High Free Triiodothyronine Research Articles

Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis.

Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2=0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Registered number in PROSPERO: CRD42023405052.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

The relationship between serum superoxide dismutase and thyroid function in obese patients after Laparoscopic sleeve gastrectomy

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity (n = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n = 112) and high levels of SOD (HSOD, n = 107) according to the median value of SOD levels (183 U/mL). SOD and thyroid hormones were measured and compared at baseline, 3, 6, and 12 months after LSG. The HSOD group had lower body mass index (BMI), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) than the NSOD group (p < 0.001, p = 0.031, p < 0.001, respectively). However, they had higher free triiodothyronine (FT3) and free thyroxine (FT4) (p = 0.019 and p = 0.017, respectively). SOD was significantly negatively associated with TSH and positively associated with FT4. Of all the patients, 22.31% (NSOD: 66.67%; HSOD: 33.33%) had subclinical hypothyroidism (SH), and there were lower SOD levels in the SH group. Preoperative SOD was a protective factor for SH. After LSG, SOD and FT4 levels were increased at 12 months after LSG, however, TSH, FT3, total triiodothyronine (TT3) and TT4 levels decreased compared to the preoperative levels at 3, 6, and 12 months in the SH group. Postoperative changes in FT4 and TT4 levels correlated with changes in SOD levels. SOD, which is correlated with thyroid hormones, protects against SH in patients with obesity. The improvement in thyroid function with SH after LSG may be related to increased SOD levels.

High free triiodothyronine, and free-triiodothyronine-to-free-thyroxine ratio are associated with metabolic syndrome in a euthyroid employee population: the Zhejiang Zhenhai study.

The aim of this study was to elaborate the link of thyroid hormones (THs) and metabolic syndrome (MetS) in a Chinese euthyroid employee population with MetS component(s). An annual health checkup was performed on employees in 2019. Anthropometric parameters, metabolic parameters, and thyroid function were measured. A questionnaire was used in conjunction with Zhenhai Lianhua Hospital database to receive employees' medication records and thyroid surgical history records. A total of 5486 eligible employees were included; the prevalence of MetS was generally higher in males than in females (38.9 vs. 30.4%, P < 0.001). Among employees with central obesity, hypertriglyceridemia, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), the prevalence of MetS was 68.8, 63.6, 68.2, 48.8, and 60.0% in males and 72.6, 63.3, 61.3, 42.3, and 42.3% in females, respectively. Logistic regression analysis showed that thyroid-stimulating hormone and free thyroxine (FT4) quartiles had no significant impact on MetS. Free triiodothyronine/free thyroxine (FT3/FT4) and free triiodothyronine (FT3)) quartiles were positively associated with the increased odds ratio (OR) for MetS and dyslipidemia (hypertriglyceridemia and low HDL-C), regardless of gender. In males, FT3 and FT3/FT4 quartiles were positively associated with the OR for central obesity, whereas FT4 quartiles were negatively associated; both FT3 and FT4 quartiles were positively associated with increased OR of hyperglycemia, while similar results were not observed in females. Interaction analysis indicated no significant effect of gender and TH interactions on risk of MetS. High FT3 and FT3/FT4 were strongly linked with MetS and dyslipidemia in our study, even in the euthyroid individuals. Tighter control of thyroid function was necessary for those with preexisting MetS component(s).

Can Mild-to-Moderate Iodine Deficiency during Pregnancy Alter Thyroid Function? Lessons from a Mother-Newborn Cohort.

Severe iodine deficiency during pregnancy has substantial hormonal consequences, such as fetal brain damage. Data on the potential effects of mild-to-moderate iodine deficiency on the thyroid function of pregnant women and their newborns are scarce and divergent. We investigated the association between iodine intake in pregnancy and maternal and neonatal thyroid function in a region with mild-to-moderate iodine deficiency. Pregnant women’s iodine status was evaluated using an iodine food frequency questionnaire, serum thyroglobulin (Tg), and urinary iodine concentration (UIC). Neonatal thyrotropin (nTSH) values were measured after birth. Obstetrics and anthropometric data were also collected. Among the 178 women (median age 31 years) included in the study, median (interquartile range) estimated dietary iodine intake, Tg and UIC were 179 (94−268) μg/day, 18 (11−33) μg/L, and 60 (41−95) μg/L, respectively. There was a significant inverse association of iodine intake with Tg values among the study population (β = −0.2, F = 7.5, p < 0.01). Women with high free triiodothyronine (FT3) values were more likely to exhibit an estimated iodine intake below the estimated average requirement (160 μg/day, odds ratio [OR] = 2.6; 95% confidence interval [CI], 1.1−6.4; p = 0.04) and less likely to consume iodine-containing supplements (OR = 0.3, 95% CI, 0.1−0.8; p = 0.01). It is possible that thyroid function may be affected by iodine insufficiency during pregnancy in regions with mild-to-moderate iodine deficiency. The relatively small sample size of the studied population warrants further investigation.

FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007-2012.

BackgroundThyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population.MethodsThis retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.ResultsDuring a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results.ConclusionsFT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population.

Улучшение исходов ишемического инсульта у пациентов с высоким уровнем свободного трийодтиронина по сравнению с пациентами с гипо- и эутиреозом

Актуальность. Известно, что дисфункция щитовидной железы ассоциирована с повышенным риском развития цереброваскулярных заболеваний. Однако накопленные в течение последних лет экспериментальные данные свидетельствуют о том, что гормоны щитовидной железы могут иметь определенные нейропротекторные эффекты. Цель исследования: определить взаимосвязь между уровнем свободного трийодтиронина в дебюте острого ишемического инсульта и функциональным исходом инсульта через 6 месяцев. Материалы и методы. В исследование был включен 121 пациент с впервые развившимся острым ишемическим инсультом. Концентрации свободного трийодтиронина (свT3), свободного тироксина (свT4), тиреотропного гормона и наличие базисных факторов риска инсульта оценивались в течение 24 часов с момента появления симптомов. Неврологический дефицит оценивался по Скандинавской шкале инсульта (SSS). Неблагоприятный функциональный исход определялся как показатель mRs ≥ 3 баллов через 6 месяцев после перенесенного инсульта. Результаты. Тест ANOVA показал, что пациенты с уровнем свT3 в 4-м квартиле (≥ 5,35 пмоль/л) имели значительно более тяжелый неврологический дефицит по сравнению с пациентами с уровнем свТ3 во 2–3-м квартилях (медиана SSS 48 баллов против 37 баллов, p = 0,0481) и особенно по сравнению с пациентами с уровнем свТ3 в 1-м квартиле (≤ 3,4050 пмоль/л, медиана SSS 48 против 30, p = 0,0018). Согласно тесту Краскала — Уоллиса, пациенты с уровнем свободного Т3 выше 75-го процентиля имели более благоприятный функциональный исход со средним значением по модифицированной шкале Рэнкина 2,5 балла по сравнению с пациентами с уровнем свT3 в 25–75-м процентилях (со средним значением по модифицированной шкале Рэнкина 4 балла). Результаты анализа пробит-регрессии свидетельствуют о дозозависимом влиянии уровня свT3 на вероятность благоприятного исхода инсульта. Уровень свободного Т3 6,56 пмоль/л был связан с 50% вероятностью благоприятного исхода, а уровень свободного Т3 выше 8,67 пмоль/л был ассоциирован с 75% вероятностью благоприятного исхода инсульта. Выводы. Исследование показало, что пациенты с высоким уровнем свободного трийодтиронина при дебюте ишемического инсульта имеют более благоприятный функциональный исход, даже по сравнению с пациентами с нормальным уровнем свободного Т3. Более высокие уровни свободного трийодтиронина также ассоциируются с менее тяжелым неврологическим дефицитом в острой фазе. Выявлено дозозависимое влияние уровня свободного трийодтиронина на вероятность благоприятного исхода инсульта. Полученные данные свидетельствуют о том, что тиреоидный профиль является не только фактором, влияющим на течение ишемического инсульта, но и потенциальной мишенью для терапевтической коррекции.

Metastatic choriocarcinoma in a young woman presenting as thyroid storm: a\xa0case report

BackgroundThyroid storm is an endocrine emergency and life-threatening condition discovered in 1926. There is no specific laboratory parameter that can differentiate or distinguish between thyroid storm and primary hyperthyroidism. Diagnosis is made on a clinical scoring system, including the Burch–Wartofsky point scale and Japanese Thyroid Association scoring system. The management is early diagnosis, immediate initiation of anti-thyroid medications, intensive care monitoring, and prevention of multiorgan failure.Case presentationA 30-year-old Pakistani female presented with complaint of headache, vomiting, and generalized weakness for 3 weeks. She had an episode of seizure-like activity at home, and so was rushed to the emergency department. A detailed thyroid examination revealed a soft, nontender gland with no enlargement or bruit and no exophthalmos. Her thyroid-stimulating hormone was extremely low, with high free triiodothyronine and thyroxine. Thyroglobulin was 425 ng/ml (normal reference range ≤ 55 ng/ml), and thyroid-stimulating hormone receptor antibody was 0.87 IU/L (normal reference range 0–1.75 IU/L). She had high levels of beta-human chorionic gonadotropin hormone on initial presentation. Transvaginal ultrasound showed no intrauterine pregnancy, but an echogenic focus was found adherent to the right ovary with no vascularity. With the chief complaint of headache, she underwent magnetic resonance imaging of the brain that showed multiple scattered hemorrhagic lesions in supratentorial and infratentorial brain parenchyma that were highly suspicious for metastases. Computed tomography scan of the chest, abdomen, and pelvis revealed multiple neoplastic lesions in the lung, liver, spleen, and kidneys. A Tru-Cut liver biopsy showed linear cores of liver tissue with metastatic carcinoma with morphological features consistent with choriocarcinoma. Our patient scored 65 on the Burch–Wartofsky point scale. As per the Japanese Thyroid Association scoring system, our patient met the criteria for a “definite thyroid storm.” She had initiated propranolol to achieve adequate control of her heart rate and dexamethasone. Carbimazole was started to control her thyroid function. Her thyroid function after 2 weeks of treatment showed significant improvement. Methotrexate and etoposide were given for choriocarcinoma. She made a good recovery and was discharged home. She will undergo rehabilitation along with ongoing chemotherapy (methotrexate and etoposide weekly till beta-human chorionic gonadotropin levels normalize). Unless her source of beta-human chorionic gonadotropin is carefully under control, she will continue to take anti-thyroid medications.ConclusionChoriocarcinoma is not only associated with hyperthyroidism but can induce thyroid storm. Beta-human chorionic gonadotropin is directly associated with promoting thyroid dysfunction. Patients with gestational trophoblastic disease should be under close surveillance to prevent thyroid storms.

Impact of maternal thyroid hormone in late pregnancy on adverse birth outcomes: A retrospective cohort study in China.

The purpose of this study was to explore the impact of maternal thyroid hormone dysfunction in late pregnancy on birth outcomes in a Chinese population. We retrospectively examined hospitalisation records and laboratory data between April 2016 and March 2017 and obtained results from 11,564 consecutive pregnant women with singleton births in which serum thyroid hormone had been examined together with birth outcomes. We assessed the association between maternal thyroid level and dysfunction with adverse birth outcomes based on regression analysis. Hyperthyroidism was associated with an increased risk of preterm birth (PTB, adjusted OR: 2.41, 95% CI: 1.83-3.17) and hypothyroidism was associated with an increased risk of small for gestational age (SGA, adjusted OR: 1.56, 95% CI: 1.10-2.22), while hyperthyroxinaemia was associated with a decreased risk of large for gestational age (LGA, adjusted OR: 0.64, 95% CI: 0.45-0.90). In addition, compared to women with normal FT3 and TSH (≥the 5th and ≤the 95th percentiles), women with high free triiodothyronine (FT3 >the 95th percentile) and low thyroid-stimulating hormone (TSH <the 95th percentile) had a 4.02- fold higher risk of PTB (95% CI: 2.05-7.88), and women with low FT3 and high TSH had a 4.22- fold greater risk of SGA (95% CI: 1.59-11.23). Our study supports associations between multiple types of maternal thyroid dysfunction in late pregnancy and adverse birth outcomes.

Thyroid function and risk of all-cause and cardiovascular mortality: a prospective population-based cohort study

PurposeAlthough thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality.MethodsWe included community-dwelling individuals aged 28–75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors.ResultsMean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92–1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00–1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56–1.06). Higher free thyroxine (FT4) was associated with all-cause mortality (1.18, 1.07–1.30) and with cardiovascular mortality only in elderly (1.61, 1.19–2.18), but not in younger participants (1.03, 0.78–1.34). Higher free triiodothyronine (FT3) was associated with all-cause mortality in females only (1.18, 1.02–1.35). FT3 was not associated with cardiovascular mortality (0.91, 0.70–1.18).ConclusionsCommunity-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function.

Higher free triiodothyronine concentration is associated with lower prevalence of microangiopathic complications and better metabolic control in adult euthyroid people with type 1 diabetes

PurposeType 1 diabetes mellitus (T1DM) is a disorder of insulin deficiency but with a wide range of hormones simultaneously disturbed. The study was performed to explore relation of free triiodothyronine (FT3) with metabolic control and occurrence of microangiopathic complications.MethodsA total of 266 adult T1DM participants [56% men; 32 (interquartile range, IQR: 25–39) years and disease duration 13 (IQR: 8–19) years] in euthyroid state with negative history for hypothyroidism were included to the study. Participants were screened for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and FT3. Moreover, microangiopathic complications (retinopathy, diabetic kidney disease, peripheral and autonomic neuropathy), markers of metabolic control such as glycated hemoglobin (HbA1c) were evaluated.ResultsA total of 114 (42.9%) people had diagnosed at least one microangiopathic complication. In multivariable linear regression higher HbA1c was statistically significant independent predictor of lower FT3 (β = −0.25; p < 0.0001) after adjustment for sex, T1DM duration, HbA1c, waist-to-hip ratio (WHR) (R2 = 0.15, p < 0.0001). Higher FT3 was simultaneously a predictor of lower prevalence of microangiopathy in multivariate logistic regression analysis (odds ratio, 0.51; 95% confidence interval, 0.27–0.98; p = 0.04) after an adjustment for: age, hypertension, HbA1c, WHR and total cholesterol (TC).ConclusionsFT3 as tissue active hormone plays a clinically important role in T1DM people. The higher FT3 concentration is related to the lower prevalence of microangiopathy and better metabolic control of the disease in adult euthyroid people with T1DM.

High free triiodothyronine and free-triiodothyronine-to-free-thyroxine ratio levels are associated with metabolic syndrome in a euthyroid population

AimsTo determine the association between free triiodothyronine (FT3), free thyroxine (FT4) and free-triiodothyronine-to-free-thyroxine ratio (FT3/FT4) levels and Metabolic Syndrome (MetS). Materials and methodsWe carried out an analytical cross-sectional study in euthyroid adults of both sexes, who attended the outpatient service of a private clinic in Lima-Peru during the 2014–2016 period. Participants were divided into tertiles (low, intermediate and high) according to their FT3, FT4, and FT3/FT4 ratio values. MetS was defined when three or more metabolic criteria were met by the participants. ROC curves were constructed, and Youden’s Index were used to identify the optimal cut-points of each thyroid marker. We elaborated crude/adjusted Poisson regression models to evaluate the association between the thyroid markers and the presence of MetS. The reported association measure was the prevalence ratio (PR) with their respective 95% confidence intervals (95% CI). ResultsWe analyzed 245 participants, the average age was 38.5 ± 10.3 years, 29.8% were males, and the prevalence of MetS was 31%. In the adjusted Poisson regression models, the prevalence of MetS was higher among the high FT3 tertile compared to the low tertile (aPR = 2.01; 95% CI: 1.22–3.34). The prevalence of MetS was higher among the intermediate FT3/FT4 ratio tertile and the high FT3/FT4 ratio tertile compared to the low tertile, (aPR = 1.78; 95% CI: 1.02–3.10) and (aPR = 2.80; 95% CI: 1.67–4.72); respectively. The highest areas under the curve (AUC) were found for FT3 and FT3/FT4 ratio with areas of 0.654 (95% CI: 0.58–0.73) and 0.649 (95% CI: 0.57–0.72); respectively. ConclusionElevated levels of FT3 and FT3/FT4 ratio were associated with MetS in a euthyroid population.

Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study

ObjectiveOvert hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects. MethodsThe study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5–4.0mU/L, free thyroxine (FT4) 11–19.5pmol/L and free triiodothyronine (FT3) 4.4–6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant. ResultsFLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29–1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70–0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39–1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P<0.0001). ConclusionsEuthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.

High rates of fatigue in newly diagnosed Graves' disease

Background: Fatigue in patients with Graves’ disease has rarely been addressed. Purpose: To investigate the presence of subjective fatigue as well as cognitive fatigability among patients with untreated Graves' disease. Methods: Thirty-four patients (mean age: 39.2 ± 9.8) with newly diagnosed untreated Graves' disease and 31 healthy controls (mean age 36.7 ± 8.8) were investigated. The Digit Symbol Substitution Test was used for assessment of cognitive fatigability and the Fatigue Severity Scale (FSS) and the Everyday Consequences of Fatigue (ECF) questionnaire were used to assess self-rated effects of fatigue on activities and motivation. Results: Patients scored significantly higher on self-rated fatigue impact (FSS) than controls (p < 0.001) and 56% of patients reached a clinical level of fatigue impact. Half of the patients suffered from cognitive fatigability compared to 19% of the controls (p = 0.010). High free triiodothyronine (T3) levels were associated with ECF scores. Depression was associated with self-rated fatigue impact but not with cognitive fatigability. Free T3 correlated significantly with consequences of fatigue among the fatigued patients, while free T3 correlated significantly with incidental memory among the non-fatigued patients. Conclusions: The results suggest that both subjective fatigue impact and cognitive fatigability are common in untreated Graves' disease and that thyroid hormone levels might have differential effects on fatigue impact and memory in different individuals.

Triiodothyronine and Free Thyroxine Levels are Differentially Associated with Metabolic Profile and Adiposity-Related Cardiovascular Risk Markers in Euthyroid Middle-Aged Subjects

We have previously shown that in healthy young men, a less favorable body composition is associated with higher free triiodothyronine (fT3) levels within the euthyroid range. Besides, a higher free-triiodothyronine-to-free-thyroxin (fT3-to-fT4) ratio has been related to a less favorable metabolic phenotype and more placental growth in pregnant women. In the present study, we therefore investigated whether serum thyrotropin (TSH), thyroid hormone levels, and the fT3-to-fT4 ratio are associated with metabolic and adiposity-related cardiovascular risk markers in a healthy population of middle-aged euthyroid men and women. Thyroid parameters were measured in 2524 generally healthy subjects from the Asklepios Study (35-55 years, mean age 46 years). Analyses were restricted to 2315 subjects (1138 women and 1177 men), not using thyroid medication, not having anti-TPO levels above clinical cutoff values or TSH levels outside the reference range (0.27-4.2 mU/L). Twenty-seven percent of the women and 47.5% of the men were overweight, while 13% of women and 17% of men were obese. Twenty percent of the subjects were active smokers. Serum thyroid function parameters were determined by electrochemiluminescence. fT3 and the fT3-to-fT4 ratio were positively related to body mass index (BMI), waist circumference, and components of metabolic syndrome, that is, triglycerides, systolic and diastolic blood pressure, and fasting plasma glucose, and negatively with HDL-cholesterol levels, whereas fT4 was negatively associated with BMI, waist circumference, and triglycerides (p<0.001). TSH related positively with total cholesterol levels (p<0.01), triglycerides, and systolic and diastolic blood pressure (p<0.001). The fT3-to-fT4 ratio was further positively associated with the adiposity-related inflammation markers interleukin-6 and high-sensitivity C-reactive protein and to pulse wave velocity. All associations were adjusted for sex, age, height, and smoking, and most associations persisted after additional adjustment for weight or waist circumference. In healthy euthyroid middle-aged men and women, higher fT3 levels, lower fT4 levels, and thus a higher fT3-to-fT4 ratio are consistently associated with various markers of unfavorable metabolic profile and cardiovascular risk.

Smoking and Early Pregnancy Thyroid Hormone and Anti-Thyroid Antibody Levels in Euthyroid Mothers of the Northern Finland Birth Cohort 1986

Smokers in the general population have lower thyrotropin (TSH) and higher free triiodothyronine (fT3) and free thyroxine (fT4) concentrations, but the results in pregnant population vary from no effect to a decrease in TSH and fT4 concentrations and an increase in fT3 levels. Our objective was to further evaluate the question of whether there is an association between smoking, before and during pregnancy, with maternal thyroid function during pregnancy and with the risk for subsequent hypothyroidism. Our study population was a prospective population-based cohort (N=9362), the Northern Finland Birth Cohort 1986, with extensive data throughout gestation. The mothers underwent serum sampling in early pregnancy. The samples were assayed for TSH, fT3, fT4, thyroid-peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Abs) (n=5805). Mothers with thyroid dysfunction diagnosed before or during pregnancy were excluded, leaving 4837 euthyroid mothers. The smoking status of mothers and fathers were requested by questionnaires during pregnancy. Subsequent maternal morbidity relating to hypothyroidism 20 years after the index pregnancy was evaluated using national registers. Euthyroid mothers who smoked before, or continued smoking during first trimester of pregnancy, had higher serum fT3 (p<0.001) and lower fT4 (p=0.023) concentrations than nonsmokers. Smoking in the second trimester was associated with higher fT3 (p<0.001) concentrations, but no difference in fT4 concentrations compared with nonsmokers. TG-Abs were less common among smoking than nonsmoking mothers (2.5% vs. 4.7%, p<0.001), but the prevalence of TPO-Ab was similar. Paternal smoking had no independent effect on maternal early pregnancy thyroid hormone or antibody concentrations. The risk of subsequent maternal hypothyroidism after follow-up of 20 years was similar among prepregnancy smokers and nonsmokers. In euthyroid women, smoking during pregnancy was associated with higher fT3 levels and lower fT4 levels; possibly reflecting smoking-induced changes in peripheral metabolism of thyroid hormones. No differences were found in TSH concentrations between smokers and nonsmokers. Our results differ from those of the general population, which usually have shown smoking-induced thyroidal stimulation. This is possibly due to pregnancy-induced changes in thyroid function. Decreases in fT4 levels among smokers might predispose to hypothyroidism or hypothyroxinemia during pregnancy. Despite these changes in thyroid function, smoking did not increase the woman's risk of subsequent hypothyroidism.

Weight Loss Through Gastric Banding: Effects on TSH and Thyroid Hormones in Obese Subjects With Normal Thyroid Function

Studies on thyroid function in obesity yielded inconsistent results; high thyroid-stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)-3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high-density lipoprotein-cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high-density lipoprotein-cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities.