Adverse perinatal conditions and the developmental origins of thyroid dysfunction-Lessons from Animal Models.

PURPOSE: Nutritional, hormonal, and environmental status during development can predispose the individual to obesity and endocrine diseases later in life, an association known as metabolic programming. In general, weight loss or gain are seen in thyroid disorders, and thyroid function can be affected by body adiposity. In addition, hyper- and hypothyroidism can be related to metabolic programming. Our aim was to gather evidence that regardless of the type or critical window of metabolic imprinting, offspring exposed to certain adverse perinatal conditions have a higher risk of developing thyroid dysfunction. METHODS: We reviewed literature data that relate insults occurring during pregnancy and/or lactation to short- and long-term offspring thyroid dysfunction in animal models. RESULTS: Few studies have addressed the hypothalamic-pituitary-thyroid axis and thyroid dysfunction related to metabolic programming. The literature shows that under- and overnutrition, exposure to endocrine disruptors, early weaning, maternal thyroid disease and maternal high-fat diet can induce alterations in offspring thyroid function in a sex-dependent manner. CONCLUSION: Based on the few available data, mainly in rodent models, we can conclude that diet, hormones, and environmental contaminants are related to the developmental origins of later thyroid dysfunction by interrupting the normal maturation of the thyroid gland.

The impact of pre-existing thyroid diseases on susceptibility to respiratory infections or self-reported sickness during the SARS-CoV-2 pandemic

ABSTRACT Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. Subjects and methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

Association of methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis

ABSTRACT Recent studies have shown that two common methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis.

Recent studies have shown that two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

The impact of pre-existing thyroid diseases on susceptibility to respiratory infections or self-reported sickness during the SARS-CoV-2 pandemic.

Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands. Subjects and methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC. Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures. Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

Maternal Hyperthyroidism in Rats Alters the Composition and Gene Expression of the Matrix Produced In Vitro by Chondrocytes from Offspring with Intrauterine Growth Restriction.

Herein, we aimed to evaluate cultures of femoral chondrocytes from offspring of rats with intrauterine growth restriction (IUGR) induced by maternal hyperthyroidism. Fourteen adult female Wistar rats were divided into two groups, a control group and a group treated with daily L-thyroxine administration using an orogastric tube (50 µg/animal/day) during pregnancy. Three days after birth, the offspring were euthanized for chondrocyte extraction. At 7, 14, and 21 days, viability and alkaline-phosphatase (ALP) activity were assessed using the MTT assay and BCIP/NBT method, respectively, in a 2D culture. Pellets (3D cultures) were stained with periodic acid Schiff (PAS) to assess the morphology and percentage of PAS+ areas. The gene transcripts for Col2, Col10, Acan, Sox9, and Runx2 were evaluated by qRT-PCR. The MTT and ALP-assay results showed no significant differences between the groups. Maternal hyperthyroidism did not alter the chondrocyte morphology, but significantly reduced the percentage of PAS+ areas, decreased the expression of the gene transcripts of Col2 and Acan, and increased Sox9 expression. Maternal hyperthyroidism in rats alters the composition and gene expression of the matrix produced by chondrocytes from offspring with IUGR. This may be one of the mechanisms through which excess maternal thyroid hormones reduce offspring bone growth.

Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru.

Background: Reversible etiologies of cognitive impairment are common and treatable, yet the majority of mild cognitive impairment (MCI) and dementia research in Latin America has focused on irreversible, neurodegenerative etiologies. Objective: We sought to determine if thyroid dysfunction and vitamin B12 and folate deficiencies are associated with cognitive disorders among older adults with memory complaints in Lima, Peru. Methods: This was a retrospective review of patients who presented for cognitive evaluations to a multidisciplinary neurology clinic in Lima, Peru from January 2014 to February 2020. We included individuals aged ≥60 years, native Spanish-speakers, with at least a primary school educational level and a complete clinical assessment. Patients had either subjective cognitive decline (SCD), MCI, or dementia. One-way ANOVA and multiple logistic regression analyses were performed. Results: We included 720 patients (330 SCD, 154 MCI, and 236 dementia); the dementia group was significantly older [mean age SCD 69.7 ± 4.1, dementia 72.4 ± 3.7 (p = 0.000)] and had lower folate levels than SCD patients. The MCI group had higher free T3 levels compared with SCD patients. Those with lower TSH had greater dementia risk (OR = 2.91, 95%CI: 1.15-6.86) but not MCI risk in unadjusted models. B12 deficiency or borderline B12 deficiency was present in 34% of the dementia group, yet no clear correlation was seen between neuropsychological test results and B12 levels in our study. There was no association between MCI or dementia and thyroid hormone, B12 nor folate levels in adjusted models. Conclusion: Our findings do not support an association between metabolic and endocrine disorders and cognitive impairment in older Peruvians from Lima despite a high prevalence of B12 deficiency. Future work may determine if cognitive decline is associated with metabolic or endocrine changes in Latin America.

Disfunción tiroidea y diabetes mellitus tipo 1 / Thyroid dysfunction and type 1 diabetes mellitus

Introducción: La diabetes mellitus tipo 1 es una enfermedad autoinmunitaria que se relaciona con alteraciones tiroideas. Objetivo: Describir la relación que existe entre diabetes mellitus tipo 1 y enfermedad tiroidea autoinmune. Métodos: Se realizó una revisión de la literatura nacional e internacional de los últimos 15 años en bases de datos, en español y en inglés. Se utilizaron las siguientes palabras clave: diabetes mellitus tipo 1, autoinmunidad, enfermad tiroidea autoinmune, disfunción tiroidea y anticuerpos antitiroideos. Análisis e integración de la información: La alteración más frecuente es el hipotiroidismo subclínico y se presenta con mayor frecuencia en el sexo femenino, por lo que se sugiere realizar periódicamente el perfil tiroideo a estos pacientes. Conclusiones: Se debe tener en cuenta en la práctica clínica estas implicaciones para brindar un tratamiento oportuno, mejorar complicaciones derivadas como las enfermedades cardiovasculares y disminuir las cifras de morbilidad y mortalidad(AU)

Introduction: Type 1 diabetes mellitus is an autoimmune disease that is related to thyroid abnormalities. Objective: Describe the relationship between type 1 diabetes mellitus and autoimmune thyroid disease. Methods: A review of the national and international literature of the last 15 years was carried out in databases, in Spanish and in English. The following keywords were used: type 1 diabetes mellitus, autoimmune, autoimmune thyroid disease, thyroid dysfunction and antithyroid antibodies. Analysis and integration of information: The most common alteration is subclinical hypothyroidism and it occurs most often in the female sex, so it is suggested to periodically perform the thyroid profile to these patients. Conclusions: These implications should be taken into account in clinical practice to provide timely treatment, improve complications such as cardiovascular disease and reduce morbidity and mortality figures(AU)

Thyroid-stimulating hormone levels and incident depression: Results from the ELSA-Brasil study.

OBJECTIVE: This study aimed to prospectively evaluate whether TSH levels at baseline were associated with incident depression after four years of follow-up in a cohort of middle-aged adults, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: TSH and free-thyroxine (FT4) levels were evaluated at baseline. Depression diagnoses were performed using the Clinical Interview Schedule-Revised (CIS-R) at baseline and after a 4-year follow-up. Poisson regression models (95% Confidence Intervals) were built to evaluate the association between TSH quintiles at baseline and incident depression. All analyses were stratified by sex. Models were presented crude, adjusted for age and sex; and further adjusted for race, education, BMI, smoking, alcohol consumption, use of antidepressants/benzodiazepines, kidney function and comorbidities. RESULTS: Mean age was 51.5 years, and 51.2% were women. Overall, low TSH levels (1st quintile) were associated with incident depression (adjusted RR = 1.36, 95% CI 1.02-1.81), remaining significant for women (adjusted RR = 1.64, 95% CI 1.15-2.33), but not for men. The same results were found when restricting analysis to euthyroid participants (adjusted RR = 1.46, 95% CI 1.08-1.99), also significant for women only (adjusted RR = 1.63, 95% CI 1.12-2.38). CONCLUSIONS: Our results showed that low TSH levels were positively associated with incident depression, particularly among women. Similar results were found when restricting the analysis to euthyroid participants. In contrast, high TSH levels were inversely associated with incident depression, also among women.

Prevalence of thyroid dysfunction in healthy adults according to the estimated iodine intake in 24-hour urine samples: The SALMEX cohort.

PURPOSE: The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). METHODS: From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants' sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. RESULTS: The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 µg/d (IQR 215.0-369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p= 0.606). CONCLUSIONS: Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.

Unfavorable Triglyceride-rich Particle Profile in Subclinical Thyroid Disease: A Cross-sectional Analysis of ELSA-Brasil.

Subclinical thyroid disorders have been associated with atherosclerosis and increased cardiovascular risk. As triglyceride-rich lipoprotein particles (TRLPs) have recently emerged as a casual factor for atherogenesis, the aim of this study was to evaluate the relationship between subclinical hypo- and hyperthyroidism and TRLP subfractions. We selected 5066 participants from the ELSA-Brasil cohort with available data of thyroid function and lipid profile measured by nuclear magnetic resonance (NMR) spectroscopy. Individuals were divided into 3 groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). Triglyceride-rich lipoprotein particle subfractions were analyzed through NMR spectroscopy. To examine the association between TRLP subfractions and thyroid function, we conducted univariate and multivariate linear regression models adjusted for demographic characteristics, body mass index, diabetes, smoking status, and alcohol use. Of 3304 individuals, 54% were women, with a mean age of 50.6 ± 8.7 years, 51% white, and 53% with at least a college education. Of these individuals, 92% were euthyroid, whereas 6.8% had subclinical hypothyroidism and 1.2% had subclinical hyperthyroidism. The univariate linear regression showed that very small TRLPs (P = 0.026) and very large TRLPs (P = 0.008) were statistically increased in subclinical hypothyroidism when compared with euthyroidism. In subclinical hyperthyroidism, there was a reduction in total TRLPs (P = 0.003), seemingly driven by reduced very small TRLPs (P = 0.067). The findings were confirmed when adjusted for demographic characteristics, as well as comorbidities. This study suggests that subclinical hypothyroidism is associated with very small and very large TRLPs, which are related to an unfavorable atherogenic profile. Subclinical hyperthyroidism is associated to lower very small TRLPs.

Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis.

Background: Levothyroxine (LT4) is one of the most commonly prescribed medications. Although considered a life-long replacement therapy, LT4 therapy can be discontinued for some patients. This study aims at: (i) reviewing the evidence on clinical outcomes of patients undergoing thyroid hormone replacement discontinuation, (ii) identifying the predictors of successful discontinuation, and (iii) systematically appraising frameworks used for deprescribing thyroid hormone. Methods: We searched multiple bibliographic databases, including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus, from inception to February 2020 for studies in which thyroid hormone replacement was discontinued. Clinical outcomes assessed included: proportion of patients that remained euthyroid or needed to restart thyroid hormone replacement after discontinuation and frequency of clinical symptoms of hypothyroidism and adverse effects. We also evaluated predictors for discontinuation and deprescribing frameworks. Reviewers (F.J.K.T., N.B., N.M.S.O., S.M.) evaluated studies for inclusion, extracted data, and assessed methodological quality independently and in duplicate. Results: Seventeen observational studies at moderate to high risk of bias met inclusion criteria, including a total of 1103 patients (86% women) with an age range of 2-81 years. Approximately a third of patients undergoing thyroid hormone discontinuation remained euthyroid at follow-up (37.2%, 95% confidence interval [CI 24.2-50.1%], I2 97.5%). Subgroup analysis showed that patients with a previous diagnosis of overt hypothyroidism (OH) were less likely to remain euthyroid (11.8% [CI 0.4-23.2%], I2 90.3%) than patients with a prior diagnosis of subclinical hypothyroidism (SCH) (35.6% [CI 8.2-62.9%], I2 94.0%). No study followed a framework for systematically deprescribing LT4. Conclusions: Low-quality evidence suggests that up to a third of patients remained euthyroid after thyroid hormone discontinuation, with a higher proportion of patients with an initial diagnosis of SCH remaining euthyroid than patients with an initial diagnosis of OH. A deprescribing framework focusing on adequate selection of patients for deprescribing LT4 and a systematic process is warranted to guide clinicians in re-evaluating the need for LT4 in their patients.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Thyroid function before and after Roux-en-Y gastric bypass: an observational study.

BACKGROUND: Population studies have shown a positive association between thyroid-stimulating hormone (TSH) and body mass index. Recent studies have shown a significant increase in the prevalence of subclinical hypothyroidism (SCH) in obesity. Weight reduction after Roux-en-Y gastric bypass (RYGB) seems to significantly decrease TSH levels. OBJECTIVES: The purpose of this study was to evaluate the prevalence of SCH in obese patients (class II and III) and to observe the behavior of thyroid hormones (TSH, hormone triiodothyronine, thyroxine, free thyroxine) with significant weight loss after RYGB. SETTING: Hospital Nossa Senhora das Graças, Curitiba, Paraná, Brazil. METHODS: We retrospectively reviewed the medical records of 215 obese patients who underwent RYGB between 2005 and 2012 with a follow-up of at least 2 years. The study was observational and descriptive. The selected times for clinical and laboratory evaluations were preoperative, 3, 6, 12, and 24 months after the procedure. Association, correlation, and variance analyses were performed. RESULTS: The prevalence of SCH preoperatively was 9.3%. SCH was corrected in 89.5% of patients 12 months after RYGB. We did not find an association between TSH and BMI (r = .002, P = .971). There was a positive impact of bariatric surgery on all metabolic variables. We showed that serum TSH level had no positive correlation with the presence or absence of metabolic syndrome. CONCLUSIONS: Weight loss after bariatric surgery leads to normalization of TSH levels in most patients and none developed overt hypothyroidism. Obese patients with SCH should not be treated with thyroid hormone replacement. Serial monitoring of thyroid function after obesity therapy seems to be a reasonable approach.

Asociación de disfunción tiroidea subclínica con el síndrome de fragilidad en pacientes adultos mayores / Relation of subclinical thyroid dysfunction to frailty syndrome in older patients

Resumen OBJETIVO: Evaluar la asociación entre disfunción tiroidea subclínica y síndrome de fragilidad en pacientes adultos mayores. MATERIAL Y MÉTODO: Estudio de casos y controles efectuado de enero de 2016 a junio de 2017 en adultos mayores con síndrome de fragilidad (casos) y sin síndrome de fragilidad (controles). El diagnóstico de síndrome de fragilidad se estableció con los criterios de Fried. Se compararon las concentraciones séricas de TSH y T4 libre en pacientes robustos, prefrágiles y frágiles. También se determinó la razón de momios (OR) para fragilidad en pacientes con hipotiroidismo subclínico e hipertiroidismo subclínico. RESULTADOS: La edad promedio de los casos (n = 100) y controles (n = 104) fue de 83.2 y 78.1 años, respectivamente (p ≤ 0.01). Las concentraciones de TSH en sujetos frágiles en comparación con pacientes robustos fueron 3.1 vs 2.7 ng/mL (p = 0.5) y las concentraciones séricas de T4 libre fueron 1.26 y 1.32 ng/dL, respectivamente (p = 0.315). El OR para fragilidad en pacientes con hipotiroidismo subclínico fue de 1.21 (IC95% 0.39-3.80, p = 0.740) y en pacientes con hipertiroidismo subclínico fue OR = 0.74 (IC95% 0.14-3.75, p = 0.714). CONCLUSIONES: No existen diferencias significativas en las concentraciones séricas de TSH ni T4 libre entre pacientes frágiles y robustos. El hipotiroidismo y el hipertiroidismo subclínico no se asociaron con mayor riesgo de síndrome de fragilidad.

Abstract OBJECTIVE: To evaluate the association between subclinical thyroid dysfunction and frailty syndrome in elderly patients. MATERIAL AND METHOD: A case-control study was carried out from January 2016 to June 2017 in older adults with frailty syndrome (cases) and without frailty syndrome (controls). The diagnosis of frailty syndrome was made according to the Fried criteria. The serum levels of TSH and free-T4 were compared in robust, pre-frailty and frailty patients. Also, the odds ratio (OR) for frailty was determined in patients with subclinical hypothyroidism and subclinical hyperthyroidism. RESULTS: The mean age of the cases (n = 100) and controls (n = 104) was 83.2 and 78.1 years, respectively (p ≤ 0.01). The TSH levels in fragile and robust were 3.1 and 2.7 ng/ mL (p = 0.594) and the serum levels of free T4 were 1.26 and 1.32 ng/dL, respectively (p = 0.315). The OR for fragility in patients with subclinical hypothyroidism was 1.21 (CI95% 0.39-3.80, p = 0.740) and in patients with subclinical hyperthyroidism it was of 0.74 (CI95% 0.14-3.75, p = 0.714). CONCLUSIONS: There are no significant differences in serum levels of TSH or free T4 between fragile and robust patients. Subclinical hyperthyroidism and hypothyroidism were not associated with an increased risk of frailty syndrome.

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

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

Subclinical Hypothyroidism Impact on the Characteristics of Patients with Polycystic Ovary Syndrome. A Meta-Analysis of Observational Studies.

BACKGROUND/AIMS: Definitive polycystic ovary syndrome (PCOS) diagnosis should exclude thyroid dysfunctions. The purpose of the study is to examine the impact of subclinical hypothyroidism on the characteristics of PCOS patients. METHODS: A meta-analysis of the published observational studies was conducted. Medline, Scopus, and Cochrane database search was performed to identify the studies that compared euthyroid PCOS and subclinical hypothyroidism (SCH)-PCOS patients. A total of 9 studies were selected, totalizing the inclusion of 1,537 euthyroid PCOS and 301 SCH-PCOS. The data were expressed as raw mean difference and standard error, using the random-effects model. Heterogeneity among studies was examined using the Cochran's test (Q) and I2 statistics. RESULTS: Anthropometrical parameters were similar in both groups. Total cholesterol (TC) and triglyceride (TG) were higher in SCH-PCOS (p = 0.036 and p = 0.012). High-density lipoprotein cholesterol was lower in the SCH-PCOS group (p = 0.018). Fasting glucose was lower in euthyroid PCOS (p = 0.022). All androgen levels were similar in both group (p > 0.05 for all). CONCLUSION: TC, TG and fasting glucose were higher in SCH-PCOS patients. Because of the heterogeneity among studies, some summarized results should be interpreted with caution. Consistent data for future studies addressing PCOS diagnosis are provided.

Evaluation of thyroid gland as an organ at risk after breast cancer radiotherapy: a systematic review and meta-analysis.

BACKGROUND: Radiotherapy can often lead to thyroid dysfunction. Some studies demonstrated that treatment of breast cancer by RT can expose thyroid gland to high doses of radiation. The aim of this systematic review is to evaluate consideration of thyroid gland as an organ at risk. METHODS: In this systematic review and meta-analysis to select initial studies, a comprehensive search by two independent reviewers was performed. Electronical databases following: Web of Science, Google Scholar, Scopus, PubMed, Elsevier, Embase, ProQuest and Persian databases such as Iranmedex, Magiran, and SID were searched. All searches were restricted to English language between 1985 and 2017. A random effect meta-analysis is applied to estimate pooled effect size across initial studies. Funnel plot with Egger's test is used to assess potential publication bias. RESULTS: Totally, five studies (478 samples) were included in meta-analysis. The meta-analyses of result showed that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy (z = 2.68, P = 0.007). The pooled estimate of difference mean for TSH was 0.90 (95% CI 0.24, 1.55). In studies among patients with breast cancer RT, hypothyroidism was reported more than other thyroid disorders. There was not showed possibility publication bias among studies (P > 0.05). CONCLUSION: This study demonstrated that thyroid gland is affected by radiotherapy significantly and the TSH increased after radiotherapy. Protecting thyroid gland during radiation and follow-up of patients with breast cancer RT are suggested for the assessment of thyroid gland dysfunction.

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.