Thyroid dysfunctions and autoimmunity in breast cancer patients: a prospective case-control study

ABSTRACT Objective: The relationship of thyroid dysfunction and autoimmunity with breast cancer (BC) continues to be contentious. The primary aim of this study was to estimate the prevalence of thyroid dysfunctions and autoimmunity in BC patients, and the secondary aims were to investigate the relationship of thyroid dysfunction with the clinicopathological profile of and therapy received by BC patients. Materials and methods: This was a single-center prospective case-control study (March 2015-May 2017). Women with BC (n = 191), age-matched healthy controls (n = 166) and malignant controls (patients with cervical cancer, n = 87) were enrolled. Basal serum free thyroxin (fT4), thyrotropin (TSH) and anti-thyroid peroxidase (TPO) antibody levels were measured in all three groups; fT4, TSH and TPO measures were repeated after chemotherapy and at the 1-year follow-up (one year after diagnosis) in the BC patients. Results: The prevalence of overall hypothyroidism and autoimmunity (p = 0.106) did not differ significantly between the three groups, but the rate of clinical hypothyroidism was significantly higher in the BC group than in the healthy control group and the malignant control group (12.2% vs. 3.0% vs. 4.6%, respectively; p = 0.001). BC patients had significantly lower mean basal TSH concentrations than the healthy controls (p = 0.017). The postchemotherapy TSH concentrations were significantly lower (p = 0.001), and the fT4 concentrations were higher, albeit not significantly (p = 1.00), than the respective basal concentrations. The reverse was true for the follow-up values, in which the TSH (p = 1.00) values were higher and the fT4 (p = 0.03) concentrations were lower than the respective basal concentrations. An additional 6% of the BC patients developed clinical hypothyroidism during follow-up. Hypothyroid (p = 0.02) and TPO-positive (p = 0.004) patients had significantly smaller tumors, but their other clinicopathological features were comparable to those without thyroid dysfunction. Conclusions: The prevalence of clinical hypothyroidism requiring thyroxine replacement was significantly high in BC patients and increased further during follow-up. Hence, BC patients should be considered a high-risk group that should receive routine screening for hypothyroidism.

Association between iron deficiency and prevalence of thyroid autoimmunity in pregnant and non-pregnant women of childbearing age: a cross-sectional study / 中华医学杂志(英文版)

Background@#Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age.@*Methods@#Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women’s data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 μg/L and iron overload (IO) was defined as ferritin >150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders.@*Results@#The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ2 = 10.264, P = 0.002; 6.25% vs. 3.70%, χ2 = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011–3.282, P = 0.046, respectively).@*Conclusion@#ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.@*Clinical trial registration@#ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

Endotelina-1, proteína C reactiva ultrasensible y actividad antioxidante en pacientes con hipotiroidismo subclínico y en eutiroideos con autoinmunidad tiroidea. Efectos del tratamiento con levotiroxina / Endothelin-1, high sensitivity C reactive protein and antioxidant activity in subclinical hypothyroid patients. Effects of levothyroxine treatment

RESUMEN La Endotelina-1 (ET1) y Proteína C Reactiva ultrasensible (PCRus) como marcadores de disfunción endotelial (DE) e inflamación vascular en hipotiroidismo subclínico (HS) han mostrado resultados controvertidos. El rol del estrés oxidativo y defensa antioxidante (TRAP) es motivo de discusión. Objetivos Establecer si el HS y la autoinmunidad tiroidea (AIT), excluyendo otros factores de riesgo cardiovascular, pueden causar DE e inflamación vascular, evaluadas a través de ET1 y PCRus, respectivamente. Establecer si TRAP juega algún rol. Evaluar cambios en ET1 y PCRus luego del tratamiento con levotiroxina (LT4). Material y métodos Se evaluaron prospectivamente 70 pacientes divididos en 3 grupos: HS: 41 pacientes (T4 normal,TSH >4,2 y <10 mUI/L), AIT: 10 pacientes eutiroideos (TSH <4,2 mUI/L) con aTPO y/o aTg (+) y Control: 19 pacientes eutiroideos sin AIT. Se excluyeron otros factores de riesgo cardiovascular. Se midió basalmente ET1, PCRus y TRAP plasmáticos, y en HS bajo LT4 (n = 24): ET1 y PCRus. Resultados No hubo diferencias significativas en edad, IMC, perfil lipídico y TRAP. ET1 y PCRus fueron significativamente mayores en pacientes con HS (media ± DS 1,77 ± 0,85 pg/ml y 1,5 ± 0,6 mg/l vs. controles (0,8 ± 0,3 pg/ml y 0,5 ± 0,2 mg/l) p <0,0001 y <0,008 respectivamente. Del mismo modo en AIT (1,4 ± 0.4 pg/ml y 2,3 ± 1,3 mg/l) vs controles p <0,0001 y <0,034, respectivamente. La TSH fue mayor en el grupo AIT vs. Control 2,57 ± 0,88 vs. 1,64 ± 0,5 mUI/L; p = 0,002. En HS bajo LT4 (8,7 ± 3,8 meses) se observó descenso de ET1 (p <0,001). ET1 correlacionó con TSH (r = 0,5 p <0,0001). El punto de corte de ET1 mediante curva ROC fue 1,32 pg/ml (Sensibilidad 81,6%-Especificidad 75%). Conclusiones ET1 y PCRus resultaron marcadores útiles para evaluar DE e inflamación vascular asociadas a HS. La defensa antioxidante no ejercería un rol en estos mecanismos. El tratamiento con LT4 produjo una significativa caída de ET1, pudiendo necesitarse un período más largo de eutiroidismo para normalizarla. En AIT, niveles de TSH >2,5 mUI/L podrían sugerir un mínimo grado de hipotiroidismo justificando la elevación en ET1 y PCR, sin descartar el rol de la AIT "per se".

ABSTRACT The measurement of endothelin-1 (ET1) and high sensitivity C-reactive protein (hsCRP) as markers of endothelial dysfunction (ED) and vascular inflammation in subclinical hypothyroidism (SH) has shown controversial results. The role of oxidative stress and antioxidant defense (TRAP) is a matter of discussion. Objectives To establish if SH and thyroid autoimmunity (TAI), excluding other cardiovascular risk factors, may cause ED and vascular inflammation, evaluated through the measurement of ET1 and hsCRP respectively. To determine if TRAP could have some role. Additionally, changes in these parameters after treatment with levothyroxine (LT4) will be evaluated. Material and methods: 70 patients were prospectively evaluated. They were classified into: SH Group: 41 patients (normal T4, TSH> 4.2 and <10 mIU/L), TAI Group: 10 euthyroid patients (TSH <4.2 mUI/L) with positive aTPO and/or aTg and Control Group: 19 euthyroid patients without TAI. Other cardiovascular risk factors were excluded in patients and controls. Plasma ET1, hsCRP and TRAP were measured basally, and ET1 and hsCRP under LT4 therapy in the HS Group. Results There were no significant differences between the 3 groups in age, BMI, lipids and TRAP. ET1 and hsCRP were significantly higher in patients with SH (mean ± SD 1.77 ± 0.85 pg/ml and 1.5 ± 0.6 mg/l) vs. controls (0.8 ± 0.3 pg/ml y 0.5 ± 0.2 mg/l) p <0.0001 y <0.008 respectively. Similarly, in TAI patients (1.4 ± 0.4 pg/ml y 2.3 ± 1.3 mg/l) vs controls, p <0.0001 and <0.034, respectively. TSH was higher in the TAI patients versus control group (2.5 ± 0.88 versus 1.64 ± 0.5 mIU/L, p = 0.002). Twenty-four patients with SH showed a significant decrease in ET1 (p <0.001) under treatment with LT4 (8.7 ± 3.8 months). ET1 had a highly significant correlation (p <0.0001) with TSH (r = 0.5). The cut-off level of ET1 established by ROC curve was 1.32 pg/ml (Sensitivity 81.6%-Specificity 75%). Conclusions ET1 and hsCRP were useful markers to evaluate ED and vascular inflammation associated with SH. There were no differences in TRAP levels between patients and controls, so it does not appear that oxidative stress would have played any role. Treatment with LT4 produced a significant drop in ET1. Probably, a longer period of euthyroidism might be necessary to normalize ET1 levels. In TAI Group, TSH levels >2.5 mUI/L could suggest a "minimal degree" of hypothyroidism justifying the elevation in ET1 and hs CRP. The role of the TAI "per se" couldn't be completely ruled out.

Learning from POSTAL study: can levothyroxine improve pregnancy outcomes in women with thyroid autoimmunity? / 中华内分泌代谢杂志

Whether levothyroxine ( LT4 ) treatment improves outcomes following in vitro fertilization and embryo transfer ( IVF-ET) in euthyroid women who have tested positive for thyroid autoantibodies remains unclear. In Pregnancy Outcome Study in enthyroid women with Thyroid Autoimmunity after Levothyroxine ( POSTAL) trial, which was a randomized controlled study involving 600 euthyroid women undergoing IVF-ET who were tested positive for thyroperoxidase antibodies, the miscarriage rate, clinical pregnancy rate and live-birth rate were not significantly different between the LT4 intervention group and control group. Therefore, LT4 treatment did not appear to improve pregnancy outcomes among women with thyroid autoantibodies undergoing IVF-ET.

THE STUDY OF FEMALE INFERTILITY WITH ANTI-TPO AND ANTI-TG AUTOIMMUNE DEFICIENCY IN THYROID GLAND / Шинэ санаа Шинэ нээлт

@#BACKGROUND. According to the World Health Organization (WHO), 10-15% of couples of reproductive age have infertility. According to researcher D. Sukhe (1999), hormonal infertility in the reproductive age of women was 33.6%, which was a large part of the cause of infertility. In recent years, the number of cases of endocrine disorders, including malignancy and sexually transmitted infections, have been increasing year by year. According to WHO reports, thyroid disorders have a prevalence of 49.3% among active reproductive age (30-50) group. According to the report of the Health Development Center in 2016, since the thyroid disorders are the second most common disease in endocrine gland disease, our study has found that the infertility in reproductive age of women can be substantial due to the loss of thyroid gland. OBJECTIVE. To study the relationship between the thyroid gland antibodies and female infertility. MATERIAL AND METHODS. The study was carried out in 20-45 year old couples and was modeled as an analytical study model. The questionnaire was used for the couple’s interviews, antroplogical measurements, and serum was analysed. On the serum, anti-TPO and аnti-TG carbohydrates were identified by the Cobas e-411 analyzer under the manufacturer’s accompanying protocol. RESULTS. Prevalence of TAI, in 6.7% positive anti-Tg were found, and 14.3% had positive TPO. In 3.7% of cases, both types of autoantibodies were present. We analysed binary logistic regression for anti-TPO and anti-TG autoantibody in the positive and negative group in relation to the past obstetrics history. A=Accoding to the analysis, evidence of positive anti-TPO and anti-Tg increased the risk of miscarriage by 2.2 times (OR = 2.2, p <0.01). CONCLUSION: Women with infertility in our study have high percentage of subclinical hypothyroidism and have higher rate of thyroid autobodies in serum which could be a problem for women with infertility and pregnancy complications due to the loss of thyroid gland. Thus, there is a need to develop intervention guidelines for recovery and treatment of these types of infertility.

THE STUDY OF FEMALE INFERTILITY WITH ANTI-TPO AND ANTI-TG AUTOIMMUNE DEFICIENCY IN THYROID GLAND / Шинэ санаа Шинэ нээлт

@#BACKGROUND: According to the World Health Organization (WHO), 10-15% of couples of reproductive age have infertility. According to researcher D. Sukhe (1999), hormonal infertility in the reproductive age of women was 33.6%, which was a large part of the cause of infertility. In recent years, the number of cases of endocrine disorders, including malignancy and sexually transmitted infections, has been increasing year by year. According to WHO reports, thyroid disorders have a prevalence of 49.3% for active reproductive age (30-50). According to the report of the Health Development Center in 2016, since the thyroid disorders are the second most common disease in endocrine gland disease, our study found that the infertility in reproductive age of women can be substantial due to the loss of thyroid gland. METHODS: The study was carried out by the couple of 20-45 year-olds and modeled as an analytical study model. The questionnaire was used for the couple’s interviews and some of the measurement of body and serum use of TOSOH Corporation AIA-360, Tokyo, Japan. On the serum, anti-TPO and аnti-TG carbohydrates are identified by the Cobas e-411 analyzer under the manufacturer’s accompanying protocol. RESULTS: 76.7% of women were diagnosed with infertility euthyroid, 0.7% hyperthyroidism, 22.6% hypothyroidism (3.8% with overt hypothyroidism and 18.8% subclinical hypothyroidism). Prevalence of TAI, in 6.7% isolated positive anti-Tg were found, and 14.3% had isolated positive TPO, In 3.7% of cases, both types of autoantibodies were present. We analysed binary logistic regression for anti-TPO and anti-TG autoantibody in the positive and negative group in past obstetrics history, evidence of positive of anti-TPO and anti-Tg was increased risk of miscarriage 2.2 times (OR = 2.2, p <0.01). CONCLUSIONS: Women with disorders in our study have high percentage of subclinical hypothyroidism and have higher rate of thyroid autobodies in serum which may be a problem for women with infertility and pregnancy complications due to the loss of thyroid gland. There is a need to develop a principle of recovery and treatment.

Related quality of life questionnaire specific to dysthyroid ophthalmopathy evaluated in a population of patients with Graves' disease

ABSTRACT Objective The aim of this study was to measure quality of life (QOL) impairment in individuals currently suffering from Graves' ophthalmopathy (GO) and to determine the correlation of GO-specific QOL scores with disease severity and activity. Subjects and methods Seventy three GO-specific QOL surveys were prospectively analysed and compared with GO status. The GO-specific QOL survey was translated into Spanish and applied to Argentine patients with Graves' disease (GD). Results were compared with presence or absence of GO, Clinical Activity Score (CAS), severity score, age, gender and thyroid function. Results Fifty-six patients answered the survey and underwent complete ophthalmic evaluation, 15 did not have GO and were considered to be a control group. Appearance QOL score for patients with GO (53 ± 31.4) was lower than the control group (88.3 ± 17) (p < 0,000), no difference was observed in functional QOL score. There was a negative correlation between GO severity and both functional (r = -0.575; p < 0.000) and appearance QOL (r = -0.577; p < 0.000). Functional QOL differed between patients with active GO vs control group (p = 0.043). Patients with active and inactive GO had lower appearance QOL scores than control group (p < 0.000, p < 0.001 respectively). Conclusions GO has significant impact on the life of these Argentine patients. QOL was worse in GO patients than in control group, functional QOL was mostly affected by the activity and appearance QOL was mainly altered by the effects of the disease. Patients with more severe GO had lower scores on both QOL scales.

Niveles de tirotrofina y anticuerpos antitiroperoxidasa en el primer trimestre de gestación asociados a complicaciones del embarazo en la mujer eutiroidea / Thyrotropin levels and anti-thyroid peroxidase antibodies during first trimester of pregnancy associated with maternal and foetal complications in euthyroid women

Introducción: El embarazo es una situación fisiológica que presenta cambios endócrinos e inmunológicos. La tiroides modifica su economía para proveer suficientes hormonas a la madre y al feto. La autoinmunidad y las disfunciones tiroideas tienen alta prevalencia en mujeres en edad fértil y pueden afectar el curso de la gestación, con repercusiones clínicas adversas maternas y fetales. El objetivo de este estudio fue relacionar la proporción de gestantes eutiroideas con tirotrofina (TSH) en 2 niveles del rango de referencia ( ± DS; 1,57 ± 0,82 vs. 1,16 ± 0,54 mUI/l, p = 0,001). Los niveles séricos de T4L y T4 fueron similares en ambos grupos. De la subpoblación EP, el 63% fue incluida en EP1 y el 37% en EP2, y en EN el 80% en EN1 y el 20% en EN2. Se observó un incremento significativo (p = 0,001) en las complicaciones en EP (22%) vs. EN (10%). En mujeres EP con y sin aborto espontáneo, la TSH ( ± DS) fue 1,65 ± 0,67 vs. 0,99± 0,77 mUI/l (p = 0, 014). Las mujeres EP con y sin parto prematuro presentaron niveles de TSH (X ± DS) 1,63 ± 0,70 vs. 1,15 ± 0,53 mUI/l (p = 0,012). En el grupo EN, el nivel de TSH ( ± DS) para las mujeres con y sin aborto fue 1,45 ± 0,61 vs. 0,85± 0,66 mUI/l (p = 0,001), mientras que en mujeres con y sin parto prematuro la TSH ( ± DS) fue 1,59 ± 0,71 vs. 0,83 ± 0,64 mUI/l (p = 0,001), respectivamente. Sin embargo, no hubo diferencias entre los niveles promedio de TSH encontrados en aborto vs. parto pretérmino en ambos grupos. En EP, 32 mujeres y 19 en EN desarrollaron hipotiroidismo en el curso del embarazo (ns) y 29 en EP y 10 en EN tiroiditis posparto (p = 0,005). La autoinmunidad tiroidea y los mayores niveles de TSH dentro del rango de referencia en mujeres en primer trimestre de embarazo estarían asociados a complicaciones en el transcurso de la gestación y desarrollo de disfunción tiroidea posparto.

Introduction: Pregnancy is a physiological state presenting with endocrine and immunological changes. The thyroid gland modifies its output in order to provide enough hormonesto the mother and foetus. Thyroid autoimmunity and thyroid dysfunction are prevalent in women of childbearing age and may affect the course of gestation and having maternal and foetal clinical consequences. The purpose of the present study was to establish the relationship between euthyroid pregnant women with thyrotropin (TSH) at two levels of the reference range ( ± SD; 1.57 ± 0.82 vs 1.16 ± 0.54 mIU/L, P=.01). FT4 and T4 values were similar in both groups. Out of the pregnant women in the EP group, 63% were included in EP1, and 37% in EP2. In the EN group, 80% of women were included in EN1 and 20% in EN2. A significant (P=.001) increase in pregnancy complications in EP group (22%) vs EN (10%) was observed. In the EP group, TSH levels were: 1.65 ± 0.67 vs 0.99± 0.77 ( ± SD) mIU/L (P=.014) respectively, in women with and without miscarriage. TSH levels were 1.63 ± 0.70 vs 1.15 ± 0.53 ( ± SD) mIU/L (P=.012), respectively, in women with and without preterm delivery. In the EN group TSH levels were: 1.45 ± 0.61 vs 0.85± 0.66 ( ± SD) mIU/L (P=.001), respectively, in women with and without miscarriage. TSH levels were 1.59 ± 0.71 vs 0.83 ± 0.64 ( ± SD) mIU/L (P=.001), respectively, in women with and without preterm delivery. However, TSH levels in miscarriage and preterm delivery were similar. Thirty-two EP, and 19 EN women developed hypothyroidism in pregnancy (ns), and 29 EP and 10 EN women developed post-partum thyroiditis (P=.005). Conclusion: Thyroid autoimmunity and higher TSH levels within the reference range during the first trimester of pregnancy were associated with pregnancy complications and with the development of thyroid postpartum dysfunction.

Serum vitamin D3 levels are not associated with thyroid cancer prevalence in euthyroid subjects without autoimmune thyroid disease

BACKGROUND/AIMS: Previous studies have suggested that elevated serum vitamin D levels might protect against thyroid cancer. Elevated serum thyroid stimulating hormone levels and autoimmune thyroid disease (AITD) are suggested to be thyroid cancer promoting factors but have not been well controlled in previous studies. We designed the present study to evaluate whether serum vitamin D levels are associated with thyroid cancer in euthyroid patients with no clinical evidence of AITD. METHODS: This cross-sectional study included subjects who underwent routine health check-ups, including serum 25-hydroxy vitamin D3 (25(OH)D3) levels, anti-thyroid peroxidase antibody (TPO-Ab), and thyroid ultrasonography (US). Inclusion criteria were euthyroid, negative TPO-Ab, and no evidence of AITD by US findings. Thyroid cancer diagnoses were based on fine needle aspiration cytology and/or postsurgical histopathological findings. RESULTS: We enrolled 5,186 subjects (64% male, 37% female) in this study, including 53 patients (1%) with a diagnosis of thyroid cancer (33 males, 20 females). Mean 25(OH)D3 levels were similar between the thyroid cancer and control groups (p = 0.20). Subgroup analysis according to sex or seasonal variation also revealed no differences in 25(OH)D3 levels between the two groups. Based on the levels of 25(OH)D3, there was no significant difference in the prevalence of thyroid cancer; the prevalence was 0.71%, 0.94%, 1.40%, and 0.82% in the deficient, insufficient, sufficient, and excess groups, respectively (p = 0.64). CONCLUSIONS: The levels of serum 25(OH)D3 are not associated with thyroid cancer prevalence in euthyroid subjects with no clinical evidence of AITD.

Prevalencia de enfermedades tiroideas en una población del área metropolitana de Buenos Aires / Prevalence of thyroid diseases in a population of the metropolitan area of Buenos Aires

La prevalencia de alteraciones morfológicas palpables tiroideas no supera el 8% en la población adulta. En el Hospital de Clínicas de la Universidad de Buenos Aires se llevó a cabo un programa gratuito para la detección de enfermedades tiroideas, convocándose a sujetos que desconocieran antecedentes tiroideos. Nuestro objetivo fue establecer la frecuencia de patología morfológica palpable tiroidea, en una población seleccionada de pacientes, y comparar dichos resultados con los hallazgos de un programa de detección similar, realizado en el año 2001¹. Adicionalmente, evaluar la prevalencia de alteraciones funcionales y de autoinmunidad tiroidea. Los individuos que concurrieron se dividieron en 3 grupos: Grupo 1 (n = 186) pacientes con antecedentes personales de enfermedad tiroidea conocida (excluidos del análisis); Grupo 2 (n = 184) sujetos con antecedentes familiares, otras enfermedades autoinmunes, o sintomatología que pudiera atribuirse a alteración de la función tiroidea (grupo inducido), y Grupo 3 (n = 288) sujetos que consultaron por mera curiosidad (grupo random). La función y autoinmunidad tiroidea se evaluó en 144 participantes del Grupo 3, citados al azar. En el grupo random, la prevalencia de alteraciones morfológicas tiroideas, detectadas por palpación, fue del 11,09%. Al comparar estos resultados con los obtenidos 12 años atrás en un estudio similar, realizado en nuestro hospital, no se encontraron diferencias estadísticamente significativas (8,7 vs. 11,09%; p = 0,25). En cuanto a la función tiroidea, se halló hipotiroidismo subclínico en el 6,25%, hipertiroidismo subclínico en el 0,7% y autoinmunidad en el 11% de los sujetos evaluados. En conclusión, la prevalencia de alteraciones palpables de la glándula tiroides no cambió en laúltima década. Esta investigación realizada en una población correctamente seleccionada constituye una herramienta útil para referencias futuras como población control en Argentina.

The prevalence of palpable thyroid morphological abnormalities does not exceed 8% in the adult population. A free program was conducted in the Hospital de Clínicas (University of Buenos Aires) for the detection of thyroid diseases, inviting subjects who were unaware of a history of these diseases. The aim was to establish the frequency of goitre in the selected population, as well as to evaluate the prevalence of functional disorders and thyroid autoimmunity, and to compare these results with the findings of a similar study performed in 2001¹. The subjects were divided into three groups: Group 1 (n = 186) patients with a history of previously known thyroid disorders (excluded subjects); Group 2 (n = 184) subjects with a family history of thyroid disease, other autoimmune diseases, or symptoms that could be attributed to changes in thyroid function (Induced Group), and Group 3 (n = 288) subjects who participated in this program due to mere curiosity (Random Group). Autoimmunity and thyroid function was assessed in 144 randomly selected participants in Group 3. In Group 3, the prevalence of morphological alterations of the thyroid gland was 11.09%. Comparing these results with those obtained 12 years ago in a similar study performed in our hospital, no statistically significant differences were found when the prevalence of morphological thyroid alterations were compared (8.7% vs 11.09%, p=.25). As for thyroid function, subclinical hypothyroidism was found in 6.25%, subclinical hyperthyroidism in 0.7%, and autoimmunity in 11% of subjects evaluated. It was concluded that the prevalence of palpable thyroid abnormalities had not change in the last decade. This study, made in a correctly selected population, is a useful tool for future reference as a control population in Argentina.

Thyroid disorders and fertility.

Reproductive function is a vital process for continuation of life and requires an appropriate endocrine, molecular and cellular organization. In every stage starting from maturation of ovarian follicle up to implantation of the embryo, a convenient endocrine environment including normal thyroid hormone levels is of utmost importance. After the initial revelation of the correlation between reproductive health and thyroid functions in numerous studies have emphasized that both hyperthyroidism (OHT) and hypothyroidism (OH) are effective in female reproductive system, though varyingly. Our aim in this review is to evaluate effects of hyper- and hypothyroidism on fertility and also discuss relationship of infertility and assisted reproductive techniques (ART) regarding their effects over thyroid functions and auto-immunity under the guidance of current information.

Thyroid function, autoimmunity and nodules in hematological malignancies

Objective Hematological malignancies encompass a large spectrum of disease entities whose treatment by chemo/radiotherapy could lead to thyroid complications. To the best of our knowledge, no study has simultaneously addressed thyroid function, autoimmunity and nodularity. Therefore, we decided to conduct one.Materials and methods We evaluated 82 Caucasian patients (36 women and 46 men), who were treated at our Oncology division for hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphatic leukemia, non-Hodgkin lymphoma and polycythemia vera) and compared them with a control group of 104 patients. Patients who had received or were receiving external head/neck radiotherapy were excluded. All oncological patients and control individuals underwent thyroid ultrasonography and thyroid function and autoimmunity tests.Results A lower prevalence of enlarged thyroid and nodules were found in patients with respect to controls. The rate of thyroid nodules was the highest in multiple myeloma and polycythemia vera, and the lowest in chronic lymphatic leukemia. Non-Hodgkin lymphoma patients had the smallest thyroid nodules while men with multiple myeloma the biggest ones. No patient had hypothyroidism, while 5.6% of patients had subclinical hyperthyroidism. In contrast, within the control group the rates of hypothyroidism and hyperthyroidism, overt and subclinical, were 3.8%, 20.2%, 0% and 0% respectively. Moreover, the overall rate of thyroid autoantibody positiveness in patients was significantly lower than controls.Conclusion In our experience, we found a significantly lower prevalence of thyroid abnormalities in hematologic patients who underwent chemotherapy, but not radiotherapy, with respect to controls. Arch Endocrinol Metab. 2015;59(3):236-44.

Prevalencia de tiroideopatías en pacientes con diabetes tipo 2 / Prevalence of Thyroid Disease in Patients with Type 2 Diabetes

Objetivo: Determinar la frecuencia de bocio, disfunción y autoinmunidad tiroidea en una muestra poblacional de pacientes con diabetes tipo 2. Material y métodos: Se analizaron pacientes con diagnóstico de diabetes tipo 2, según los criterios de la American Diabetes Association 2007, asistidos en forma consecutiva en consultorios de endocrinología, desde el 1 de julio al 31 de octubre de 2011. Resultados: Se recabaron datos de 190 pacientes, promedio de edad de 61,7 años (rango 27-85), 103 eran mujeres (54,2 %). Se determinaron anticuerpos antitiroideos en 139 pacientes. Ciento tres (54,2 %) pacientes presentaban disfunción tiroidea, 84 (44,2 %) ya tenían diagnóstico previo y se detectaron 19 (10,0 %) nuevos casos a partir del estudio. El hipotiroidismo clínico fue la disfunción tiroidea más frecuente (68 pacientes [35,8 %]). Cincuenta y dos pacientes presentaban bocio (27,4 %), la mayoría multinodular (36 pacientes [18,9 %]). Treinta y dos pacientes tenían autoinmunidad positiva (23,0 %). No se observaron diferencias significativas al dividir los pacientes en mayores y menores de 65 años respecto a la frecuencia de disfunción tiroidea (57,8 % contra 51,0 %) ni respecto a la de bocio (25,6 % contra 29 %). En cambio, fue significativa la diferencia en la proporción de autoinmunidad positiva entre ambos grupos (13,1 % y 30,8 %) (P < 0,05). Se halló un porcen­taje en mujeres y varones de disfunción tiroidea de 70,8 % y 34,5 % (P <0,0001), de bocio en 41,7 % y 10,3 % (P < 0,0001) y de anticuerpos antitiroideos positivos de 27,9 % y 15,1 % (P no significativa), respectivamente. Conclusiones: Se observó una frecuencia de disfunción tiroidea de 54,2 %, mayor que en todos los estudios revisados. La importancia de detectar tiroideopatías en los diabéticos tipo 2 radica en el diagnóstico de una patología tratable y que puede contribuir al aumento del riesgo cardiovascular de estos pacientes. Rev Argent Endocrinol Metab 51:123-129, 2014 Los autores declaran no poseer conflictos de interés.

Aim: To assess the frequency of goiter, thyroid dysfunction and autoimmunity in a group of patients with type 2 diabetes. Material and Methods: We evaluated a group of patients with diagnosis of type 2 diabetes, who presented at the Endocrinology department from July 1st to October 31st, 2011. The diagnosis of diabetes was based on the American Diabetes Association criteria. Results: Data from 190 patients were analyzed. The mean age was 61.7 years (range 27-85); 103 were women (54.2%). Thyroid autoantibody measurements were available in 139 patients. The total frequency of thyroid dysfunction was 54.2 % (103 patients), 84 patients (44.2 %) with previous diagnosis and 19 patients (10.0 %) with new diagnosis. The most frequent thyroid dysfunction was overt hypothyroidism (68 patients [35.8 %]). Goiter was present in 52 patients (27.4 %), most of them had multinodular goiter (36 patients [18.9 %]). Thy­roid autoantibodies were positive in 32 patients (23.0 %). We classified patients into two groups according to age: patients over 65 (group 1) and patients under 65 (group 2). No significant difference in the frequency of thyroid dysfunction (57.8 % versus 51.0 %) and goiter (25.6 % versus 29.0 %) were found between these groups. However, there was a significant difference in the proportion of thyroid autoimmunity according to age (13.1 % and 30.8 %, P <0.05, respectively). When separating patients into women and men, the percentage of thyroid dysfunction was 70.8 % and 34.0 % (P <0.0001), the percentage of goiter was 41.7 % and 10.3 % (P <0.0001) and the percentage of thyroid autoimmunity was 27.9 % and 15.1 % (not statistically significant), respectively. Conclusions: The frequency of thyroid dysfunction was 54.2 %, which was the highest rate according to the studies reviewed. Detection of thyroid dysfunction in patients with type 2 diabetes is clinically important since it is a treatable disease that may contribute to an increased cardiovascular risk in these patients. Rev Argent Endocrinol Metab 51:123-129, 2014 No financial conflicts of interest exist.

Analysis of the clinicopathological characteristics of differentiated thyroid carcinoma in women / 中国肿瘤临床

Objective:We aimed to analyze the clinicopathological characteristics of differentiated thyroid carcinoma (DTC) in women. Methods:The clinical data of 1,034 female patients with thyroid nodules between January 2003 and December 2012 were retrospectively analyzed. These patients were from Yunnan Province, China. A database was established in Excel. Univariate and multivariate conditional logistic regression analyses were conducted by using SPSS 17.0. Results:Female patients with DTC were younger than those with thyroid nodule disease or benign thyroid disease (BTD). The results of univariate conditional logistic regression analysis showed that the preoperative mean level of serum thyrotropin was higher in patients with DTC than in patients with BTD (P=0.034). The positive ratios of thyroid peroxidase antibody, thyroglobulin antibody (TGAb), and thyrotrophin receptor antibody (TRAb) were higher in patients with DTC than in patients with BTD (P<0.001). The positive ratio of the coexistence of DTC with Hashimoto's thyroiditis (HT;13.3%) or with lymphocytic thyroiditis (LT;4.2%) was higher in patients with DTC than in patients with BTD and HT/LT (P<0.001). The ratio of the patients whose age of menarche was≤13 years, with≤2 of births, or were in pre-menopausal condition in the DTC group was higher than that in the BTD group. The results of multivariate conditional logistic regression analysis showed that age<45 years, nodal size<1 cm, and thyroglobulin increase were protective factors of DTC with odds ratios (ORs) of 0.06, 0.377, and 0.431, respectively. An abnormal increase in TGAb and TRAb was an independent risk factor of female patients with DTC with ORs of 4.949 and 23.001, respectively. Conclusion:Female patients aged 35 years to 44 years and with thyroid nodules were included in a high-risk group of DTC. Serous thyroid-stimulating hormone 1evel and coexistence with HT were positively correlated with the risk of DTC in females. Early menarche, late menopause, and low number of births were associated with the incidence of DTC in females. Age<45 years, nodal diameter<1 cm, and increase in thyroglobulin were protective factors of DTC in female. An abnormal increase in TGAb and TRAb was an independent risk factor of female DTC.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Autoinmunidad tiroidea: Mecanismos patogénicos comunes y distintivos en tiroiditis de Hashimoto y enfermedad de Graves / Thyroid Autoimmunity: Common and Distinctive Pathogenic Mechanisms in Hashimoto's Thyroiditis and Graves' Disease

Las enfermedades tiroideas autoinmunes (ETA) son los desórdenes más frecuentes que llevan a la disfunción de la glándula tiroidea. Incluyen varias formas clínicas como Tiroiditis de Hashimoto (TH) y Enfermedad de Graves (EG). La relación entre TH y EG ha sido objeto de debate por décadas. Si bien, muy diferentes en su clínica, algunos las consideran los lados opuestos de una misma moneda. En su patogénesis tienen aspectos en común, como la predisposición genética demostrado por la ocurrencia en una misma familia y en un mismo individuo. Sin embargo, diferencias en el microambiente local determinan la diferente expresión fenotípica o el viraje de una a otra patología. El objetivo de esta monografía es investigar similitudes y diferencias entre TH y EG en las distintas etapas que llevan al desarrollo de autoinmunidad. Los autores declaran no poseer conflictos de interés.

Autoimmune thyroid disease (ATD) is the most common disorder that leads to thyroid gland dysfunction. ATD manifests in various clinical forms, such as Hashimoto's Thyroiditis (HT) and Graves' Disease (GD). The relation between HT and GD has been discussed for decades. Even if they greatly differ in their clinical features and treatment, some people believe they are the opposite sides of the same coin. In their pathogenesis, they share some mechanisms, such as genetic susceptibility, shown by the fact that they tend to occur both in the same person and within the same family. However, differences in the local micro-environment can determine the distinct phenotypic expression or the switch from one disease to the other. The aim of this monograph was to investigate similarities and differences between HT and GD at the diverse stages leading to the development of autoimmunity. No financial conflicts of interest exist.

Prevalence of undiagnosed autoimmune thyroid disease and thyroid dysfunction in Filipino patients with autoimmune rheumatic disorders / Journal of the ASEAN Federation of Endocrine Societies

OBJECTIVES:(1) To determine the prevalence of autoimmune thyroid disease among patients with autoimmune rheumatic disorders seen at the Philippine General Hospital. (2) To determine clinical features that are associated with the occurrence of autoimmune thyroid disease in these patient.METHODOLOGY:This is a cross sectional analytical study that included 155 adult Filipinos diagnosed with an autoimmune rheumatic disorder. Clinical characteristics were recorded. Serum thyrotropin, thyroxine, triiodothyronine, anti-thyroid peroxidase antibody, anti-thyroglobulin antibody and urinary iodide excretion were determined. The prevalence of autoimmune thyroid disease was computed. Associations between clinical factors and autoimmune thyroid disease were determined.RESULTS:Overall 21.94% of the population had autoimmune thyroid disease. There was significant association between duration of the autoimmune rheumatic disorder and autoimmune thyroid disease (p-= 0.018). No significant association was noted with the other clinical factors although there was an almost significant association observed for the presence of goiter (p=0.054).CONCLUSION:Autoimmune thyroid disease commonly occurs in patients with autoimmune rheumatic disorders. As such, it is important to consider screening these patients for the coexistence of thyroid disease to help prevent the complications associated with thyroid dysfunction and avoid adding up to the morbidity of the existing autoimmune rheumatic disorder.

Genetic Markers of Graves’ Disease: A Historical View and Up-date.

Two decades of intensive but quite chaotic and decentralized population studies on susceptibility to Graves’ disease (GD) provided a bulk of inconsistent data resulted in finding of proven association only for the HLA class II region that exerts a major effect in the genetics of GD. Using low-resolution microsatellite-based human genome-wide scans revealed several regions of linkage harboring putative susceptibility variants. Further, high throughput genotyping of large population cohorts with help of high dense panels of single nucleotide polymorphisms (SNPs) and application of advanced tools for analysis of extended blocks of linkage disequilibrium within a candidate gene (SNP tagging, etc.) revealed the presence of several susceptibility genes in the regions of linkage on chromosome 2q (CTLA-4), 8q (Tg), 14q (TSHR), 20q (CD40), 5q (SCGB3A2/UGRP1) and, probably, Xp (FOXP3). The list of GD-predisposing loci was then extended with three more genes (PTPN22, IL2RA/CD25, and FCRL3). In the nearest future, implementation of even more robust technology such as whole-genome sequencing is expected to catch any disease-associated genetic variation in the patient’s individual DNA. In this review, the historical development of our knowledge on genetic factors predisposing to GD is considered, with special emphasis on the functional significance of observed associations and discussion of possible mechanisms of their contribution to GD pathogenesis.

Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: A randomised, double-blind, placebo-controlled trial.

Background and objectives: The potential of soy isoflavones to interfere with thyroid function has been reported. However, there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women. The present study aimed to evaluate the effect of isoflavones on thyroid function and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH) and estradiol levels in oophorectomised women. Methods: A randomized, double blind, placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3 , free T4 , TSH, TBG and anti-TPO antibody titres) assessed at baseline, 6 and 12 wk after randomization. Assessment was also done for menopause symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at study completion. Results: There was a significant alteration in free T 3 levels in the group receiving isoflavones (4.05 ± 0.36, 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups. MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones (12.47 ± 8.15, 9.35 ± 5.23 and 9 ± 5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement in urogenital symptoms compared to placebo. Isoflavones did not significantly affect other parameters during study period. There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups. Interpretation and conclusions: Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant.

Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity.

Background & objectives: Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India. Methods: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T3, T4, TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium. Results: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P= 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 µg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 µg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group (P <0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 µg/l) as compared to controls (11, 6.4%; P<0.001). Serum ferritin level negatively correlated with the presence of goitre (r = - 0.22, P =0.008) and had an OR of 2.8 (CI 1.20 - 6.37, P =0.017). Interpretation & conclusions: There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.