Low Thyroid-stimulating Hormone Concentrations Research Articles

Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, and dementia risk: results from the NHANES 2011-2012 and Mendelian randomization analysis.

As the world ages, dementia places a heavy burden on society and the economy, but current methods of diagnosing dementia are still limited and there are no better therapies that target the causes of dementia. The purpose of this work is to explore the relationship between thyroid disease, thyroid stimulating hormone (TSH) concentrations, free tetraiodothyronine (FT4) concentrations and cognitive function. This study utilized cognitive function and thyroid data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between different groups of TSH and FT4 concentrations and cognitive function using weighted logistic regression and restricted cubic spline (RCS), and then used two-sample Mendelian Randomization (MR) to assess the causal relationship between hyperthyroidism, hypothyroidism, TSH and FT4 concentrations with dementia. Our analysis of the 2011-2012 NHANES data showed that the individuals with low TSH concentrations had higher Alzheimer's Disease Word List Registry Consortium1 (CERAD1) and CERAD.delay.recall scores than individuals with high TSH concentrations, and individuals with low FT4 concentrations had higher CERAD3 and Animal Fluency Test scores than individuals with high FT4 concentrations. Our results also showed a non-linear relationship between serum TSH and FT4 concentrations and the Animal Fluency Test. The TSH concentrations within the range of 1.703 to 3.145 mIU/L exhibit a positive correlation with Animal Fluency Test, whereas concentrations outside this range are negatively correlated with Animal Fluency Test. The FT4 concentrations exhibited a positive correlation with Animal Fluency Test to the left of the FT4 concentrations inflection point (0.849 ng/L), whereas to the right of this inflection point, correlation was negative. MR analysis results further indicate that genetic predisposition to hyperthyroidism may be associated with a reduced risk of dementia and vascular dementia(VaD). Conversely, genetic predisposition to hypothyroidism appears to be linked with an increased risk of dementia and VaD. Additionally, genetic predisposition to elevated TSH concentrations may be correlated with a heightened risk of risk of Alzheimer's disease (AD). This study provides evidence of a nonlinear relationship between TSH and FT4 concentrations and cognitive function, with hyperthyroidism decreasing the risk of dementia and VaD, hypothyroidism increasing the risk of dementia and VaD, and elevated serum TSH concentrations increasing the risk of AD. Furthermore, prioritizing early detection, diagnosis, and treatment through the assessment of thyroid function in individuals at high risk for developing dementia is of paramount importance. This strategy has the potential to significantly contribute to the prevention and deceleration of dementia progression.

The influence of calibration on bias in quality control and patient results for TSH on Vitros XT 7600 analyzer.

Thyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients' samples. In the period from October 2021 to August 2022 we looked at the QC results of ten 28-days' calibration time intervals and calculated relative bias compared to the mean. For each time interval the mean from three QC points before and after calibration was calculated. The average from 10 pre- and post-calibration means was calculated and the relative bias, pre- and post-calibration, was then calculated. We used 5 patient samples with low, normal and high TSH concentrations and calculated relative bias pre- and post-calibration. The allowed relative bias for TSH is ± 6.7%. At both QC levels, with the respective means of 5.14 mIU/L (coefficient of variation, CV% = 3.1%) and 27.80 mIU/L (CV% = 3.2%) had their respective relative bias - 8.2% and - 7.9%. The patient samples with low (0.586 mIU/L), normal (2.89 mIU/L and 5.19 mIU/L) and high (20.5 mIU/L and 39.8 mIU/L) TSH had - 4.1%, - 4.0%, - 3.5%, - 5.1% and - 4.1%, respectively. Even though the relative bias exceeded allowable criteria for the QC samples, this was not manifested on the patients' samples.

Evaluation of a novel, sensitive thyroid-stimulating hormone assay as a diagnostic test for thyroid disease in cats.

Clinicians commonly use thyroid-stimulating hormone (TSH) concentrations to diagnose thyroid disorders in humans and dogs. In cats, canine TSH chemiluminescent immunoassays (CLIA) assays are commonly used to measure TSH, but these TSH-CLIAs cannot measure low TSH concentrations (< 0.03 ng/mL) and therefore cannot distinguish between low-normal concentrations and truly low TSH concentrations (characteristic of hyperthyroidism). Our aim was to evaluate a novel TSH assay based on bulk acoustic wave (BAW) technology that has lower functional sensitivity (0.008 ng/mL) than TSH-CLIAs. 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. Serum concentrations of T4, TSH-CLIA, and TSH-BAW were measured in all cats. Untreated hyperthyroid cats were divided into 4 severity groups (subclinical, mild, moderate, and severe), whereas 131I-treated cats were divided into euthyroid and hypothyroid groups. Test sensitivity, specificity, and positive predictive value for identifying hyperthyroidism were higher for TSH-BAW (90.5%, 98.9%, and 86.9%) than TSH-CLIA (79.9%, 76.7%, and 21.7%; P < .001). Test sensitivity for identifying 131I-induced hypothyroidism was only 45.5% for T4 versus 100.0% for both TSH-CLIA and TSH-BAW (P = .03), whereas TSH-BAW had a higher positive predictive value (100%) than did either TSH-CLIA (81.2%) or T4 (71.9%). Serum TSH-BAW alone or together with T4 is a highly sensitive and specific diagnostic test for evaluating feline hyperthyroidism and iatrogenic hypothyroidism. Finding low serum TSH-BAW concentrations is most useful for diagnosing subclinical and mild hyperthyroidism, in which serum T4 remains within or only slightly above the reference interval.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis

Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. None.

How low can we (reliably) go? A method comparison of thyroid-stimulating hormone assays with a focus on low concentrations.

International guidelines concerning subclinical hyperthyroidism and thyroid cancer advice absolute cut-off values for aiding clinical decisions in the low range of thyroid-stimulating hormone (TSH) concentrations. As TSH assays are known to be poorly standardized in the normal to high range, we performed a TSH assay method comparison focusing on the low range. Sixty samples, selected to cover a wide range of TSH concentrations (<0.01 to 120 mIU/L) with oversampling in the lower range (<0.4 mIU/L), were used for the method comparison between three TSH immunoassays (Cobas, Alinity and Atellica). In addition, 20 samples were used to assess the coefficient of variation from duplicate measurements in these three methods. The TSH immunoassays showed standardization differences with a bias of 7-16% for the total range and 1-14% for the low range. This could lead to a different classification of 1.5% of all measured TSH concentrations <0.40 mIU/L measured in our laboratory over the last 6 months, regarding the clinically important cut-off value of TSH = 0.1 mIU/L. As the imprecision of the immunoassays varied from 1.6-5.5%, this could lead to a similar reclassification as the bias between immunoassays. We established the standardization differences of frequently used TSH assays for the total and low concentration ranges. Based on the proportional bias and the imprecision, this effect seems to have limited clinical consequences for the low TSH concentration range. Nevertheless, as guidelines mention absolute TSH values to guide clinical decision-making, caution must be applied when interpreting values close to these cut-offs.

Lower thyroid stimulating hormone concentrations linked to suicidal ideations among individuals with anxiety and mood disorders

IntroductionSuicidal behavior is quite common in individuals with anxiety and mood disorders (AMD). One of the coexistence factors in suicidal behavior is thyroid dysfunction, however the results are still controversial (Shen et al. J Affect Disord 2019;(1)180-185; Zhou et al., Transl Psychiatry. 2021;11(1):97). The role of thyroid function in suicidal ideation among individuals with comorbid AMD have not been thoroughly investigated.ObjectivesThe aim of this cross-sectional study was to identify potential associations between thyroid function and suicidal ideation in a sample of individuals with anxiety and mood disorders.MethodsThis exploratory study comprised 77 consecutive individuals with AMD (age range 18-73 years, 76% were females) attending the Psychiatry Day care unit. All individuals have been evaluated for current psychiatric diagnoses, suicidal ideation using the Mini International Neuropsychiatric Interview [M.I.N.I. 7.0.2]) as well as for socio-demographic factors and for current psychotropic medication use. Severity of depression and anxiety symptoms have been evaluated using the Patient Health Questionnaire-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). The biochemical blood tests were performed for the concentrations of thyroxine (FT4), triiodothyronine (FT3) and thyroid stimulating hormone (TSH). The univariate and multivariable logistic regression analyses were used to assess the association between biochemical parameters and suicidal ideation.ResultsOf all study individuals with AMD – 56% have been identified as having current SI. There were not significant differences according to age, gender, education, BMI, smoking, depression and anxiety symptoms and current psychotropics use between SI and non-SI individuals. Serum FT4, FT3 and TSH concentrations were within normal range. However individuals with SI had significantly lower TSH concentrations in comparison to the non-SI (1.54 (0.77) vs. 2.04 (1.22) IU/L, respectively; p = 0.049), without significantly differences in FT4 and FT3 concentrations. A multiple logistic regression, adjusting for sociodemographic factors and severity of mental symptoms revealed, that non-SI individuals with AMD were likely to have higher TSH levels than SI (odds ratio = 2.15 (95% CI 1.10–4.22; p = 0.027).ConclusionsAmong individuals with AMD, lower levels of TSH concentrations have been associated with presence of suicidal ideation, independently of sociodemographic factors and severity of depression and anxiety.Disclosure of InterestV. Liaugaudaitė Grant / Research support from: European Union (project No P-PD-22-150) under the agreement with the Research Council of Lithuania (LMTLT)., A. Podlipskytė: None Declared, J. Burkauskas Consultant of: Cronos, N. Mickuvienė: None Declared, V. Adomaitienė: None Declared, E. Zauka: None Declared, V. Steiblienė: None Declared

Anterior pituitary hormones in first-episode psychosis: a systematic review and meta-analysis

IntroductionAlthough the role of pituitary gland in schizophrenia and psychotic disorders has been studied for decades, evidence on anterior pituitary hormones in the early phases of psychoses – without the influence of chronicity, comorbidities, and pharmacological treatment – is mostly unclear and inconsistent.ObjectivesOur systematic review and meta-analysis was aimed at comparing the blood concentrations of adrenocorticotropic hormone (ACTH), follicle stimulating and luteinizing hormones (FSH and LH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) between people with drug-naïve first-episode psychosis (FEP) and healthy controls.MethodsWe searched main electronic databases for articles indexed up to September 2022. We appraised the quality of data. We carried out random-effects meta-analyses, generating pooled standardized mean differences (SMDs) and estimating between-study heterogeneity. Moreover, we performed sensitivity and meta-regression analyses.ResultsTwenty-six studies were included. People with drug-naïve FEP had higher ACTH (p&lt;0.001; moderate-to-high heterogeneity) and PRL (p&lt;0.001; high heterogeneity) concentrations, as well as lower TSH concentrations (p=0.001; low heterogeneity), than healthy subjects. Sensitivity analyses confirmed these findings. Data were not sufficient to perform meta-analyses on other hormones (FSH, LH, and GH).ConclusionsPeople with drug-naïve FEP have abnormal ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that anterior pituitary hormone secretion is altered in the first stages of schizophrenia and psychoses. Additional research is needed to clarify the complex interconnections between vulnerability, environmental factors, and pituitary hormones in FEP.Disclosure of InterestNone Declared

Cadmium toxicity could be a cause for thyroid problem

Every year World Thyroid Day is observed on May 25 to spread awareness on the disorders of thyroid gland and their prevention. Yet the increase in thyroid problems is unabated. In fact, thyroid is one of the most important endocrine glands that regulates all most all body functions of human beings. It synthesizes and secrets 2 main hormones, thyroxine(T4) and tri-iodothyronine(T3), both being regulated by thyroid-stimulating hormone (TSH). While the whole amount of circulating T4 is produced by the thyroid gland itself, T3 is mostly generated in liver and kidney by peripheral mono-deiodination of T4 with the help of an enzyme, 5'-deiodinase (5' D). Thyroid hormones are vital for the well-being of a person and their abnormal levels lead to health problems. People with thyroid abnormalities suffer either from hypo-functioning (hypothyroidism) or from hyper-functioning (hyperthyroidism) of the gland. However, most common thyroid problem is hypothyroidism and females suffer more from this as compared to males. According to Chiovato et al. (2019), hypothyroidism affects about 5% of the general population and 5% more are believed to be sufferers, but undiagnosed. Primary hypothyroidism is normally diagnosed with low serum thyroid hormones and high TSH concentrations than the normal reference ranges. Symptoms of hypothyroidism include intolerance to cold, mild to moderate weight gain, dry skin, puffiness of the body, peri-orbital swelling, chronic fatigue, constipation, depression, hoarse voice and menstrual irregularities.The consequences of untreated or under-treated hypothyroidism include cretinism, myxoedema and goitre, even coronary artery disease.

Serial measurement of thyroid hormones in hospitalised dogs with canine parvoviral enteritis: Incidence of non-thyroidal illness syndrome and its association with outcome and systemic inflammatory response syndrome

The aim of this study was to serially evaluate the serum concentrations of total thyroxine (tT4), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) in dogs with canine parvoviral enteritis (CPVE) during a 5-day hospitalisation period and assess the association of these hormone concentrations with the outcome and the development of systemic inflammatory response syndrome (SIRS). Dogs with confirmed CPVE that were hospitalised for at least 5 days were included. The thyroid hormones concentrations were measured on days 1, 3 and 5 of hospitalisation.Twenty-eight dogs were included. All (28/28, 100%), 19/28 (69.7%) and 23/28 (82.1%) dogs had a low serum tT4, fT4 and TSH concentration, respectively, on at least 1 day during the hospitalisation period. Overall, 11/28 (39.3%) dogs were diagnosed with SIRS on at least 1 day. In survivors, serum tT4 concentration was significantly higher on day 5 (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) compared to those on days 1 (<6.4 nmol/L, <6.4–20.1 nmol/L; P = 0.010) or 3 (7.6 nmol/L, <6.4−25.2 nmol/L; P = 0.019). Survivors had a significantly higher tT4 concentration (median, range: 11.8 nmol/L, <6.4–32.2 nmol/L) on day 5 compared to non-survivors (<6.4 nmol/L, <6.4–7.2 nmol/L; P = 0.002). Regardless of the day of hospitalisation, dogs with SIRS had significantly lower tT4 (<6.4 nmol/L, <6.4–16.3 nmol/L) compared to dogs without SIRS (8.6 nmol/L, <6.4–32.2 nmol/L; P = 0.006). A significant difference was also found in fT4 between dogs with SIRS (<3.9 pmol/L, <3.9–16.2 pmol/L) and dogs without SIRS (15.1 pmol/L, <3.9−59.2; pmol/L; P < 0.001). Non-thyroidal illness syndrome was frequently observed in dogs with CPVE, and a negative association between tT4 and fT4 concentrations and SIRS was noted. Serial measurements of tT4 concentrations appeared to have prognostic value.

Prognostic significance of low TSH concentration in patients with COVID-19 presenting with non-thyroidal illness syndrome

BackgroundLow free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI.MethodsPatients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality.ResultsOne hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42–5.552, P = 0.003).ConclusionsLow FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.

The effect of ketogenic diet on thyroid functions in children with drug-resistant epilepsy.

Ketogenic diet (KD) remains a valuable treatment option for children with drug-resistant epilepsy. However, it may cause many well-known adverse effects such as dyslipidemia or kidney stones. But, its effects on thyroid functions are largely unknown. The aim of this study was to investigate the effects of the KD on thyroid functions in children with drug-resistant epilepsy. A total of 66 children (35 females) aged 3-193 months (median, 52 months) with drug-resistant epilepsy who received a KD for at least 12 months were enrolled in the study. All children were started on KD with 3:1 ratio which was then adjusted as clinically necessary. Serum free-thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations were measured before starting treatment and at the first, sixth and twelfth months of treatment. Changes in FT4 and TSH concentrations over 12 months were analyzed. Median serum FT4 and TSH concentrations, and the frequencies of patients with low FT4 and high TSH concentrations did not change significantly in the study sample over the 12-month study period. Serum FT4 levels increased significantly and TSH concentrations decreased insignificantly in four patients receiving L-thyroxine replacement therapy. During the 12-month treatment period, BMI-SDS increased, and the number of antiepileptic drugs decreased significantly. It appears that KD therapy does not impair thyroid functions in children with drug-resistant epilepsy. KD can be used safely along with L-thyroxine replacement even in children with pre-existing subclinical hypothyroidism.

Acetylcholinesterase activity and thyroid hormone levels in Ecuadorian adolescents living in agricultural settings where organophosphate pesticides are used.

Organophosphates are frequently applied insecticides that inhibit acetylcholinesterase (AChE) activity resulting in cholinergic overstimulation. Limited evidence suggests that organophosphates may alter thyroid hormone levels, although studies have yielded inconsistent findings. We aimed to test the associations between AChE activity, a physiological marker of organophosphate exposure, and thyroid function in adolescents. We included information of 80 adolescent participants (ages 12-17y in 2016, 53% male) growing up in agricultural settings in Ecuador. We measured fingerstick erythrocytic AChE activity and hemoglobin concentration, and concurrent serum thyroid stimulating hormone (TSH) and free-T4 (fT4) concentrations. General linear models were used to test associations which adjusted for demographic and anthropometric variables. TSH associations were further adjusted for fT4. The mean (SD) AChE, TSH and fT4 levels were 3.77 U/mL (0.55), 2.82 μIU/ml (1.49) and 1.11ng/dl (0.13), respectively. Lower AChE activity, indicating greater organophosphate exposure, was marginally associated with greater fT4 concentrations (difference per SD decrease in AChE activity (β)=0.03ng/dL, [90% CI: 0.00, 0.06]) but not with TSH (β=-0.01 μIU/ml, [-0.38, 0.36]). Gender modified the AChE-TSH association (p=0.03). In girls, lower AChE activity was associated with higher fT4 levels (β=0.05ng/dL [0.01, 0.10]) and lower TSH concentrations (β=-0.51 μIU/ml, [-1.00, -0.023]). No associations were observed in boys. These cross-sectional findings suggest that alterations in the cholinergic system from organophosphate exposures can increase fT4 levels coupled with a beyond-compensatory downregulation of TSH in female adolescents. This is the first study to characterize these associations in adolescents.

Neonatal thyroid-stimulating hormone and association with attention-deficit/hyperactivity disorder.

Normal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid-stimulating hormone (TSH) 48-72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub-clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention-deficit/hyperactivity disorder (ADHD). To estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population-based birth cohort. Children with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD-10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003-2008) with available neonatal TSH concentrations below 10 mU/L (cut-off for potential congenital hypothyroidism) measured in dried blood spots sampled 48-72 hours after birth. In multivariable, quintile models the relationship appeared to follow a U-shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5-fold higher than children in the middle quintile (OR 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR 3.10, 95% CI 1.53, 6.30; boys OR 1.16, 95% CI 0.73, 1.84). ADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.

Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study

ObjectiveTo explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and...

Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study

Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05-1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29-0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96-2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08-2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. National Institute for Social Care and Health Research, Wales.

Thyrotoxic hypokalemic periodic paralysis

Hypokalemia is a serious and life-threatening clinical condition. We present a case of a 45-year-old male, with known hyperthyroidism presenting with profound tremor, irritability, quadriparesis, and labored breathing since morning, on the day of admission. Arterial blood gas analysis showed severe hypokalemia. Patient's vital was stabilized and patient's oxygen saturation was maintained on oxygen inhalation. Intravenous potassium chloride infusion was administered with regular monitoring of vitals and electrolytes. Patient's symptoms improved. Thyroid function testing showed high free T3 (tri-iodothyronine) and free T4 (thyroxine) with low thyroid-stimulating hormone concentration in the serum, indicating thyrotoxic hypokalemic periodic paralysis. Treatment with antithyroid drug carbimazole resulted in an improvement during the follow-up visit. Hypokalemia is believed to be a consequence of a massive shift due to increased sodium–potassium–adenosine triphosphatase (Na+K+ATPase) pump activity in the presence of elevated thyroid hormones.

The impact of thyroid hormones on patients with hepatocellular carcinoma.

Background & aimsHypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients.MethodsOf 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated.ResultsThyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9–15.7 months) vs. 7.3 months (5.4–9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5–13.6 months) vs. 3.3 months (2.2–4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3–3.3); p = 0.002) in multivariate analysis.ConclusionsTSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

Association between thyroid dysfunction and dysglycaemia: a prospective cohort study.

To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid-stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia. In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted. During a median 2.6 year follow-up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid-stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid-stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04-1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64-1.44). By contrast, participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia. People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify.

Serum vitamin B-12 in children presenting with vasovagal syncope.

The present study aims to determine the serum vitamin B-12 in children presenting with vasovagal syncope. This is a prospective review of 160 children presenting with vasovagal syncope. Subgroup analysis was done based on the results of head up tilt test. Head up tilt test gave positive results in 80 children and yielded negative results in the remaining 80 children. The tilt test positive children had significantly lower thyroid stimulating hormone concentrations (p=0.06), total iron binding capacity (p=0.04) and serum vitamin B-12 (p=0.01). The prevalence of vitamin B-12 deficiency was significantly higher in the tilt positive group (80% vs 52.5%, p=0.001). Out of 80 children with positive tilt test, 8 children (10%) showed cardioinhibitory response, 22 children (27.5%) demonstrated a vasodepressor response, 24 children (30%) displayed mixed response and 26 children (32.5%) had the postural orthostatic tachycardia syndrome. Erythrocyte sedimentation rate was significantly lower in the mixed response group than in the vasodepressor group (6.2±0.8 mm/h vs 14.3±2.5 mm/h, p=0.001). Serum vitamin B-12 was significantly lower in the postural orthostatic tachycardia syndrome (POTS) group than in the vasodepressor group (240.8±38.2 pg/mL vs 392.7±27.1 pg/mL, p=0.001). The prevalence of vitamin B-12 deficiency was significantly higher in the POTS group than in the vasodepressor group (92.3% vs 45.5%, p=0.001). Vitamin B-12 deficiency causes reduction in myelinization, deceleration in nerve conduction and elevation in serum concentrations of noradrenaline. These factors may contribute to the impairment of autonomic functions which are involved in the pathogenesis of vasovagal syncope.

Gender and Age Impact on the Association Between Thyroid-Stimulating Hormone and Serum Lipids.

The relationship between thyroid-stimulating hormone (TSH) and hyperlipidemia is still a topic of debate. We aimed to explore the impact of gender and age on the association between serum TSH and lipid profile in a large cohort of Chinese.This cross-sectional study enrolled 13,915 participants (8565 male, 5350 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and other serum parameters were collected. The associations between TSH and hyperlipidemia of males and females were analyzed separately after dividing TSH and age into subgroups. Odds ratio for hyperlipidemia was calculated by binary logistic regression models.Young males had significantly higher prevalence of hypercholesterolemia, hypertriglyceridemia, and high serum low-density lipoprotein-cholesterol than females, yet after menopause, females had higher prevalence than males. TSH was positively associated with hyperlipidemia independent of thyroid hormones. Males showed more reduced risks of hyperlipidemia in low TSH concentrations, while females demonstrated more enhanced risks of hyperlipidemia in high TSH concentrations. For instance, if TSH was lower than 0.3 μIU/mL, the risks of developing hypercholesterolemia and hypertriglyceridemia in males were only 0.198 (P < 0.01) and 0.425 (P < 0.05) of the reference TSH risks (between 2.0 and 3.0 μIU/mL), while in females the risks were 0.553 (P < 0.05) and 0.642 (P > 0.05), respectively. If TSH was higher than 4.0 μIU/mL, women displayed significantly higher risks of developing hypertriglyceridemia than the reference TSH risks (P < 0.05), yet, men did not demonstrate such significances.Our results showed thyroid hormone independent positive associations between serum TSH and lipids, which were substantially influenced by gender and age. Males demonstrated more protective effects of low TSH against hyperlipidemia, while females showed more detrimental effects of high TSH on hyperlipidemia.