69 new diagnosed PCOS patients (age 24.82 ± 6.17) and 56 healthy control female (age 26.69 ± 5.25) were involved to the study. Fasting plasma glucose, lipid profile, insulin, thyroid stimulating hormone (TSH), free thyroxine (fT4), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone levels and urine iodine were measured in all participants. Thyroid and pelvic ultrasound were performed in all participants. Results Insulin, HOMA-IR, LH, E2 and TV were higher in PCOS group (p < 0.05). TV was significantly higher in PCOS patients with IR compared to non-IR PCOS patients (p < 0.001), while TSH, fT4, and urine iodine levels were similar between these groups (p > 0.05). There was a negative correlation between E2 and TSH (p < 0.05) and a positive correlation between TSH and TV (p < 0.05). There was a significant positive correlation between TV and LH, insulin, HOMA-IR (p < 0.05). Conclusion This study showed that TV was increased in patients with insulin resistance but differences in TSH and LH levels may affect TV changes as well.

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.

Clinical and laboratory characteristics of patients with thyroid diseases with and without alanine aminotransferase levels above the upper tertile – Cross-sectional analytical study

Objective Thyroid disease affects 6.6% of the general population. The liver is fundamental in metabolizing thyroid hormones, and hepatocytes are often affected in thyroid disease. We aimed to compare clinical and laboratory parameters among thyroid disease patients with alanine aminotransferase (ALT) levels above vs. below the upper tertile. Subjects and methods A retrospective cross-sectional analytical study was conducted in the endocrinology clinic at Polydoro Ernani de São Thiago University Hospital. Patients with thyroid disease between August 2012 and January 2014 were included in the study. Clinical and laboratory parameters were collected from medical records. Results One hundred patients were included, of which 14.0% were male, with a mean age of 49.1 ± 14.4 years. ALT levels ranged from 9 to 90 U/L, and the ALT upper tertile was defined as 0,64 times the upper normal limit (xUNL). Patients with ALT levels above the upper tertile exhibited a higher proportion of systemic arterial hypertension (SAH), a higher mean abdominal circumference and a higher frequency of elevated TSH levels than did patients with ALT levels below the upper tertile. In multivariate analysis, ALT ≥ 0.64 (xUNL) was independently associated with abdominal circumference (odds ratio [OR] = 0.087, 95% confidence interval [CI] 0012-0167, P = 0.022). ALT (xUNL) correlated positively with total cholesterol (r = 0.213, P = 0.042). Conclusions In patients with thyroid diseases, it was observed that those with ALT above the upper tertile are associated with abdominal circumference and ALT levels correlate with total cholesterol.

Insights into the posttranslational structural heterogeneity of thyroglobulin and its role in the development, diagnosis, and management of benign and malignant thyroid diseases

ABSTRACT Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes.

Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico / High frequency of thyroid abnormalities in polycystic ovary syndrome

La prevalencia de trastornos tiroideos (TT) no ha sido suficientemente evaluada en mujeres con síndrome de ovario poliquístico (SOP). El propósito de esta investigación fue examinar dicha relación. En este estudio prospectivo de diseño caso-control, se incluyeron 194 mujeres. El grupo SOP consistió en 142 pacientes diagnosticadas por criterios Rotterdam 2003, y el grupo control incluyó a 52 mujeres sanas apareadas por edad. Se extrajeron muestras de sangre en ayuno para dosajes de T4 libre, tirotrofina, anticuerpos antiperoxidasa (ATPO), insulinemia y glucemia y se calculó el índice HOMA. Un total de 52 pacientes con SOP presentó autoinmunidad tiroidea (AIT+) y/o hipotiroidismo subclínico (HSC) (36.6%) (TT+) en comparación con 7 mujeres del grupo de control (13.5%), lo que representa una frecuencia cinco veces mayor de TT en pacientes con SOP en comparación con los controles (odds ratio ajustado: 5.6; IC 95%: 2.1-14.9; p < 0.001). Las pacientes TT+ tuvieron valores de insulinemia y HOMA significativamente más altos que aquellas sin trastornos tiroideos (TT-) (p < 0.05).Este estudio muestra una alta tasa de TT en mujeres con SOP asociada a mayores niveles de insulinemia y HOMA. Teniendo en cuenta que el SOP, el hipotiroidismo y la autoinmunidad tiroidea pueden tener un profundo impacto en la salud reproductiva, nuestros datos sugieren que las pacientes con SOP deberían ser evaluadas para descartar TT.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p < 0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities(p < 0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Association between anaerobic components of the maximal accumulated oxygen deficit and 30-second Wingate test

The purpose of this study was to analyze the relationship between the anaerobic components of the maximal accumulated oxygen deficit (MAOD) and of the 30-second Wingate anaerobic test (30-WAnT). Nine male physical education students performed: a) a maximal incremental exercise test; b) a supramaximal constant workload test to determine the anaerobic components of the MAOD; and c) a 30-WAnT to measure the peak power (PP) and mean power (MP). The fast component of the excess post-exercise oxygen consumption and blood lactate accumulation were measured after the supramaximal constant workload test in order to determine the contributions made by alactic (ALMET) and lactic (LAMET) metabolism. Significant correlations were found between PP and ALMET (r=0.71; P=0.033) and between MP and LAMET (r=0.72; P=0.030). The study results suggested that the anaerobic components of the MAOD and of the 30-WAnT are similarly applicable in the assessment of ALMET and LAMET during high-intensity exercise.

Reference interval for thyrotropin in a ultrasonography screened Korean population

BACKGROUND/AIMS: The diagnostic accuracy of thyroid dysfunctions is primarily affected by the validity of the reference interval for serum thyroid-stimulating hormone (TSH). Thus, the present study aimed to establish a reference interval for TSH using a normal Korean population. METHODS: This study included 19,465 subjects who were recruited after undergoing routine health check-ups. Subjects with overt thyroid disease, a prior history of thyroid disease, or a family history of thyroid cancer were excluded from the present analyses. The reference range for serum TSH was evaluated in a normal Korean reference population which was defined according to criteria based on the guidelines of the National Academy of Clinical Biochemistry, ultrasound (US) findings, and smoking status. Sex and age were also taken into consideration when evaluating the distribution of serum TSH levels in different groups. RESULTS: In the presence of positive anti-thyroid peroxidase antibodies or abnormal US findings, the central 95 percentile interval of the serum TSH levels was widened. Additionally, the distribution of serum TSH levels shifted toward lower values in the current smokers group. The reference interval for TSH obtained using a normal Korean reference population was 0.73 to 7.06 mIU/L. The serum TSH levels were higher in females than in males in all groups, and there were no age-dependent shifts. CONCLUSIONS: The present findings demonstrate that the serum TSH reference interval in a normal Korean reference population was higher than that in other countries. This result suggests that the upper and lower limits of the TSH reference interval, which was previously defined by studies from Western countries, should be raised for Korean populations.

Clinical evaluation with self-sequential longitudinal reference intervals: pregnancy outcome and neonatal thyroid stimulating hormone level associated with maternal thyroid diseases / Evaluación clínica con intervalos de referencia longitudinal auto-secuencial: evolución clínica del embarazo y niveles de la hormona estimulante de la tiroides en neonatos asociados con enfermedades tiroideas maternas

OBJECTIVE: We attempted to evaluate maternal thyroid function in a new self-sequential longitudinal reference interval (SLRI) which we established recently. By this method, we analysed the correlation between pregnancy outcome, neonatal thyroid stimulating hormone (TSH) level and maternal thyroid diseases. METHODS: A total of 1744 pregnant women participated in the study and 1747 babies were born from those women (three bore twins). The levels of TSH, free thyroxine (FT4) and thyroid peroxidase antibodies (TPO-Ab) of mothers were quantified by electrochemistry immunoassay (ECL). The levels of neonatal blood TSH were detected by time-resolved fluorescence immunoassay (TRFIA). All data were collected and statistically analysed by SPSS 13.0 software. RESULTS: With our new SLRI method, we found that 0.11%~3.84% pregnant women would get thyroid diseases. Subclinical hypothyroidism was the most common maternal thyroid disorder. Being positive for thyroid peroxidase antibodies was a significant risk factor of subclinical hypothyroidism during pregnancy. The median, P2.5~P97.5, and interquartile range (IQR) of neonatal TSH (N-TSH) of 1747 babies were 2.72 mIU/L, 0.10~8.01 mIU/L and 2.62 mIU/L, respectively; 28.6% of pregnant women with thyroid diseases developed pregnancy complications. The prevalence was significantly higher than in the normal thyroid function group (p< 0.001). The levels of N-TSH were low correlated with maternal TSH levels (p < 0.05), but there were no significant correlations between N-TSH and maternal FT4 and maternal TPO-Ab (p > 0.05). CONCLUSIONS: Thyroid disorders, especially subclinical hypothyroidism, are common in pregnant women. These disorders are associated with pregnancy and fetal outcome. Routine maternal thyroid function screening is important and should be recommended.

OBJETIVO: Intentamos evaluar la función tiroidea materna en un nuevo intervalo de referencia longitudinal auto-secuencial (SLRI) que establecimos recientemente. Por este método, analizamos la correlación entre el resultado del embarazo, el nivel de la hormona estimulante de la tiroides (TSH) en neonatos, y las enfermedades tiroideas maternas MÉTODOS: Un total de 1744 mujeres embarazadas participó en el estudio y 1747 bebés nacieron de esas mujeres (tres de ellas tuvieron gemelos). Los niveles de TSH, la tiroxina libre (FT4), y los anticuerpos de la peroxidasa tiroidea (TPO-Ab) de las madres, fueron cuantificados mediante inmunoensayo electroquímico (ECL). Los niveles de TSH en la sangre de los neonatos, fueron determinados mediante inmunoensayo por fluorescencia resuelto en el tiempo (TRFIA). Todos los datos fueron recogidos y analizados estadísticamente usando el software SPSS 13.0 RESULTADOS: Con nuestro nuevo método SLRI, encontramos que 0.11%~3.84% de las mujeres embarazadas contraerán enfermedades tiroideas. El hipotiroidismo subclínico fue el trastorno de la tiroides materna más común. Ser positivo a los anticuerpos de la peroxidasa tiroidea fue un factor de riesgo significativo del hipotiroidismo subclínico durante el embarazo. La mediana, P2.5~P97.5, y el rango intercuartil (IQR) de la TSH (N-TSH) neonatal de los 1747 bebés fueron 2.72 mIU/L, 0.10~8.01 mIU/L y 2.62 mIU/L respectivamente. El 28.6% de las mujeres embarazadas que tenían enfermedades tiroideas, desarrollaron complicaciones del embarazo. La prevalencia fue significativamente más alta que en el grupo con función tiroidea normal (p < 0.001). Los niveles de N-TSH fueron bajos en correlación con los niveles de TSH maternos (p < 0.05), pero no hubo ninguna correlación significativa entre la N-TSH y la FT4 materna, y la TPO-Ab materna (p > 0.05). CONCLUSIÓNS: Los trastornos tiroideos, especialmente el hipotiroidismo, son comunes en las mujeres embarazadas.Estos trastornos se hallan asociados con el resultado del embarazo y el resultado fetal. El tamizaje de rutina de la función tiroidea materna es importante y debe recomendarse.

Perfil dos hormônios da tireoide em pacientes com câncer de mama em estado de menopausa / Thyroid hormone profile in breast cancer patients in postmenopause

OBJETIVO: Verificar o perfil dos hormônios tireóideos (HTs) em pacientes pós-menopausa portadoras de carcinoma de mama (CaM). SUJEITOS E MÉTODOS: Participaram 12 pacientes com CaM em estádio I ou II sem intervenções que pudessem interferir na progressão tumoral e um grupo controle com 18 pacientes em pós-menopausa sem CaM. Foram dosados os níveis séricos de anticorpo antitiroperoxidase (TPOAB), hormônio estimulante da tireoide (TSH), tiroxina livre (T4L), estradiol (E2), hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) antes e após a cirurgia, e realizada a imunoistoquímica dos receptores de estrógeno (ER) e progesterona (PR). RESULTADOS: Quatro pacientes com CaM apresentaram alterações do perfil hormonal tireoidiano: dois hipertireoidismo, um hipotireoidismo e positividade TPO-AB, todas com ER e PR positivos. Os níveis de TSH dessas pacientes não foram diferentes dos níveis encontrados no grupo controle (1,89 ± 1,56 vs. 2,86 ± 3,12 mUI/mL), porém os níveis de T4L nas pacientes com CaM foram estatisticamente maiores que o controle (1,83 ± 0,57 vs. 1,10 ± 0,20 ng/dL). CONCLUSÃO: Esses resultados reforçam a necessidade de avaliação do status tireoidiano em pacientes com CaM, uma vez que, na ausência de E2, mudanças clínicas nos HTs podem atuar em vias controladas pelo E2.

OBJECTIVE: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). SUBJECTS AND METHODS: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. RESULTS: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL). CONCLUSION: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes.

Alta frecuencia de patología tiroidea funcional y autoinmune en mujeres embarazadas chilenas catalogadas como sanas / High frequency of functional and autoimmune thyroid disease in women classified as healthy Chilean pregnant

Background: Untreated functional thyroid diseases are a risk factor for maternal and fetal complications during pregnancy. Aim: To determine the frequency of functional or autoimmune thyroid disease in healthy women during the first trimester of pregnancy. Subjets and Methods: healthy pregnant women attending a routine consult during their first trimester of pregnancy were studied. Thyroid stimulating hormone (TSH), total and free thyroxin (T4) anti-thyroid peroxidase (TPO) antibodies and spot urine iodine levels were measured. The reference ranges provided by the Atlanta Georgia Consensus in 2004 were used as normal values. A urine iodine concentration < 150 ug/L was considered low. Results: One hundred women age 30 +/- 5 years with a mean gestational age of 8,8 +/- 1,9 weeks, were studied. The frequencies of subclinical hypothyroidism, clinical hypothyroidism, isolated low thyroxin lecels, high antiTPO antibodies and low urine iodine levels were 19, 2, 3, 13 and 15 percent, respectively. Women with high TSH levels had lower total and free T4 levels. Conclusions: Twenty one percent of this sample of apparently healthy pregnant women had a clinical or subclinical hypothyroidism.

Vitiligo na criança e doença da tireóide / Childhood vitiligo and thyroid disease

A associação entre vitiligo e tireoidopatia na criança é discutível. Cinquenta crianças com vitiligo e 40 sem vitiligo foram submetidas às dosagens séricas de anticorpos antitireoide e hormônio tireoestimulante. Um caso (grupo teste) e um caso controle mostraram títulos de TSH acima do limite normal; o vitiligo não representou maior risco para tireoidopatia.

The association of vitiligo / thyroid disease in childhood is debatable; 50 children with vitiligo and 40 without it were submitted to serum dosage of antithyroid antibodies and thyrostimulating hormone. One case (test group) and one control showed a serum titer of TSH above the normal limit; vitiligo did not represent a greater risk for thyroid disease.

Coagulation profiles in hypothyroid and hyperthyroid female patients in Sudan

To evaluate disturbances in the coagulation system in female patients with thyroid disorders in order to assess the effects of thyroid diseases on coagulation parameters. This study was conducted in Khartoum state, the national capital of Sudan from February 2007 and February 2008 The study included 30 patients with clinical hypothyroidism, and 30 patients with sub- clinical hypothyroidism [21 of them were recruited before starting the treatment]. Also, the study included 30 patients with clinical hyperthyroidism, 30 with sub-clinical hyperthyroidism, [37 of them were recruited before starting the treatment] and 30 normal individuals as the control group. Prothrombin time [PT], activated partial thromboplastin time, fibrinogen level, and platelets count were performed in patients and control samples. A significantly decrease in PT was observed in hypothyroid patients, and hyperthyroid patients compared to the control group. Activated thromboplastin time was significantly decreased only in hyperthyroid patients, compared to the control group. Moreover, fibrinogen level was significantly increased in hyperthyroid patients compared to hypothyroid patients. The study concluded that minor coagulation abnormalities were observed in both subclinical hypo- and hyperthyroidism compared to clinical hypo- and hyperthyroidism. Platelets count was also slightly decreased in both types of the disease. There was no significant effect of the treatment and age of such patients on the measured parameters. The study recommended to screen female patients with hypo- and hyperthyroidism for coagulation defect, to avoid the risk of such complications