High-normal Thyroid-stimulating Hormone Research Articles

Association of pro-atherogenic risk factors with thyroid-stimulating hormone level in women 25–44 years old

Thyroid hormones play an important role in regulating metabolism. A large body of literature suggests an increased risk of developing metabolic syndrome (MS) in individuals with hypothyroidism, but little data exists on the effects of high-normal levels of thyroid-stimulating hormone (TSH) on metabolism.Material and methods. The study was conducted on a representative sample of people aged 25–44 years (n = 1513, of which 840 were women). The analysis included the results of 343 women. A questionnaire, anthropometric and biochemical study were carried out. Biochemical parameters were analyzed in quartiles of TSH content. Determination of MS was carried out using the criteria of NCEP ATP III (2001), IDF (2005), VNOK (2009).Results. TSH content in the examined sample was 1.5 [1.0; 2.2] mU/l (median [lower quartile; upper quartile]). Among women 25–44 years old, women with highly normal TSH level (3.1 [2.7, 3.8] mU/l) have less favorable metabolic parameters. MS was detected in 31 % cases, with a predominant increase in the frequency of abdominal obesity – in 51 %, with increased triglyceride levels in 18 %. Women with hypertriglyceridemia had higher TSH content than those with normal triglyceride levels (2.4 ± 1.6 vs. 1.8 ± 1.3 mU/L, respectively, p = 0.007).Conclusions. In women 25–44 years of age, high-normal TSH content is more often associated with metabolic unhealth.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case–control study

BackgroundIt is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3–2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3–4.3 mIU/L). MethodsThis was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n =40), healthy subjects with high-normal target TSH (n =40), subjects with treated hypothyroidism with low-normal target TSH (n =40), and subjects with treated hypothyroidism with high-normal target TSH (n =40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. ResultsSubjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P=0.013). However, serum fT4 levels were found to be significantly different between the study groups (P=0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. ConclusionVariation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

Changes in thyroid function and evolution of subclinical thyroid disease in older men.

Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

Relationship of Thyroid Function with Metabolic Parameters in Euthyroid Adults

Objective: Thyroid hormones have a significant effect on carbohydrate, lipid metabolism disorders, and insulin resistance (HOMA-IR) development. Vitamin D (25(OH)D) has been shown also can affect not only the musculoskeletal system, but also almost all tissues in the body, including the thyroid in recent years. In the study, we aim of this study is to investigate the relationship between the levels of thyroid-stimulating hormone (TSH) within the reference range and metabolic parameters in adults. Methods: 561 adult outpatients were divided into 2 groups low normal range (0.27-2.5 mIU/mL) and high normal range (2.5-4.2 mIU/mL) according to TSH, and HOMA-IR, 25(OH)D, and lipid levels were compared. Results: A statistically significant positive correlation was found between TSH and HOMA-IR in both the low normal range group (r = 0.123, p = 0.041) and the high normal range group (r = 0.196, p = 0.001). In the high normal range group, the relationship between TSH with vitamin D (r =-0.200, p =0.003), cholesterol (r =0.143, p =0.024), LDL cholesterol (r =0.154, p =0.018), non-HDL cholesterol (r = 0.134, p = 0.035) levels was statistically significant. Conclusion: Our study shows that high normal TSH levels in euthyroid adults are related to higher insulin resistance and lower 25(OH)D levels, and this interaction is a major contributor to dyslipidemia. Thyroid hormones explain the metabolic disorder in the early stages of T2DM. Therefore, we believe that screening TSH levels and determining the optimal TSH target will be beneficial.

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes

BackgroundEvidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes.MethodsThis prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39–1.30 mIU/L; medium-normal, 1.30–2.09 mIU/L; high-normal, 2.09–4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality.ResultsDuring a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07–1.61) and CVD (1.52; 1.08–2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12–1.73) and CVD (1.69; 1.17–2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants.ConclusionLow- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Comparison of reproductive outcomes in subclinical hypothyroidism women with high-normal versus low-normal thyroid-stimulating hormone levels after treatment with levothyroxine.

Reproductive outcomes in euthyroid women with high-normal thyroid-stimulating hormone (TSH) levels are comparable to those in euthyroid women with low TSH levels; however, few studies have investigated whether strictly controlled TSH levels after levothyroxine (LT4) treatment impair reproductive outcomes in infertile women with subclinical hypothyroidism (SCH). This study aimed to investigate the impact of high-normal versus low-normal TSH levels on reproductive outcomes in women undergoing their first in vitro fertilisation and embryo transfer (IVF-ET) cycle. This was a retrospective cohort study. Patients were divided into low-normal (TSH < 2.5 mIU/L, and ≥0.27 mIU/L) and high-normal (TSH ≥ 2.5 mIU/L, and <4.2 mIU/L) groups based on TSH levels after LT4 treatment. TSH levels after LT4 treatment and before ovarian stimulation were recorded. Reproductive outcomes were compared between the low-normal and high-normal TSH groups and between the euthyroid and LT4-treated groups. A total of 6002 women, 548 of whom were LT4-treated women, were finally included in this study. Among the LT4-treated women, 129 women had low-normal TSH levels, and 167 women had high-normal TSH levels. The clinical pregnancy rate, miscarriage rate, and live birth rate were comparable between the low-normal and high-normal groups (all p > .05). When adjusted by age, anti-Mullerian hormone (AMH) levels, infertility duration, transferred embryos, and dose and duration of LT4 treatment, high-normal TSH levels neither significantly decreased miscarriage (adjusted odds ratio [aOR] = 2.27, 95% confidence interval [CI] = 0.77-6.69, p = .14) nor increased clinical pregnancy (aOR = 1.15, 95% CI = 0.70-1.89, p = .57 or live birth (aOR = 0.97, 95% CI = 0.60-1.59, p = .92). Similar obstetric outcomes were observed between the low-normal and high-normal TSH groups after LT4 treatment and between the euthyroid and LT4-treated groups (all p ≥ .05). High-normal TSH levels did not have adverse effects on clinical and obstetric outcomes when compared with low-normal TSH levels after LT4 treatment. However, whether it is appropriate to set 2.5 mIU/L as the goal of treatment before IVF/ICSI remains to be determined in further well-designed studies.

Economic and Cardiometabolic Risk Factors Are Predictors of Lower Thyroid Stimulating Hormone (TSH) Levels in Hispanic/Latinx Adults with Euthyroidism-A Community-Based Study.

Thyroid hormone abnormalities are among the most common endocrine disorders comorbidly suffered alongside metabolic syndrome and type 2 diabetes mellitus (T2DM), and within the euthyroid range they may also impact other outcomes, such as mood disorders. This study aimed to observationally examine the relationship between TSH and social determinants of health and clinical measures in a euthyroid Hispanic/Latinx patient sample with a diagnosis of anxiety and/or depression disorders from a community health clinic. A needs assessment was completed using a random sample of 100 de-identified medical records of individuals who received free medical care, including mental health, at a community-based clinic. Those with low normal TSH (<2 mIU/L) compared with high normal TSH (≥2 mIU/L) had a greater odds of food insecurity (p = 0.016) and being at 100% of the federal poverty level (p = 0.015). The low normal TSH group had significantly higher fasting glucose (p = 0.046), hemoglobin A1c (p = 0.018), and total cholesterol (p = 0.034) compared with the high normal TSH group. In those with T2DM, individuals with low normal TSH had six-times greater odds of having high fasting glucose (p = 0.022) and high hemoglobin A1c (p = 0.029). These relationships warrant further study, to inform future public health policies and follow-up care for underserved and vulnerable communities.

Thyroid function and age-related decline in kidney function in older Chinese adults: a cross-sectional study

BackgroundThyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults.MethodsA total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using β value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid.ResultsIn the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (β = -0.081) and decreasing FT3 (β = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10–4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47–4.81 pmol/L, 27.6% for those with FT3 of 4.82–5.20 pmol/L, and 34.9% for those with FT3 of 5.21–6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function.ConclusionsThis study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

Worse Outcomes in Patients With Depression Linked to Low Thyroid Hormones

Worse Outcomes in Patients With Depression Linked to Low Thyroid Hormones

Thyroid-stimulating hormone levels in euthyroid patients 8 years following bariatric surgery

BackgroundBariatric surgery (BS) was shown to promote a decline in thyroid-stimulating hormone (TSH) in euthyroid patients with severe obesity in the short-term. Aim of the present study was to assess the effect of weight loss on thyroid function in euthyroid patients in the long-term following different bariatric procedures.MethodsIn a retrospective cohort study including 135 patients at baseline, thyroid function was assessed at six time points up to 8 years after surgery. Patients were stratified by TSH levels at baseline and divided into two groups to compare the change in TSH at long-time. We used log-linear regression to assess the relation between thyroid hormones and TSH and linear regression analyses to identify variables that were thought to determine TSH and fT3/fT4-ratio as well as their change long-term.ResultsOver a mean follow-up of 8 years, TSH and fT3/fT4-ratio declined (both p < 0.001). Patients with high-normal TSH showed a greater decline in TSH than those with normal TSH compared to baseline. Thyroid hormones and TSH displayed a negative log-linear correlation at long-term follow-up. Change in TSH at long-time showed a negative correlation with TSH at baseline (B = −0.55; p < 0.001). With regard to type of surgery, there were no significant differences in TSH.ConclusionBS promotes a decline of TSH in euthyroid patients up to 8 years after intervention despite weight regain. The greatest change in TSH was seen among patients with high-normal baseline-TSH. Results of log-linear regression suggest recovery of the pituitary-thyroid axis. Type of surgery did not affect the change in TSH levels over time.

Thyroid function and IVF outcome for different indications of subfertility.

Graphical Studies evaluating pregnancy outcomes after assisted reproductive treatment (ART) in women with high-normal (2.5–4.5 mIU/L) thyroid-stimulating hormone (TSH) levels are conflicting, possibly due to different patient charactistics and subfertility indications. The aim of this study was to examine the hypothesis that high-normal compared to low-normal TSH levels are associated with adverse implications for pregnancy outcomes in conventional in vitro fertilization (IVF)-treated women. Therefore, we analyzed retrospectively the characteristics and pregnancy outcomes of 949 subfertile women with TSH 0.3–4.5 mIU/L, treated with conventional IVF between January 2008 and March 2012. Demographic and baseline characteristics were compared between groups of patients based on TSH quartiles, using one-way Anova, Kruskal–Wallis ANOVA and chi-square test. Women with high-normal quartile TSH were significantly more likely to be primary subfertile (P = 0.01), with a higher prevalence of unexplained subfertility and with 15% fewer live births after IVF compared to lower TSH quartiles (P = 0.02). In secondary subfertile women with high-normal TSH, male factor subfertility prevailed (P = 0.01), with more live births (P = 0.01). When analyzing primary and secondary subfertile women as one group, these differences failed to be observed, showing no differences in cumulative pregnancy outcomes of IVF between TSH quartiles (I: 0.3–1.21 mIU/L; II: 1.22–1.68 mIU/L; III: 1.69–2.31 mIU/L; IV: 2.32–4.5 mIU/L). In conclusion, primary subfertile women predominate in the high-normal TSH quartile, associated with significantly fewer live births in a subgroup of primary unexplained subfertile women (9%; n = 87/949), while in secondary subfertile women, dominated by male factor subfertility, high-normal TSH is associated with more live births.Lay summaryThyroid hormones are required for all cell processes in the body. An underactive thyroid gland, in which insufficient thyroid hormones are produced and thyroid-stimulating hormone (TSH) rises, is associated with a lower chance of pregnancy. It is not yet clear above which TSH level, 4.5 or also 2.5 mIU/L, this lower probability occurs. Therefore, in 949 couples treated with conventional IVF, we examined whether high-normal TSH levels (TSH: 2.5–4.5 mIU/L) compared to low normal TSH levels (0.3–2.5 mIU/L) affect the live birth rate. We found that women who were trying to become pregnant for the first time, especially without any other cause, that is unexplained subfertility, were more likely to have higher TSH levels. These women had a much lower chance of having a baby compared to women with low-normal TSH levels.

The Association between Thyroid-Stimulating Hormone and Long-Term Outcomes in Patients with ST Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

ObjectiveThyroid hormones are closely related to the cardiovascular system. Our study aimed to explore the impact of admission thyroid-stimulating hormone (TSH) levels on long-term outcomes in patients with acute ST segment elevation myocardial infarction (STEMI) by detailed stratifications of TSH.MethodsConsecutive STEMI patients admitted to our hospital were divided into four groups: Group 1 (TSH <0.35 mIU/L), Group 2 (TSH 0.35–1.0 mIU/L), Group 3 (TSH 1.0–3.5 mIU/L), and Group 4 (TSH >3.5 mIU/L). The primary endpoint was all-cause mortality during follow-up, and the median follow-up was 2.5 years. Cox proportional hazard regression models were performed to identify the prognostic value of TSH.ResultsA total of 1186 patients were included. Group 4 was presented with higher systolic and diastolic blood pressure (all P < 0.001), and Group 1 had more patients complicated by heart failure (Killip class >I, P = 0.014). During follow-up, 138 deaths occurred. Patients in Group 4 had the worst long-term outcomes (P < 0.001). The cumulative survival in Group 4 was remarkably lower (Log rank P < 0.001), whereas the other three groups were comparable (Log rank P = 0.365). Through Cox regression analysis, only TSH >3.5 mIU/L was identified as an independent risk factor for long-term mortality after STEMI.ConclusionOnly TSH elevation beyond the normal range was associated with worse long-term prognosis in STEMI patients, while high-normal TSH or reduced TSH did not alter long-term prognosis of STEMI patients. TSH >3.5 mIU/L was an independent risk factor for long-term mortality in STEMI.

Фактори кардіоваскулярного ризику у хворих на артеріальну гіпертензію при різному рівні тиреотропного гормону

Метою роботи було встановити вплив рівня тиреотропного гормону (ТТГ) на частоту і вираженість факторів кардіоваскулярного ризику у хворих на артеріальну гіпертензію (АГ). Були обстежені 123 хворі із АГ I–II ступенів віком 45–70 років. Методи дослідження: визначення показників ліпідограми, ТТГ, вільного тироксину, ехокардіографія, вимірювання офісного артеріального тиску (АТ), дуплексне сканування судин шиї, тестування за госпітальними шкалами тривоги і депресії. Серед обстежених хворих 12,4 % мали не діагностований раніше субклінічний гіпотиреоз, що асоціювався з більшою частотою дисліпідемії, порушення вуглеводного обміну, гіпертрофії лівого шлуночка і атеросклеротичного ураження сонних артерій, більш високими значеннями пульсового АТ, а також зі зменшенням швидкості клубочкової фільтрації і тривожно-депресивними розладами. При аналізі групи з нормальною функцією щитоподібної залози (ЩЗ) було виявлено, що високонормальний рівень ТТГ (2–4 мОд/л) також пов’язаний зі збільшенням частоти факторів кардіоваскулярного ризику і погіршенням стану органів-мішеней порівняно з особами із низьконормальним рівнем ТТГ. Отже, функціональний стан ЩЗ впливає на частоту та вираженість факторів ризику і уражень органів-мішеней при АГ, що потребує ретельного його контролю у хворих із кардіологічною патологією.

More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels

Objectives: The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. Design: This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and χ² test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The χ² test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. Results: Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. Limitations: Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. Conclusions: The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.

Influence of thyroid-stimulating hormone on the recurrence after radiofrequency ablation for atrial fibrillation

Atrial fibrillation is one of the most common sustained disorders of cardiac rhythm and is associated with an increased risk of mortality, morbidity due to thromboembolic complications, and heart failure. It is important to highlight that the causative factors are vast. It is well-known that thyroid dysfunction has a proarrhythmic effect and increases the risk of cardiovascular disease. Hyperthyroidism or thyrotoxicosis is recognized to be a baseline risk factor for the development of atrial fibrillation. However, the role of hypothyroidism in atrial arrhythmogenesis is less recognized and not fully understood. At the moment radiofrequency catheter ablation is actively used in the treatment of atrial fibrillation, which in most cases has high efficiency and persistent effect. Despite that, the recurrence of supraventricular tachyarrhythmia can be observed in some patients even after radiofrequency catheter ablation. Patients with a history of hypothyroidism or even high-normal thyroid-stimulating hormone levels are more likely to have a recurrence of supraventricular tachyarrhythmia after radiofrequency catheter ablation. Therefore, thyroid-stimulating hormone levels should be determined in patients who have undergone radiofrequency catheter ablation of atrial fibrillation, especially paroxysmal atrial fibrillation. Consequently, it should be noted that the assessment and correction of modifying risk factors before radiofrequency catheter ablation may provide opportunities for future prevention of recurrence of supraventricular paroxysmal arrhythmias, improve the prognosis and overall quality of life in patients of this group. We have demonstrated the clinical case and emphasized the association of high-normal thyroid-stimulating hormone levels with supraventricular tachyarrhythmia recurrence after radiofrequency catheter ablation for atrial fibrillation.

SAT-447 Thyroid Function, Cardiovascular Disease, and Mortality: A Mediation Analysis

Background: Subclinical hypothyroidism is a common clinical entity among the United States (U.S) adults and has been associated with increased risk of cardiovascular disease (CVD) and mortality in some studies. However, the mediation effect of CVD from elevated serum thyroid stimulating hormone (TSH) to mortality has not yet been well established or sufficiently quantified. In this study, we aimed to elucidate the extent to which subclinical hypothyroidism or high-normal thyroid stimulating hormone [TSH] concentrations (i.e. upper normative-range TSH concentrations) contribute to mortality through its effect on CVD among U.S. adults. Methods: This study relies on the U.S. representative samples of 9,020 adults enrolled in the National Health and Nutrition Examination Surveys (NHANES) 2001-2002, 2007-2012 and their mortality data through 2015. We employed Cox proportional hazards regression models to investigate associations between the TSH concentration categories (subclinical hypothyroidism or tertiles of serum TSH concentrations within the reference range) and all-cause mortality. Utilizing mediation analysis within the counterfactual framework, we estimated the mediation effect of CVD on the association between TSH and all-cause mortality. Results: The median duration of follow-up for mortality ascertainment was 7.3 (interquartile range, 5.4–8.3) years, during which 435 deaths from all causes were identified. Subjects with TSH in the subclinical hypothyroidism and the high-normal TSH tertile concentrations were associated with increased all-cause mortality (subclinical hypothyroidism: hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.14–3.19; high-normal TSH: HR, 1.36; 95% CI, 1.07–1.73) compared with the middle-normal TSH tertile concentration. CVD mediated 14.3% and 5.9% of the effects of subclinical hypothyroidism and high-normal TSH on all-cause mortality, respectively, with the CVD mediation effect being most pronounced in women and subjects ≥60 years old. No mediation through CVD was found for low-normal TSH levels and all-cause mortality. Conclusion: CVD mediated the effects of subclinical hypothyroid and high-normal TSH concentrations on all-cause mortality in the U.S. general population. These findings may have potential implications for treatment, and early and more aggressive CVD screening for such at risk populations. Further studies are needed to examine the clinical impact of targeted therapy towards mid-normal TSH concentration.

Obese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy Expenditure

Obese Women With Hypothyroidism Treated with Levothyroxine Have Reduced Resting Energy Expenditure

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD

AimWe aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. Materials and methodsWe enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a ‘strict-normal’ TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a ‘high-normal’ TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. ResultsCompared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298–8.284; P=0.012). ConclusionIn euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.