Overall, sex-and race/ethnicity-specific prevalence of thyroid dysfunction in US adolescents aged 12-18 years.

Background: Thyroid dysfunction significantly affects the health and development of adolescents. However, comprehensive studies on its prevalence and characteristics in US adolescents are lacking. Methods: We investigated the prevalence of thyroid dysfunction in US adolescents aged 12-18 years using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and 2007-2012 cycles. Thyroid dysfunction was assessed using serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) measurements. We analyzed the prevalence across demographic subgroups and identified associated risk factors. Results: The study included 2,182 participants, representing an estimated 12.97 million adolescents. The group had a weighted mean age of 15.1 ± 0.06 years, with males constituting 51.4%. Subclinical hyperthyroidism emerged as the most prevalent thyroid dysfunction, affecting 4.4% of the population. From 2001-2002 to 2011-2012, subclinical hyperthyroidism remained consistent at 4.99% vs. 5.13% in the overall cohort. Subclinical and overt hypothyroidism was found in 0.41 and 1.03% of adolescents respectively, and overt hyperthyroidism was rare (0.04%). The prevalence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in the overall population were 5.8 and 9.8%, respectively. Positivity for TgAb was risk factors for hypothyroidism, while older age, female and Black Americans were risk factors for hyperthyroidism. Female adolescents and adolescents with an older age were more likely to be positive for TPOAb and TgAb, while Black and Mexican Americans had a lower risk of TPOAb and TgAb positivity. Conclusion: Subclinical hyperthyroidism was the most common form of thyroid dysfunction, and its prevalence remained stable from 2001-2002 to 2011-2012. Notable disparities in the prevalence of hyperthyroidism and antibody positivity were observed among different age, sex and racial/ethnic groups.

Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Vitamin D and thyroid function: A mendelian randomization study.

BACKGROUND: Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function. METHODS: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis. RESULTS: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02). CONCLUSIONS: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.

Reduced serum CLCF1 levels in hyperthyroidism patients and T3-treated mice.

Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue.

Minor hyperthyroidism with normal levels of thyroid-stimulating hormone receptor antibodies: a case report.

The present report describes for the first time a case of diffuse hyperthyroidism in a 30-year-old female patient who had normal levels of thyroid-stimulating hormone receptor antibodies (TSHR-Ab), slightly elevated plasma levels of thyroid hormones, and slightly increased thyroid blood flow. Seven years before, after severe stress, she had Graves' disease with elevated plasma levels of TSHR-Ab. The patient's recent medical history included mental stress and autonomic dysfunction. This report describes a mild form of hyperthyroidism in terms of elevated plasma levels of thyroid hormones and Doppler ultrasonography data; this condition was first defined as 'minor hyperthyroidism'. The examination data suggest a probable secondary role of the immune system and primary role of the autonomic nervous system in the pathogenesis of Graves' disease.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

A systematic review of subclinical hyperthyroidism guidelines: a remarkable range of recommendations.

Background: Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations. Methods: Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Results: Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months. Conclusion: This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There isa need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Assessment of hemostasis in hyperthyroid and euthyroid cats using two viscoelastic assays and platelet aggregometry.

BACKGROUND: Hyperthyroidism in humans is associated with a hypercoagulable state and an increased risk of thromboembolism. OBJECTIVE: To evaluate hemostatic variables in hyperthyroid and euthyroid cats with the hypothesis that hyperthyroid cats will have evidence of altered hemostasis consistent with a potential hypercoagulable state. ANIMALS: Client-owned hyperthyroid (n = 16) and euthyroid (n = 15) cats over 8 years of age. METHODS: Prospective observational study. Hyperthyroid and euthyroid cats were enrolled. Rotational thromboelastometry (ROTEM), whole-blood platelet impedance aggregometry (WBPIA) and a point-of-care viscoelastic coagulation monitor (VCM-Vet) were performed immediately after minimally traumatic venipuncture under sedation. RESULTS: Hyperthyroid cats had significantly higher values for variables as assessed by VCM-Vet: A10 (34 [17-47] vs 25 [17-38], P = .003); A20 (39.5 [23-55] vs 31 [21-45], P = .003); and MCF (41 [24-58] vs 35 [22-49], P = .03). Hyperthyroid cats had significantly different values versus the euthyroid cohort as assessed by different ROTEM channels: increased A10, INTEM (61.5 [39-75] vs 54 [23-66], P = .007) and FIBTEM (18 [10-35] vs 13 [2-27], P = .01); increased A20, INTEM (68 [45-78] vs 61 [30-70], P = .006) and FIBTEM (17 [10-34] vs 11 [2-25], P = .002); increased MCF, EXTEM (72 [65-81] vs 69 [34-78], P = .04), INTEM (70 [45-85] vs 62 [35-71], P = .01) and FIBTEM (18 [13-37] vs 14 [3-27], P = .02); increased alpha angle, EXTEM (80 [68-85] vs 76 [41-84], P = .01); shortened CT, EXTEM (52.5 [29-73] vs 60 [52-92], P = .003) and FIBTEM (52.5 [16-75] vs 65 [53-165], P = .001); and decreased ML, FIBTEM (20 [1-36] vs 33 [19-59], P <.001). No significant differences were found with WBPIA. CONCLUSIONS AND CLINICAL IMPORTANCE: The hyperthyroid cats in this study had evidence of altered hemostasis as assessed by 2 viscoelastic methodologies, and characterized by increased clot amplitude, firmness, and faster coagulation times vs euthyroid controls.

The impact of thyroid function on total spine bone mineral density in postmenopausal women.

PURPOSE: Osteoporosis has been a widespread concern for older women, especially postmenopausal women. Thyroid function is crucial for bone metabolism. However, the relationship between thyroid function variation within thyroxine reference range and bone mineral density (BMD) remains ambiguous. The objective of this study was to evaluate the effect of subclinical hypothyroidism or hyperthyroidism on total spinal BMD in postmenopausal women. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010, multivariable weighted logistic regression was used to evaluate the relationships between total spine BMD and TSH among postmenopausal women aged ≥50. RESULTS: After accounting for a number of variables, this study discovered that the middle TSH tertile was associated with a decreased probability of osteoporosis. Additionally, the subgroup analysis revealed that postmenopausal women over the age of 65 or people with an overweight BMI had a clearer relationship between total spine BMD and TSH. CONCLUSION: The total spinal BMD had a positive relationship with thyroid stimulating hormone in postmenopausal women, and that appropriate TSH level (1.38-2.32 mIU/L) was accompanied by higher total spinal BMD.

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

OBJECTIVE: 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. ANIMALS: 169 untreated hyperthyroid cats, 53 cats treated with radioiodine (131I), 12 cats with chronic kidney disease (CKD), and 78 clinically healthy cats. METHODS: 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. RESULTS: 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%). CLINICAL RELEVANCE: 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.

Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Study on the Relationship Between Serum Iodine and Thyroid Dysfunctions: a Cross-Sectional Study.

The relationship between serum iodine (SIC) and thyroid dysfunctions in adults is poorly understood, and this study aimed to explore their relationship. A total of 1320 participants were included in the final analysis. We collected basic demographic information, blood, and spot urine samples to determine serological indices and iodine nutritional status. The median (IQR) of urinary iodine (UIC)/urinary creatinine (UCr), UIC, SIC were 138.1 (91.1, 207.6) µg/g, 155.8 (94.5, 211.1) µg/L, and 70.6 (59.8, 83.9) µg/L, respectively. The 90% reference ranges for UIC/UCr and SIC were 66.5-349.8 mg/g and 49.3-97.1 µg/L. SIC was positively correlated with UIC and UIC/UCr. The prevalence of overt hypothyroidism and subclinical hypothyroidism in female was significantly higher than that in male (P = 0.02, P = 0.002). In male, subjects above the upper reference value of SIC (97.1 µg/L) had a higher risk of subclinical hyperthyroidism (OR = 4.46, 95% CI: 1.29, 12.8) and overt hypothyroidism (OR = 5.59, 95% CI: 1.88, 6.42). In female, subjects below the lower reference value of SIC (49.3 µg/L) had a higher risk of overt hypothyroidism (OR = 2.18, 95% CI: 1.10, 4.06), TgAb positive (OR = 1.97, 95% CI: 1.15, 3.32) and TPOAb positive (OR = 2.48, 95% CI: 1.41, 4.26). In conclusion, serum iodine can be used as an indicator to evaluate iodine nutritional status and thyroid dysfunctions. Higher serum iodine concentration was associated with an increased risk of subclinical hyperthyroidism and overt hypothyroidism in men; lower serum iodine concentration was associated with an increased risk of overt hypothyroidism and positive TgAb and TPOAb in women.

Postoperative thyroid crisis in an 11-year old male with McCune-Albright syndrome and atypical triiodothyronine hyperthyroidism: A case report.

RATIONALE: McCune-Albright syndrome (MAS) is a rare heterogeneous clinical disease caused by sporadic, somatic, and postzygotic mutations. Thyroid crisis is even rare in patients with MAS, and we report the clinical outcomes of the first case of a MAS patient with atypical triiodothyronine (T3) hyperthyroidism who developed thyroid crisis after orthopedic surgery. PATIENT CONCERNS: The patient with MAS and atypical T3 hyperthyroidism was an 11-year-old man who had undergone surgery for a right femur fracture and shepherd bending deformity. His main symptoms were dizziness, nausea, and vomiting with elevated body temperature because of developed thyroid crisis. Thyroid function tests showed high T3 and remarkably high free T3 levels, and remarkably increased thyrotropin level, but unchanged thyroxine and free thyroxine levels. DIAGNOSIS: The patient was diagnosed with postoperative thyroid crisis following surgery for a right femur fracture, shepherd bending deformity, and MAS with atypical T3 hyperthyroidism. INTERVENTIONS: Propranolol was intravenously administered. The therapy included intravenous hydrocortisone, a saturated solution of potassium iodine and propylthiouracil, and continuous physical cooling. OUTCOMES: The patient was discharged after achieving a stable condition with normal thyroid and liver function after surgery because of active anti-thyroid crisis treatment. LESSONS: The operation of such patients should focus on the pre-operative heart rate, platelet level, and thyroid hormone levels. Abnormal values should be adjusted to the normal range, and such patients should achieve complete hemostasis and transfuse with blood following surgery anemia.

Analytical validation of the LiCA® high-sensitivity human thyroid stimulating hormone assay.

BACKGROUND: We aimed to assess the analytical characteristics of a new high-sensitivity human thyroid stimulating hormone (hTSH) assay on a light-initiated chemiluminescent immunoassay system (LiCA Smart) and examine the utility of this assay in the context of profoundly low TSH levels (<0.01 mIU/L). METHODS: Analytical validations included precision, linearity, reportable range, analytical sensitivity, interference, reagent lot-to-lot and between-instrument variability, and method comparisons. Additionally, a cross-sectional study was performed to evaluate the assay for the detection of profoundly low TSH levels in comparison to those of two other ultrasensitive hTSH assays. RESULTS: Within-run and within-lab imprecisions (%CV) were < 5% at all concentrations studied. A satisfactory linearity (R = 0.998, change in recovery < 5%) was verified over the entire measuring range. Method comparisons demonstrated a reasonable agreement (R > 0.99, median bias < 5%) between LiCA and Cobas, ADVIA, UniCel or Architect. The limit of quantitation was 0.0019 mIU/L. Comparative measurements of 236 patient samples with profoundly low TSH levels (<0.01 mIU/L) by LiCA, Cobas, and Architect revealed that the detection rate observed with LiCA (67.8%) was significantly higher than that with Cobas (28.0%) or Architect (21.7%). In a further comparative follow-up of patients with overt hyperthyroidism who were receiving treatment, an earlier recovery response of TSH was observed in LiCA. CONCLUSIONS: The LiCA Smart hTSH is a precise and highly sensitive fourth-generation assay. The assay demonstrated superior detection sensitivity for profoundly low TSH levels and was acceptable for clinical use.

Association of Maternal Thyroid Function with Gestational Hypercholanemia.

Background: High bile acid concentration is associated with adverse perinatal outcomes (i.e., stillbirth and preterm birth) and experimental studies indicate that thyroid hormone regulates bile acid metabolism, but this has not yet been translated to clinical data in pregnant women. We aim to explore the association of thyroid function with bile acid concentrations and the risk of gestational hypercholanemia. Methods: This study comprised 68,016 singleton pregnancies without known thyroid or hepatobiliary diseases before pregnancy and thyroid medication based on a prospective cohort. Thyroid function and serum total bile acid (TBA) were routinely screened in both early (9-13 weeks) and late pregnancy (32-36 weeks). Hypercholanemia was defined as serum TBA concentration ≥10 µmol/L. Multiple linear regression models and multiple logistic regression models were performed. Results: A higher free thyroxine (fT4) during both early or late pregnancy was associated with a higher TBA concentration and a higher risk of hypercholanemia (all p < 0.01). A higher thyrotropin (TSH) in early pregnancy was associated with a higher TBA concentration in early pregnancy (p = 0.0155), but with a lower TBA concentration during later pregnancy (p < 0.0001), and there was no association of TSH with hypercholanemia. Overt hyperthyroidism in late pregnancy was associated with a 2.12-fold higher risk of hypercholanemia ([confidence interval; CI 1.12-4.03], p = 0.021) and subclinical hyperthyroidism during later pregnancy was associated with a 1.5-fold higher risk of hypercholanemia ([CI 1.14-1.97], p = 0.0034). Sensitivity analyses indicated that a high fT4 throughout pregnancy was associated with a higher risk of hypercholanemia rather than only in early or late pregnancy. Conclusions: A higher fT4 concentration during either early or late pregnancy, but not the TSH concentration, is associated with higher TBA and a higher risk of gestational hypercholanemia. Furthermore, hyperthyroidism during pregnancy could be a novel risk factor for hypercholanemia.

Relationship between Menopause and Complications of Hyperthyroidism in Female Patients in Iraq.

Hyperthyroidism is a health problem characterized by an overactive thyroid gland, resulting in extra triiodothyronine (T3) and thyroxine (T4) production, as well as a decrease in thyroid-stimulating hormone (TSH). The oxidative stress indicators in hyperthyroid patients and the relationship with impaired metabolism of lipid are still controversial, especially in menopausal women suffering from a lack of ovulation hormones. In this study, blood samples were withdrawn from 120 subjects, including healthy premenopausal (n=30) and postmenopausal women (n=30) as control groups (G1 and G2), as well as 30 hyperthyroid women in each group of premenopausal and postmenopausal patient groups (G3 and G4). The levels of T3, T4, and TSH, blood pressure, and lipid profiles, such as triglyceride, total cholesterol (TC), high-density lipoprotein, and low-density lipoprotein, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and advanced oxidation protein products (AOPP) in the two healthy control groups and patient groups with hyperthyroidism were measured. In addition, serum progesterone levels were measured by the Bio-Merieux kit France, according to the manufacturer's instructions. The results revealed a significant decrease in SOD activity in the postmenopausal group, as compared to that in premenopausal women and control groups. Hyperthyroidism groups demonstrated a significant increase in MDA and AOPP levels, compared to control groups. Patient groups reported a decreased level of progesterone, in comparison with control groups. Moreover, there was a significant increase in T3 and T4 in patient groups (G3 and G4), compared to that in control groups (G1 and G2). There was a significant increase in systolic and diastolic blood pressure in menopausal hyperthyroidism (G4), compared to that in other groups. The TC decreased significantly in G3 and G4, compared to that in both control groups (P<0.05); nonetheless, there was no significant difference between patient groups (G3 and G4), as well as between control groups (G1 and G2). The study suggested that hyperthyroidism causes an increase in oxidative stress, which negatively affects the antioxidant system and drops levels of progesterone in both premenopausal and postmenopausal female patients. Therefore, low levels of progesterone are linked with hyperthyroidism, leading to aggravating symptoms of the disease.

Resting Energy Expenditure and Cold-induced Thermogenesis in Patients With Overt Hyperthyroidism.

CONTEXT: Thyroid hormone (TH) is crucial for the adaptation to cold. OBJECTIVE: To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. METHODS: This was a prospective cohort study at the endocrine outpatient clinic of a tertiary referral center. Eighteen patients with overt hyperthyroidism were included. We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In 14 of the 18 patients, energy expenditure (EE) was measured before and after a mild cold exposure of 2 hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at 8 positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. RESULTS: Free thyroxine (fT4) and free triiodothyronine (fT3) decreased significantly over time (fT4, P = .0003; fT3, P = .0001). REE corrected for lean body mass (LBM) decreased from 42 ±â€…6.7 kcal/24 hour/kg LBM in the hyperthyroid to 33 ±â€…4.4 kcal/24 hour/kg LBM (-21%, P < .0001 vs hyperthyroid) in the euthyroid state and 3 months later to 33 ±â€…5.2 kcal/24 hour/kg LBM (-21%, P = .0022 vs hyperthyroid, overall P < .0001). fT4 (P = .0001) and fT3 (P < 0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (P = .96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. CONCLUSION: CIT is not increased in patients with overt hyperthyroidism.

Association Between Serum Cystatin C and Thyroid Diseases: A Systematic Review and Meta-Analysis.

Background: Cystatin C (CysC) is often used to diagnose and monitor renal diseases. Although some studies have investigated the association between serum CysC levels and thyroid diseases, their reported results were inconsistent. Therefore, the relationship between CysC levels and thyroid diseases remains controversial. Aim: This meta-analysis aimed to statistically evaluate serum CysC levels in patients with thyroid diseases. Methods: A literature search was conducted using the PubMed, Web of Science, Embase, EBSCO, and Wiley Online Library databases. The following search terms were used for the title or abstract: "Cystatin C" or "CysC" in combination with the terms "thyroid disease", "thyroid function", "hypothyroidism", or "hyperthyroidism". The results of the systematic analysis were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Results: Eleven articles (1,265 cases and 894 controls) were included in the meta-analysis. The results of the meta-analysis showed that the serum CysC levels of patients with hyperthyroidism were significantly higher than those of the controls (SMD: 1.79, 95% CI [1.34, 2.25]), and the serum CysC levels of patients with hypothyroidism were significantly lower than those of the controls (SMD -0.59, 95% CI [-0.82, -0.36]). Moreover, the treatment of thyroid diseases significantly affected serum CysC levels. Conclusions: To the best of our knowledge, this meta-analysis is the first to evaluate serum CysC levels in patients with thyroid diseases. Our findings suggest that thyroid function affects serum CysC levels and that serum CysC may be an effective marker for monitoring thyroid diseases. Systematic Review Registration: PROSPERO [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258022], identifier CRD42021258022].

Expression of Circulating Rennin-Angiotensin-Aldosterone-Related microRNAs in Patients with Thyrotoxic Heart Disease.

Thyrotoxic heart disease (THD) is a common and severe complication of hyperthyroidism and the etiology of this complication remains poorly understood. Activation of the rennin-angiotensin- aldosterone system by excess thyroxin is one of the major factors that contribute to the pathogenesis of THD. Several microRNAs such as miR-21, miR-155, miR-208a, and miR-499 are closely related to the rennin-angiotensin-aldosterone system and therefore should be involved in this process. Our study intends to explore whether these miRNAs are involved in the pathogenesis of THD, and if these miRNAs could be secreted into the circulation and serve as sentinel indicators for THD. Though there is a trend of elevation of miR- 155 in THD than in simple hyperthyroidism patients, we did not find statistically significant differences in the expression of these miRNAs in the blood of THD patients, but we found that miR-155 was significantly up-regulated in patients with Graves' disease with or without THD in comparison with healthy controls. Thus, miR-155 can serve as a novel biomarker for Graves' disease and can play important roles in pathogenesis of Graves' disease.