Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Hipotiroidismo subclínico en el embarazo / Subclinical hypothyroidism in pregnancy

Las alteraciones de la función tiroidea incluida el hipotiroidismo subclínico son unas de las patologías más frecuentes durante el embarazo, y se asocian a importantes complicaciones maternas, fetales y neonatales. Se han desarrollado múltiples guías de práctica clínica por sociedades internacionales en busca de unificar el enfoque diagnóstico y terapéutico de las patologías tiroideas durante la gestación, sin embargo hay evidencia insuficiente sobre la realización de tamizaje y aún más sobre las intervenciones terapéuticas en caso del hipotiroidismo subclínico, se presenta la siguiente revisión de la literatura para vislumbrar a la luz de información actualizada como realizar el abordaje integral de las pacientes gestantes con hipotiroidismo subclínico (AU)

Alterations in thyroid function, including subclinical hypothyroidism, are one of the most frequent pathologies during pregnancy, and are associated with important maternal, fetal, and neonatal complications. Multiple clinical practice guidelines have been developed by international societies in search of unifying the diagnostic and therapeutic approach of thyroid pathologies during pregnancy, however there is insufficient evidence on screening and even more on therapeutic interventions in case of subclinical hypothyroidism , the following review of the literature is presented to envision in the light of updated information how to carry out a comprehensive approach to pregnant patients with subclinical hypothyroidism (AU)

Relationship of gender and age on thyroid hormone parameters in a large Chinese population

ABSTRACT Objective This study aimed to present the impact of age and gender on thyroid hormone levels in a large Chinese population with sufficient iodine intake. Subjects and methods A total of 83643 individuals were included and were stratified by age and gender. The median, 2.5th and 97.5th of thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and FT3/FT4 ratio were calculated for both genders for every decade from 18 to over 80 years. TSH, FT3, FT4, FT3/FT4 distribution in each age group was evaluated for females and males using smoothing splines in the generalized additive models (GAM). TSH concentrations were compared in the different age groups in gender. Results In the over 80s age group, the TSH level (median: 2.57 mIU/L, 2.5th-97.5th: 0.86-7.56 mIU/L) was significantly higher than other age groups, irrespective to gender (P<0.001). Females had a higher TSH value than males in all age groups (P<0.001). Results of the smoothing curves showed that TSH increased with age, FT3 concentration was higher in males than in females and the tendency of the FT3/FT4 ratio was basically similar to that of FT3. TSH concentration in the 50s age group (median 2.48 mIU/L for females versus 2.00 mIU/L for males) was significantly higher than that in the 30s age group (median 2.18 mIU/L for females versus median 1.85 mIU/L for males). Conclusions In accord with increasing TSH values during aging, females and older adults have lower FT3 values and lower FT3/FT4 ratios, while the FT4 values remain stable.

Anticuerpos anti-estreptavidina: Confusión diagnóstica por interferencia bioquímica / Anti-estreptavidin antibodies. Diagnostic confusion by biochemical interference

Se presenta el caso de una paciente que, durante los estudios por búsqueda de fertilidad y posterior embarazo, mostraba un perfil tiroideo alterado con niveles elevados de T4 libre y TSH normal. Luego de descartar un adenoma tirotropo y ante la ausencia de sintomatología clínica de hipertiroidismo, se investigó la posibilidad de interferencias analíticas en los inmunoensayos utilizados para la medición de las hormonas. Se han descrito interferencias causadas por anticuerpos heterófilos, macro TSH, anticuerpos anti-tiroideos, biotina, y en menor medida anticuerpos anti-estreptavidina y anti-rutenio. Los análisis de la paciente se realizaron en autoanalizador cuya plataforma emplea el sistema estreptavidina-biotina que es muy susceptible a varios interferentes. Un algoritmo propuesto incluye una serie de pruebas simples de realizar e interpretar que permiten detectar o descartar la presencia de interferentes. De acuerdo al mismo, se efectuó la comparación con una plataforma analítica diferente (que no utiliza el sistema estreptavidina-biotina), diluciones seriadas, precipitación con polietilenglicol 6000 y tratamiento con micropartículas recubiertas con estreptavidina. Los resultados obtenidos confirmaron la presencia de anticuerpos anti-estreptavidina en el suero de la paciente. Ante discordancias entre las manifestaciones clínicas y los resultados de laboratorio, se debe investigar la posibilidad de interferencias metodológicas para evitar el riesgo iatrogénico potencial que implica una interpretación bioquímica errónea.

We present the case of a patient who, during studies for fertility and subsequent pregnancy, showed an altered thyroid profile with elevated levels of free T4 and normal TSH. After ruling out a thyrotropic adenoma and in the absence of clinical symptoms of hyperthyroidism, the possibility of analytical interference in the immunoassays used to measure hormones was investigated. Interferences caused by heterophile antibodies, macro TSH, anti-thyroid antibodies, biotin, and to a lesser extent anti-streptavidin and anti-ruthenium antibodies have been described. The analysis of the patient was carried out in a self-analyzer whose platform uses the streptavidin-biotin system that is very susceptible to several interferents. A proposed algorithm includes a series of simple tests to perform and interpret that allow detecting or ruling out the presence of interferents. Accordingly, a comparison was made with a different analytical platform (which does not use the streptavidin-biotin system), serial dilutions, precipitation with polyethylene glycol 6000 and treatment with microparticles coated with streptavidin. Results obtained confirmed the presence of anti-streptavidin antibodies in the patient's serum. In the case of disagreements between clinical manifestations and laboratory results, the possibility of methodological interferences should be investigated in order to avoid the potential iatrogenic risk involved in an erroneous biochemical interpretation.

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.

Stress-induced hashitoxicosis: case report and relative HLA serotype and genotype

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.

RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Conversion to Graves disease from Hashimoto thyroiditis: a study of 24 patients

ABSTRACT Objective: The conversion of Hashimoto's thyroiditis (HT) to hyperthyroidism due to thyrotropin receptor antibodies is intriguing and considered rare. The contribution of TSH receptor blocking antibodies (TRAb), which may be stimulators (TSAb) or blockers (TBAb), is suspected. We describe clinical and biological variables in a series of patients switching from Hashimoto's thyroiditis to Grave's disease. Subjects and methods: Retrospective case study of 24 patients with Hashimoto's thyroiditis followed during 48 ± 36 months that developed later Graves' disease (GD). These variables were analysed in the hypo and hyperthyroid phase: age, sex, initial TSH, free triiodothyronine (fT3), free thyroxine (fT4), anti-TPO, TBII antibodies, parietal cell autoantibodies, time between hypo and hyperthyroidism, thyroid volume and levothyroxine doses (LT). Results: In HT, mean TSH was 9.4 ± 26.1 UI/L and levothyroxine treatment was 66.2 ± 30.8 µg/day. The switch to GD was observed 38 ± 45 months after HT diagnosis. As expected, we found significant differences on TSH, FT3, FT4 and TBAb levels. Three out of 14 patients had parietal cell autoantibodies. In two of these three cases there was an Helicobacter pylori infection. There were no significant differences between HT and GD groups with respect to thyroid volume. Conclusions: To our knowledge, large series documenting the conversion of HT to GD are scarce. Although rare, this phenomenon should not be misdiagnosed. Suspicion should be raised whenever thyroxine posology must be tapered down during the follow-up of HT patients. Further immunological and genetic studies are needed to explain this unusual autoimmune change.

Heart rate response to graded exercise test of elderly subjects in different ranges of TSH levels

ABSTRACT Objective: Life expectancy is increasing worldwide and studies have been demonstrating that elevated serum thyroid stimulating hormone (TSH) concentration in elderly is associated with some better health outcomes. This elevation is somewhat physiological as aging. The aim of this study was to investigate the heart rate (HR) response during a graded exercise test and its recovery in healthy elderly, comparing subjects within serum TSH in the lower limit of reference range to those within the TSH in the upper limit. Subjects and methods: A cross-sectional study was conducted with 86 healthy elderly aged 71.5 ± 5.1 years, with serum TSH between 0.4 - 4.0 mUl/mL. The participants were divided into two groups according to TSH level: < 1.0 mUl/mL (n = 13) and ≥ 1.0 µUI/mL (n = 73). All participants performed an ergometric test on a treadmill. The HR was recorded and analyzed at rest, during exercise and during the three minutes immediately after exercise. Results: No differences were observed in relation to HR at peak of exercise (TSH < 1.0 µUI/mL: 133.9 ± 22.5 bpm vs. TSH ≥ 1.0 µUI/mL: 132.4 ± 21.3 bpm; p = 0.70) and during the first minute of recovery phase (TSH < 1.0 µUI/mL: 122.3 ± 23.1 bpm vs. TSH ≥ 1.0 µUI/mL: 115.7 ± 18.4 bpm p = 0.33). The groups also presented similar chronotropic index (TSH < 1.0 µUI/mL: 78.1 ± 30.6 vs. TSH ≥ 1.0 µUI/mL: 79.5 ± 26.4; p = 0.74). Conclusion: In this sample studied, there were no difference between lower and upper TSH level concerning HR response during rest, peak of exercise and exercise recovery.

Higher prevalence of permanent congenital hypothyroidism in the Southwest of Iran mostly caused by dyshormonogenesis: a five-year follow-up study

ABSTRACT Objective: The incidence of congenital hypothyroidism (CH) varies globally. This 5-year study aimed to determine the prevalence of permanent CH in the southwest of Iran. Materials and methods: Between January 2007 and December 2009, all newborns in Ahvaz, the biggest city in the southwest of Iran, were screened for CH using a heel-prick sample for thyrotropin (TSH) levels. Subjects with TSH ≥ 5 mU/L were evaluated for T4-TSH. Infants with T4 < 6.5 µg/dL, TSH > 10 mU/L, and normal T4 but persistent (> 60 days) high TSH were considered to have CH. After the third birthday, treatment was discontinued, and T4-TSH was reevaluated; subjects with TSH ≥ 10 mU/L were investigated using thyroid Tc99 scintigraphy (TS). Based on TS, they were classified as normal, dysgenetic, or athyretic (agenesis). Results: Screening was performed for 86,567 neonates, and 194 were confirmed to have CH (100 males; F/M = 0.94; overall incidence 1:446). After the third birthday, reevaluation was performed in all (except 18 that were not accessible). From 176 patients, 81 (46%) were diagnosed with permanent CH, and 95 were discharged as transient. Considering the same percentage in the lost cases, the prevalence of permanent CH was found to be 1:970. TS performed for 53 of the permanent subjects found agenesis/dysgenesis in 25 (F:M = 15:10) and a normal result in 28 (F:M = 11:17), indicating dyshormonogenesis as the cause in more than 50% of subjects. Conclusions: The incidence of CH in this area was found to be higher than that in other countries but less than the incidence rate reported in central Iran. The large number of transient cases of CH suggests environmental or maternal causes for the incidence rather than a genetic basis.

Exercise training improves quality of life in women with subclinical hypothyroidism: a randomized clinical trial

ABSTRACT Objective: The aim was to evaluate the quality of life (HRQoL) in women with subclinical hypothyroidism (sHT) after 16 weeks of endurance training. Subjects and methods: In the first phase, a cross-sectional study was conducted in which 22 women with sHT (median age: 41.5 (interquartile range: 175) years, body mass index: 26.2 (8.7) kg/m2, thyroid stimulating hormone > 4.94 mIU/L and free thyroxine between 0.8 and 1.3 ng/dL were compared to a group of 33 euthyroid women concerned to HRQoL. In the second phase, a randomized clinical trial was conducted where only women with sHT were randomly divided into two groups: sHT-Tr (n = 10) - participants that performed an exercise program - and sHT-Sed (n = 10) - controls. Exercise training consisted of 60 minutes of aerobic activities (bike and treadmill), three times a week, for 16 weeks. The HRQoL was assessed by the SF-36 questionnaire in the early and at the end of four months. Results: Women with sHT had lower scores on functional capacity domain in relation to the euthyroid ones (770 ± 23.0 vs. 88.8 ± 14.6; p = 0.020). The sHT-Tr group improved functional capacity, general health, emotional aspects, mental and physical component of HRQoL after training period, while the sHT-Sed group showed no significant changes. Conclusion: After 16 weeks of aerobic exercise training, there were remarkable improvements in HRQoL in women with sHT.

Association of serum thyrotropin levels with coronary artery disease documented by quantitative coronary angiography: a transversal study

ABSTRACT Objective: The association between coronary artery disease (CAD) and thyroid function remains controversial. We evaluated the thyroid function and graduated well-defined CAD as confirmed by quantitative coronary angiography (CA). Subjects and methods: We evaluated the serum TSH, free thyroxine, free triiodothyronine and thyroid antibody levels in 300 consecutive patients (age 61.6 ± 9.9 years and 54% were male) undergoing CAD diagnosis as confirmed by CA. Plaques with ≥ 50% stenosis being indicative of obstructive CAD, and patients were divided into groups according to main epicardial coronary arteries with plaques (0, 1, 2, 3). Lipid profiles and a homeostasis model assessment (HOMA-IR) were determined. Results: Serum median (25% and 75% percentile) TSH levels in patients with group 2 and 3 (2.25; 1.66-3.12 mU/L and 4.99; 4.38-23.60 mU/L, respectively) had significantly higher TSH concentrations (p < 0.0001) than the group 0 (1.82; 1.35-2.51 mU/L). Furthermore, patients of group 3 had higher TSH concentration (p < 0.0001) than those of group 1 (1.60; 0.89-2.68 mU/L). Group 3 were older (64 ± 8.5 vs. 59 ± 9.5, p = 0.001), had more patients with dyslipidemia (84% versus 58%, p < 0.001), male (54% versus 44%, p = 0.01), hypertension (100% versus 86%, p < 0.001), and smoking (61% versus 33%, p < 0.001) than group 0. Multivariate stepwise logistic analysis showed TSH, age, HbA1c, and HOMA-IR were the CAD associated variables. Conclusions: In this cohort, elevated TSH levels in the high normal range or above are associated with the presence and severity of CAD besides may represent a weak CAD risk factor.

The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism

ABSTRACT Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (762 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs. −20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 762 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs. −19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r = −0.15, p < 0.05), E/A (r = −0.14, p < 0.05), GLS (r = −0.26, p < 0.001), and S/TDI (r = −0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

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.

Niveles de hormonas tiroideas en recién nacidos muy prematuros y prematuros extremos / Thyroid hormone Levels in very preterm neonates and extremely preterm

INTRODUCCIÓN: La función tiroidea del prematuro se ve alterada por la relativa inmadurez del eje hipotálamo-hipófisis-tiroides, junto a otros factores como la incidencia de enfermedades o el uso de algunos fármacos. Actualmente existe controversia sobre los niveles normales de tiroxina libre (T4L) en recién nacidos prematuros. Nuestro objetivo fue determinar la distribución de los valores de hormonas T4L y TSH, en recién nacidos menores de 32 semanas o 1.500g de peso al nacer, a los 15 días de edad cronológica, en el servicio de neonatología Hospital Dr. Hernán Henríquez Aravena, Temuco. Pacientes y MÉTODO: Estudio de corte trasversal, se analizaron los resultados de T4L y TSH desde una base de datos a 308 recién nacidos, los que fueron categorizados en tres rangos de edad gestacional: 31 a 34, 28 a 30 y 23 a 27 semanas. Se utilizó Chi-cuadrado de Pearson para asociaciones entre variables categóricas, y T-Test o ANOVA para comparaciones entre variables continuas. RESULTADOS: Observamos diferencias significativas entre los valores promedio de T4L por rangos de edad gestacional (p = 0,000), estos fueron 1,13 ng/dl para el rango de 31 a 34 semanas, 1,03 ng/dl para el rango de 28 a 30 semanas y 0,92 ng/dl para el rango de 23 a 27 semanas; no observamos diferencias significativas en los niveles de TSH por categorías de edad gestacional (p = 0,663). CONCLUSIONES: Establecimos la distribución de los niveles de T4L y TSH en nuestra población de recién nacidos muy prematuros y prematuros extremos, encontrando diferencias con reportes anteriores.

INTRODUCTION: The thyroid function of the pretern infant is altered by the relative immaturity of the hypothalamus-pituitary thyroid gland axis, along with other factors such as the incidence of diseases or the use of some drugs. Currently, there is controversy over normal levels of free thyroxine (FT4) in preterm infants. Our objective was to determine the distribution of FT4 and TSH values in newborn younger than 32 weeks or 1500 g of birth weight at 15 days of chronological age, in the neonatology service at Dr. Hernán Henríquez Aravena Hospital, Temuco. PATIENTS AND METHOD: Cross-sectional study; the results of FT4 and TSH from a database of 308 newborns, were analyzed, which were categorized into three gestational age ranges, 31-34, 28-30 and 23-27 weeks. It was used Pearson Chi-square for comparisons between categorical variables, and T-Test or ANOVA for categorical-variable ratios. RESULTS: Significant differences were observed between the average values of FT4 by gestatio nal age ranges (p = 0.000), these were 1.13 ng/dl for the range of 31 to 34 weeks, 1.03 ng/dl for the range of 28 to 30 weeks and 0.92 ng/dl for the range of 23 to 27 weeks; we did not observe significant differences in TSH levels by gestational age categories (p = 0.663). CONCLUSIONS: We established the distribution of FT4 and TSH levels in our population of very preterm and extremely preterm infants, finding differences with previous papers.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome

ABSTRACT Objective The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. Materials and methods We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. Results The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Conclusion Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.

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.

Percutaneous laser ablation of benign thyroid nodules: a one year follow-up study / Ablação percutânea com laser de nódulos benignos de tireoide: um estudo de acompanhamento de um ano

ABSTRACT Objective To evaluate safety and effectiveness of nodule volume reduction and thyroid function after percutaneous laser ablation treatment in patients with benign nonfunctioning thyroid nodules. Methods Prospective single-center study, from January 2011 to October 2012, which evaluated 30 euthyroid and thyroid antibodies negative patients with benign solitary or dominant nodule with indication of treatment due to compressive symptoms and aesthetic disturbances. The clinical and laboratory (thyroid ultrasound, TSH, FT4, TG, TG-Ab, TPO-Ab and TRAb levels) evaluations were performed before the procedure, and periodically 1 week, 3 months and 6 months after. The ablation technique was performed under local anesthesia and sedation. In each treatment, one to three 21G spinal needle were inserted into the thyroid nodule. The laser fiber was positioned through the needle, which was then withdrawn 10mm to leave the tip in direct contact with the nodule tissue. Patients were treated with a ND: Yag-laser output power of 4W and 1,500 to 2,000J per fiber per treatment. The entire procedure was performed under US guidance. Results Thirty patients, with a total of 31 nodules submitted to laser ablation were evaluated. The median volumetric reduction of the nodule was approximately 60% after 12 months. No statistical significance was observed on thyroid function and antibodies levels. There was a peak on the level of thyroglobulin after the procedure due to tissue destruction (p<0.0001). No adverse effects were observed. Conclusion Percutaneous laser ablation is a promising outpatient minimally invasive treatment of benign thyroid nodule.

RESUMO Objetivo Avaliar a segurança e a efetividade da redução de volume nodular e função tireoidiana após tratamento com ablação percutânea por laser em pacientes com nódulos tireoidianos benignos não funcionantes. Métodos Estudo unicêntrico prospectivo, de janeiro de 2011 a outubro de 2012, que avaliou 30 pacientes eutireoideos (com anticorpos antitireoide negativos), com nódulo solitário ou dominante benigno, com indicação de tratamento devido a sintomas de compressão e distúrbios estéticos. As avaliações clínica e laboratorial (ultrassonografia de tireoide, TSH, FT4, TG, TG-Ab, TPO-Ab e TRAb) foram realizada antes do procedimento e periodicamente − 1 semana, 3 meses e 6 meses depois. A técnica de ablação consistiu em procedimento realizado sob a anestesia local e sedação. Em cada tratamento, uma a três agulhas espinhais 21G foram inseridas no nódulo tireoidiano. A fibra laser foi posicionada através da agulha que foi, então, retirada 10mm, para deixar a ponta em contato direto com o nódulo. Os pacientes foram tratados com uma potência de saída ND: Yag-laser de 4W e 1.500 a 2.000J por fibra por tratamento. Todo o procedimento foi guiado por ultrassonografia. Resultados Foram avaliados 30 pacientes, com total de 31 nódulos submetidos à ablação a laser. A redução média volumétrica do nódulo foi de aproximadamente 60% após 12 meses. Não foi observada significância estatística na função da tireoide e nem nos níveis de anticorpos. Houve pico no nível de tiroglobulina após o procedimento devido à destruição do tecido (p<0,0001). Nenhum efeito adverso foi observado. Conclusão A ablação com laser é um tratamento minimamente invasivo promissor para tratamento do nódulo benigno da tireoide.

Phonological acquisition in children with early-treated congenital hypothyroidism: association with clinical and laboratory parameters / Aquisição fonológica em crianças com hipotireoidismo congênito precocemente tratado: associação com dados clínicos e laboratoriais

ABSTRACT Purpose To evaluate the phonological characteristics of children with congenital hypothyroidism (CH). Methods Observational, analytical, cross-sectional, ambispective study including prepubertal children with CH (n=100; study group, SG) and controls without CH ( n=100; control group, CG). Assessments included a speech language pathology interview, the phonological evaluation of the ABFW Child Language Test, medical data, and neuropsychological tests in the first three years of life. Results On treatment onset of the SG, the median chronological age of the participants was 18.0 days and 48.4% had total T4 <2.5 µg/dL (31.75 nmol/L). At the age of 7 years, children in the SG had higher rates of consonant cluster simplification and lower rates of complete phonological system compared to those in the CG. On analysis of combined age groups (4+5 and 6+7 years), the CG had a higher frequency of complete acquisition versus the SG. On multivariate analysis, thyroid agenesis, abnormal scores on the Clinical Linguistic and Auditory Milestone Scale and developmental quotient tests were associated with the occurrence of phonological disorders. Conclusion Children with CH present delay in phonological acquisition, despite early diagnosis and adequate treatment, especially between the ages of 6-7 years. The etiology of CH and the results of neuropsychological tests in the first years of life seem to be related to this delay.

RESUMO Objetivo Avaliar as características fonológicas de crianças com hipotireoidismo congênito (HC). Método Estudo observacional, analítico, transversal e ambispectivo que incluiu crianças pré-púberes com HC (n = 100, Grupo de Estudo, GE) e um grupo controle de crianças pré-púberes sem HC (n = 100, Grupo Controle, GC). As avaliações incluíram uma entrevista fonoaudiológica, avaliação fonológica por meio do teste de linguagem infantil ABFW, e coleta de dados nos prontuários referentes às avaliações médicas e testes neuropsicológicos realizados nos três primeiros anos de vida. Resultados Quanto ao início do tratamento no GE, a idade cronológica mediana dos participantes foi de 18,0 dias e 48,4% apresentaram T4 total <2,5 μg / dL (31,75 nmol / L). Na comparação da avaliação fonológica por idade, aos 7 anos as crianças no GE tiveram maior ocorrência de simplificação de encontros consonantais e menor ocorrência de sistema fonológico completo quando comparadas às crianças do GC. Na análise de grupos etários combinados (4 + 5 e 6 + 7 anos), observou-se que o GC teve aquisição completa do sistema fonológico mais precocemente. Na análise multivariada, agenesia da tireoide, resultados alterados nos testes Clinical Linguistic and Auditory Milestone Scale (CLAMS) e Developmental Quotient Tests (CDC) foram associados à ocorrência de desvios fonológicos. Conclusão Crianças com HC apresentam atraso na aquisição fonológica, mesmo com diagnóstico precoce e tratamento adequado, especialmente entre as idades de 6-7 anos. A etiologia do HC, bem como os resultados obtidos nos testes neuropsicológicos nos primeiros anos de vida, parecem ter relação com este atraso.