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BACKGROUND: Thyroid dysfunction has been associated with cognitive decline and dementia. However, the role of subtle thyroid hormone alterations in cognitive function is still debatable. METHODS: Participants without overt thyroid dysfunction aged 35-74 years at baseline were evaluated in 3 study waves (2008-2010, 2012-2014, and 2017-2019). We assessed baseline thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognitive performance was evaluated every 4 years in each wave using 10-word immediate and late recall, word recognition, semantic (animals category) and phonemic (letter f) verbal fluency, and the trail-making B-version tests. A global composite z-score was derived from these tests. The associations of TSH, FT4, and FT3 levels with cognitive decline over time were evaluated using linear mixed-effect models adjusted for sociodemographic, clinical, and lifestyle variables. RESULTS: In 9 524 participants (mean age 51.2 ±â€…8.9 years old, 51% women, 52% White), there was no association between baseline TSH, FT4, and FT3 levels and cognitive decline during the follow-up. However, increase in FT4 levels over time was associated with faster memory (ß = -0.004, 95% CI = -0.007; -0.001, p = .014), verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0005, p = .021), executive function (ß = -0.004, 95% CI = -0.011; -0.003, p < .001), and global cognition decline (ß = -0.003, 95% CI = -0.006; -0.001, p = .001). Decrease in FT4 levels over time was associated with faster verbal fluency (ß = -0.003, 95% CI = -0.007; -0.0004, p = .025) and executive function (ß = -0.004, 95% CI = -0.007; -0.0003, p = .031) decline. CONCLUSIONS: An increase or decrease in FT4 levels over time was associated with faster cognitive decline in middle-aged and older adults without overt thyroid dysfunction during 8 years of follow-up.

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The association between hypertension and obesity-induced cardiac damage is usually accepted. However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It is well known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development of hypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-ß) and hypertrophic markers (BNP and ß-MHC) expression vs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20 mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression, pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophic markers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally prevent LVH development and cardiac fibrosis.

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PURPOSE OF REVIEW: This review aims to explore in-depth the different aspects of the association between very low-calorie ketogenic diet (VLCKD), obesity and obesity-related thyroid dysfunction. RECENT FINDINGS: The VLCKD, proposed as a non-pharmacological strategy for the management of certain chronic diseases, is becoming increasingly popular worldwide. Initially used to treat epilepsy, it has been shown to be effective in controlling body weight gain and addressing various pathophysiological conditions. Research has shown that a low-calorie, high-fat diet can affect thyroid hormone levels. Weight loss can also influence thyroid hormone levels. Studies have suggested that long-term use of VLCKD for refractory epilepsy may be related to the development of hypothyroidism, with an effect seen in various populations. In particular, women with obesity following VLCKD tend to have reduced T3 levels. We propose further research to unravel the underlying mechanisms linking VLCKD to obesity and obesity-related thyroid dysfunction.

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ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians' preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

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Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto's thyroiditis (HT) and hyperthyroidism (Graves-Basedow disease (GBD)). Both conditions are characterized by presenting a cellular and humoral autoimmune reaction, with an increase in the synthesis and secretion of antibodies directed toward various thyroid antigens, together with a phenomenon of thyrocyte necrosis and apoptosis (in HT) and a persistent thyrotropin-receptor stimulation (in GBD). The diagnosis of both entities is based on clinical, laboratory, and imaging findings. Three major anti-thyroid antibodies have been described, those directed against the TSH receptor (TRAb), against thyroid peroxidase (TPOAb), and against thyroglobulin (TgAb). Each of these autoantibodies plays a fundamental role in the diagnostic approach of autoimmune thyroid disease. TRAbs are the hallmark of GBD, and additionally, they are predictors of response to disease treatment, among other utilities. Likewise, TPOAb and TgAb allow for identifying individuals with a higher risk of progression to hypothyroidism; the positivity of one or both autoantibodies defines the presence of thyroid autoimmunity. In this review, the usefulness of anti-thyroid antibodies in the diagnostic approach to autoimmune thyroid disease is described.

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Thyrotropin-releasing hormone (TRH) is a tripeptide that regulates the neuroendocrine thyroid axis. Moreover, its widespread brain distribution has indicated that it is a relevant neuromodulator of behaviors such as feeding, arousal, anxiety, and locomotion. Importantly, it is also a neurotrophic peptide, and thus may halt the development of neurodegenerative diseases and improve mood-related disorders. Its neuroprotective actions on those pathologies and behaviors have been limited due to its poor intestinal and blood-brain barrier permeability, and because it is rapidly degraded by a serum enzyme. As new strategies such as TRH intranasal delivery emerge, a renewed interest in the peptide has arisen. TRH analogs have proven to be safe in animals and humans, while not inducing alterations in thyroid hormones' levels. In this review, we integrate research from different approaches, aiming to demonstrate the therapeutic effects of TRH, and to summarize new efforts to prolong and facilitate the peptide's actions to improve symptoms and the progression of several pathologies.

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Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

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BACKGROUND: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the association of TSH and free T4 (FT4) with the severity and persistence of fatigue. METHODS: A prospective study was performed in 92 patients with primary hypothyroidism. Fatigue severity scale (FSS) scores and clinical and biochemical characteristics before and at 6 months of levothyroxine were evaluated. RESULTS: After 6 months of levothyroxine, a reduction in FSS (53 (47-57) vs. 36 (16-38); p = 0.001) and fatigue frequency (45.7% vs. 26.1%; p = 0.008) was evident. Both before and after 6 months of levothyroxine, there was a positive correlation of the FSS score with TSH and a negative correlation with FT4. Persistent fatigue was associated with a pretreatment FSS score (r = 0.75; p = 0.001) and diabetes (r = 0.40; p = 0.001). An FSS > 34 (RR 3.9 (95% CI 1.43-10.73; p = 0.008)), an FSS > 36 (RR 3.23 (95% CI 1.21-8.6; p = 0.019)), and diabetes (RR 5.7 (95% CI 1.25-9.6; p = 0.024)) before treatment were risk factors for persistent fatigue. CONCLUSIONS: Levothyroxine improved fatigue in most patients. Diabetes and an FSS score >34 or >36 before treatment were risk factors for persistent fatigue.

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Hypothyroidism exerts deleterious effects on immunity, but the precise role of the hypothalamic-pituitary-thyroid (HPT) axis in immunoregulatory and tolerogenic programs is barely understood. Here, we investigated the mechanisms underlying hypothyroid-related immunosuppression by examining the regulatory role of components of the HPT axis. We first analyzed lymphocyte activity in mice overexpressing the TRH gene (Tg-Trh). T cells from Tg-Trh showed increased proliferation than wild-type (WT) euthyroid mice in response to polyclonal activation. The release of Th1 pro-inflammatory cytokines was also increased in Tg-Trh and TSH levels correlated with T-cell proliferation. To gain further mechanistic insights into hypothyroidism-related immunosuppression, we evaluated T-cell subpopulations in lymphoid tissues of hypothyroid and control mice. No differences were observed in CD3/CD19 or CD4/CD8 ratios between these strains. However, the frequency of regulatory T cells (Tregs) was significantly increased in hypothyroid mice, and not in Tg-Trh mice. Accordingly, in vitro Tregs differentiation was more pronounced in naïve T cells isolated from hypothyroid mice. Since Tregs overexpress galectin-1 (Gal-1) and mice lacking this lectin (Lgals1-/- ) show reduced Treg function, we investigated the involvement of this immunoregulatory lectin in the control of Tregs in settings of hypothyroidism. Increased T lymphocyte reactivity and reduced frequency of Tregs were found in hypothyroid Lgals1-/- mice when compared to hypothyroid WT animals. This effect was rescued by the addition of recombinant Gal-1. Finally, increased expression of Gal-1 was found in Tregs purified from hypothyroid WT mice compared with their euthyroid counterpart. Thus, a substantial increase in the frequency and activity of Gal-1-expressing Tregs underlies immunosuppression associated with hypothyroid conditions, with critical implications in immunopathology, metabolic disorders, and cancer.

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Arapaima gigas, known as Pirarucu in Brazil, is one of the largest freshwater fish in the world. Some individuals could reach 3 m in length and weight up to 200 kg. Due to extinction risks and its economic value, the species has been a focus for preservation and reproduction studies. Thyrotropin (TSH) is a glycoprotein hormone formed by 2 subunits α and ß whose main activity is related to the synthesis of thyroid hormones (THs)-T3 and T4. In this work, we present a combination of bioinformatics tools to identify Arapaima gigas ßTSH (ag-ßTSH), modeling its molecular structure and express the recombinant heterodimer form in mammalian cells. Using the combination of computational biology, based on genome-related information, in silico molecular cloning and modeling led to confirm results of the ag-ßTSH sequence by reverse transcriptase-polymerase chain reaction (RT-PCR) and transient expression in human embryonic kidney (HEK293F) cells. Molecular cloning of ag-ßTSH retrieved 146 amino acids with a signal peptide of 21 amino acid residues and 6 disulfide bonds. The sequence has a similarity to 39 fish species, ranging between 43.1% and 81.6%, whose domains are extremely conserved, such as cystine knot motif and N-glycosylation site. The Arapaima gigas thyrotropin (ag-TSH) model, solved by AlphaFold, was used in molecular dynamics simulations with Scleropages formosus receptor, providing similar values of free energy ΔGbind and ΔGPMF in comparison with Homo sapiens model. The recombinant expression in HEK293F cells reached a yield of 25 mg/L, characterized via chromatographic and physical-chemical techniques. This work shows that other Arapaima gigas proteins could be studied in a similar way, using the combination of these techniques, recovering more information from its genome and improving the reproduction and preservation of this prehistoric fish.

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Objective: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusion: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased.

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OBJECTIVES: This study aims to investigate the population status of selenium in Colombia and other associated factors. METHODS: Cross-sectional study, in population of urban or rural origin (n=412). Main outcome measures were: median serum selenium, thyrotropin, the prevalence of and positivity of anti-thyroid peroxidase, anti-thyroglobulin, and anti-TSH receptor. RESULTS: This study found that 96.6% of the subjects had normal selenium levels, and no significant associations were found between the population median of selenium and overweight/obesity, sociodemographic variables, age, goiter, and thyroid antibody positivity. CONCLUSIONS: In Colombia, the population status of selenium is normal, and the geological characteristics may contribute to the state of selenium in this population. However, additional studies are required to evaluate the content of selenium in plants and other foods.

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Introducción: Los parámetros de función tiroidea en las embarazadas se modifican durante el embarazo y son específicos para cada población. Objetivo: Establecer los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas. Métodos: Estudio transversal, en el municipio Plaza de la Revolución de La Habana, Cuba, a 362 gestantes sin antecedentes personales o familiares de enfermedad tiroidea, con anticuerpos anti-tiroideos negativos y ausencia de lesiones en el ultrasonido tiroideo. Se analizaron edad materna, edad gestacional, raza, hábito de fumar, paridad, uso de suplementos yodados, índice de masa corporal, tirotropina, tiroxina total y libre, triyodotironina total y libre. Se establecieron los intervalos de referencia para cada parámetro mediante los percentiles 2,5 y 97,5 como límites inferior y superior, respectivamente. Resultados: Los valores de referencia en el primer, segundo y tercer trimestres fueron para la tirotropina 0,1-3,3 mUI/L, 0,6-3,4 mUI/L y 0,3-3,9 mUI/L; para la TT4 90,1-204,1 nmol/L, 92,2-189,2 nmol/L y 79,8-170,4 nmol/L; para la FT4 7,3-16,7 pmol/L, 6,3-17,3 pmol y 5,6-12,7 pmol/L; para la TT3 1,8-3,9 nmol/L, 1,8-3,9 nmol/L y 1,7-4,0 nmol/L y para la FT3 1,0-7,4 pmol/L, 0,7-6,3 pmol/L y 0,7-5,4 pmol/L, respectivamente. Conclusiones: Se determinaron por primera vez los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas; estos difieren de los establecidos por los kits diagnósticos y de los recomendados por las guías internacionales previas (AU)

Introduction: Thyroid function parameters in pregnant women are modified during pregnancy and are specific for each population. Objective: To establish reference values for thyrotropin and thyroid hormones in a population of Cuban pregnant women. Methods: Cross-sectional study, in the Plaza de la Revolución municipality, of 362 pregnant women without personal or family history of thyroid disease, with negative anti-thyroid antibodies and absence of lesions in the thyroid ultrasound. Maternal age, gestational age, race, smoking, number of pregnancies, use of iodine supplements, body mass index, thyrotropin, total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine were analyzed. Reference intervals were established for each parameter using the 2.5 and 97.5 percentiles as lower and upper limits, respectively. Results: The reference values in the first, second and third trimesters were for thyrotropin 0.1-3.3 mIUI/L, 0.6-3.4 mIU/L and 0.3-3.9 mIU/L; for TT4 90.1-204.1 nmol/L, 92.2-189.2 nmol/L and 79.8-170.4 nmol/L; for FT4 7.3-16.7 pmol/L, 6.3-17.3 pmol and 5.6-12.7 pmol/L; for TT3 1.8-3.9 nmol/L, 1.8-3.9 nmol/L and 1.7-4.0 nmol/L and for FT3 1.0-7.4 pmol/L, 0.7-6.3 pmol/L and 0.7-5.4 pmol/L, respectively. Conclusions: Reference values for thyrotropin and thyroid hormones were determined for the first time in a population of Cuban pregnant women. These values differ from those established by the manufacturer of the diagnostic kits and from those recommended by previous international guidelines (AU)

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ABSTRACT Objectives: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusions: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased.

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BACKGROUND: Thyroid function is one of the most current procedures in the evaluation of endocrine function performed in daily practice; the reference intervals for thyrotropin (TSH) depend on the assay technology and the instruments in each laboratory. The main objective of this study is to determine the thyrotropin reference values in patients considered as euthyroid, living in the Andean region, at 2850 meters above sea level (Quito, Ecuador). METHODS: A cross-sectional, analytical, epidemiological study was conducted using a sample of 595 healthy adult volunteer donors from the Military Hospital Blood Bank in Quito-Ecuador. Serum samples were analyzed for thyrotropin levels using electrochemiluminescence. The reference values were calculated using recommendations from the CLSI C28A3 guide. RESULTS: The mean age of the overall sample was 35.7 (7.2) years, 50.9% (n = 303) were women. TSH recovered in the total sample showed a median of 2.64 mIU/L (2.5th-97.5th percentiles: 0.91-8.35 mIU/L); after removing outliers the reference values for the studied population were 0.87 to 5.21 mIU/L, without differences by sex. CONCLUSIONS: General laboratory practice should improve harmonization of TSH assays. This is a must in daily clinical practice, since it would allow us to share real reference intervals in an established population and may be related to the presence or absence of thyroid pathology.

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Background: This study aimed to investigate the iodine status and its potential effects on thyroid function and autoimmunity in Colombia. Methods: This was a cross-sectional study, in population of urban and rural areas, from four geographic regions in the Department of Cauca, Colombia; the participants were 412 healthy adults, a third from rural areas. The following variables were evaluated: median urinary iodine concentration (mUIC), serum thyrotropin (TSH), clinical and ultrasonographic (US) goiter assessment, and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg) and anti-TSH receptor (TRAb) concentrations. Results: The mUIC levels were 153.9 µg/L (interquartile range (IQR): 220.06); 30% had "excessive" mUIC and a quarter had "low" mUIC. The positivity of anti-Tg and anti-TPO was higher in subjects > 60 years (P = 0.017 and P ≤ 0.001, respectively). A high prevalence of "low" mUIC was found in the "low" socioeconomic status (SES) and of "more than adequate or excessive" in the "high" SES when compared with the "medium" SES (P ≤ 0.001). The prevalence of goiter by physical examination was 41.7% and 34% by US. The highest mUIC levels were significantly more prevalent in women, in subjects with elevated TSH and in those from rural areas. Conclusions: The population status of iodine in Colombia is U-shaped; the high prevalence of goiter, hypothyroidism, and thyroid autoimmunity can be explained by excess or deficit of iodine and by probable environmental goitrogens.

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ABSTRACT Objective: To assess thyroid function in very preterm or very low birth weight (VLBW) neonates by measuring combination levels of thyroid-stimulating hormone TSH and free T4 (FT4) Methods: Inclusion criteria were defined as all very preterm (gestational age <32 weeks) or VLBW (birth weight ≤1500g) neonates with initial Thyroid Function Test (TFT) who were admitted to the Neonatal Intense Care Unit (NICU) of Taleghani Hospital, Tabriz, Iran, from March 2015 to March 2016. Exclusion criteria were the absence of initial TFT with any major congenital anomaly. The primary value of TSH was evaluated at 3-5 days, and mean levels of TSH with FT4 were measured at 2, 4, and 8-weeks. Results: Ninety-five neonates with a mean gestational age of 29.5 weeks were included, and the mean levels of thyrotropin and FT4 at postnatal week two were 4.4mIU/L and 1.4ng/dL, respectively. Two of the patients had serum TSH concentration >25mIU/L that was considered as permanent primary hypothyroidism. Among nine hypothyroxinemia cases, two had elevated TSH levels (10.8±0.4mIU/L at the end of 8 weeks) and normal FT4 concentration, and were considered transient hypothyroidism. Seven cases had normal TSH levels (1.6±1.0mIU/L at 2 weeks, 3.5±2.8mIU/L at 8 weeks) and low FT4 concentrations. Conclusions: Combined venous TSH and FT4 concentration at the end of the first postnatal month can be an efficient approach for detecting neonatal hypothyroidism.

RESUMO Objetivo: Avaliar a função da tireoide em recém-nascidos muito prematuros ou de muito baixo peso por meio dos níveis de combinação de TSH e T4 livre (FT4). Métodos: Os critérios de inclusão foram: todos os recém-nascidos muito prematuros (idade gestacional <32 semanas) ou de muito baixo peso (peso ao nascer ≤500g) com teste de função tireoidiana inicial e que foram admitidos na Unidade de Terapia Intensiva Neonatal do Hospital de Taleghani, Tabriz, Irã, de março de 2015 a março de 2016. Os critérios de exclusão foram: ausência de TFT inicial com qualquer anomalia congênita importante. Resultados: 95 neonatos com idade gestacional média de 29.5 semanas foram incluídos, e os níveis médios de tireotropina e FT4 na 2ª semana pós-natal foram 4.4mIU/L e 1.4ng/dL, respectivamente. Dois dos pacientes apresentavam concentração sérica de TSH >25mIU/L, considerada hipotireoidismo primário permanente. Entre nove casos de hipotiroxinemia, dois tinham níveis elevados de TSH (10.8±0.4mIU/L ao final de 8 semanas) e concentração normal de FT4 e foram considerados hipotireoidismo transitório. Sete casos tinham níveis normais de TSH (1,6±1,0mIU/L em 2 semanas, 3,5±2,8mIU/L em 8 semanas) e baixas concentrações de FT4. Conclusões: A concentração combinada de TSH e FT4 venoso no final do primeiro mês pós-natal pode ser uma abordagem eficiente para detectar hipotireoidismo neonatal.

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The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words: "sex dimorphic" or "sex differences" or "female" or "women" and "thyrotropin" or "thyroid hormones" or "deiodinases" and "energy homeostasis" or "stress". The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.

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BACKGROUND: Subtle thyroid alterations have a controversial role in cognition. OBJECTIVE: We investigated the longitudinal association of baseline thyroid function, thyrotropin (TSH), and thyroxine (FT4) levels with cognitive performance after 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction. METHODS: We included 4,473 individuals, age≥55 years at the second study wave, without overt thyroid dysfunction at baseline. Individuals were divided according to thyroid function and TSH and FT4 tertiles. Cognition was assessed at baseline and after 4 years of follow-up by the word recall (DWR), semantic verbal fluency (SVF), and trail making (TMT) tests. The longitudinal association of thyroid function and TSH and FT4 tertiles with cognitive performance was investigated using generalized estimating equations adjusted for sociodemographic characteristics, lifestyle, cardiovascular risk factors and depression. RESULTS: There was no longitudinal association of thyroid function and TSH and FT4 baseline levels with performance on the cognitive tests. However, there was a baseline cross-sectional U-shaped association of FT4 tertiles with poorer performance in the SVF (first FT4 tertile: ß= -0.11, 95% CI = -0.17; -0.04; third FT4 tertile: ß= -0.10, 95% CI = -0.17; -0.04) and of the third FT4 tertile with poorer performance in the DWR (ß= -0.09, 95% CI = -0.16; -0.02). CONCLUSION: Thyroid function and hormone levels were not associated with cognitive decline during 4 years of follow-up in middle-aged and older adults without overt thyroid dysfunction. Future studies with longer follow-up could clarify the implications of subtle thyroid alterations in cognition.

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RESUMO

ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

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