Serum FT4 Levels Research Articles

Exploring Serum Anti-thyroid Peroxidase Antibodies and High-Sensitivity C-reactive Protein as Inflammatory Markers in Subclinical Hypothyroidism: A Comprehensive Study.

Background and aim Subclinical hypothyroidism (SCH) is a biochemical condition defined by elevated thyroid-stimulating hormone (TSH) levels with normal free thyroxine (FT4) levels, often occurring without overt clinical symptoms. Emerging evidence suggests a role for autoimmune and inflammatory processes, with anti-thyroid peroxidase antibodies (anti-TPO) and high-sensitivity C-reactive protein (hsCRP) as potential markers of thyroid autoimmunity and systemic inflammation. This study evaluates the significance of these markers in SCH to elucidate their association with disease progression and clinical symptoms. This study aims to assess the roles of anti-TPO and hsCRP as inflammatory markers in SCH and to examine their correlations with clinical symptoms, lipid profiles, and cardiovascular risk, to stratify patients based on their autoimmune and inflammatory profiles. Methodology A retrospective, cross-sectional study was conducted on 220 patients, including 170 diagnosed with SCH and 50 euthyroid controls. Patients were categorized into SCH with anti-TPO positivity (SCH+), SCH without anti-TPO positivity (SCH-), and euthyroid controls. Serum TSH, FT4, anti-TPO, and hsCRP levels were analyzed using chemiluminescent immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and turbidimetric immunoassay. Statistical analyses, including Kruskal-Wallis and correlation tests, evaluated associations between hsCRP, anti-TPO, and clinical parameters. Results SCH+ participants demonstrated significantly higher levels of TSH (7.6 ± 2.1 mIU/L), hsCRP (4.2 ± 1.6 mg/L), and anti-TPO antibodies (116.5 ± 34.8 IU/mL) compared to SCH- and controls (P < 0.001). hsCRP was elevated in 52.2% of SCH+ individuals, indicating a systemic inflammatory state, compared to 32.1% in SCH- and 16% in controls. Significant correlations were observed between hsCRP and TSH (r = 0.62, P < 0.001) and between hsCRP and anti-TPO (r = 0.58, P < 0.001) in SCH+ participants. SCH+ patients exhibited a higher prevalence of fatigue, cold intolerance, and lipid abnormalities, with total cholesterol and LDL levels markedly elevated compared to other groups. Conclusions Anti-TPO and hsCRP are valuable markers for identifying systemic inflammation and autoimmune activity in SCH, particularly in anti-TPO-positive individuals. Their integration into routine evaluation may help stratify SCH patients based on cardiovascular and metabolic risk, guiding early therapeutic interventions. Further, longitudinal studies are needed to explore their prognostic value and therapeutic implications.

Thyroid hormones in systemic lupus erythematosus: The catalyst for disease progression?

The study aimed to investigate the impact of varying thyroid function statuses on clinical and laboratory indicators in patients with systemic lupus erythematosus (SLE). A retrospective analysis was conducted on 258 patients with SLE, who were stratified according to thyroid function, renal involvement, and disease activity. The predictive value of thyroid hormones was evaluated using a receiver operating characteristic (ROC) curve. Among the 258 patients with SLE, 141 were classified as the normal group, while 117 exhibited thyroid hormone abnormalities, categorized into hypothyroidism (N=112) and hyperthyroidism (N=5) groups. Serum levels of FT3 and FT4 positively correlate with total protein and albumin, while negatively correlating with the SLE Disease Activity Index 2K (SLEDAI-2K) and 24-hour urinary protein (24hUP) (P<0.05). Compared to individuals without renal involvement, those with renal involvement exhibited lower levels of FT3 and FT4 (3.35±0.99 vs. 4.07±2.22, 12.92±3.14 vs. 14.63±3.39, P=0.001), along with elevated thyroid-stimulating hormone (TSH) levels (7.08±14.40 vs. 5.28±12.48, P=0.343). The subgroups in euthyroid (n=86) and hypothyroid (n=93) of SLE patients with renal involvement exhibited different characteristics (P<0.05). The levels of FT3 gradually decreased with increase of disease activity. The areas under the ROC curve of FT3, FT4, TSH and their combination were 0.651, 0.654, 0.643, 0.669, respectively (P<0.05). The correlation between thyroid function and the severity of SLE is significant, SLE patients with hypothyroidism exhibit more pronounced disease manifestations and an elevated risk of organ damage. SLE patients with low levels of FT3 and FT4 are prone to progressing to nephritis.

Effects of Metformin Therapy on Thyroid Volume and Functions in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Single-center Prospective Study.

Patients with impaired glucose metabolism have increased thyroid volume and a higher prevalence of nodules. Yet, some studies show that there is an improvement in these thyroid parameters after diabetes treatment. Our observational study aimed to reveal the effect of treatment on thyroid function, thyroid volume, and the presence of nodules in newly diagnosed type 2 diabetes mellitus (T2DM) patients who were started on metformin treatment. Euthyroid and subclinically hypothyroid patients with a serum TSH level of <10 mU/L, who were newly diagnosed with T2DM and started on metformin as an antidiabetic treatment and not used any thyroid medication previously, were included in our study. Patients' characteristics were recorded. Baseline and 6th-month serum thyroid function tests were scheduled. Baseline and 6th-month thyroid gland characteristics were examined by thyroid ultrasonography. A total of 101 (37 males, 64 females) newly diagnosed T2DM patients with euthyroid (n=95) or subclinical hypothyroidism (n=6) were included in the study. The mean age of the patients was 53.02 ± 11.9 years, and the mean BMI was 29.60 ± 3.9 kg/m2. Fifty-two (52%) patients were classified as obese. Body weight, BMI, serum TSH, ALT, Anti-TPO levels, and thyroid volume decreased significantly in the 6th-month compared to baseline values (p = 0.000; p = 0.000; p = 0.011; p = 0.022; p = 0.000, respectively). Serum anti-Tg, fT4, fT3 levels, and thyroid nodule count did not change significantly. A high agreement was found between the baseline and 6thmonth nodule counts (gamma= 0.886; p < 0.001) and the presence of multi-nodularity in the thyroid (gamma= 0.941; p < 0.001), but no significant change was observed. Anti-TPO levels showed a significant decrease in both with and without obesity groups at the end of 6 months (p = 0.003, p = 0.009, respectively). Serum TSH level decreased significantly only in non-obese subjects (p = 0.004), and thyroid volume decreased significantly only in obese subjects (p = 0.000). Our results suggest that metformin treatment significantly reduces body weight, BMI, thyroid volume, and serum TSH, ALT, and Anti-TPO levels in patients with newly diagnosed T2DM. Moreover, serum TSH levels showed a significant decrease in non-obese subjects, while thyroid volume showed a significant decrease in obese subjects.

Bailing capsule alleviates autoimmune thyroiditis regulating peroxisome proliferator-activated receptor signaling pathway: a multi-omics analysis.

To investigate the efficacy and potential mechanism of Bailing capsule (, BL) anti-autoimmune thyroiditis (AIT). Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), and inflammatory factors Interferon-gamma (IFN-γ), Interleukin-4, -10, and -12 (IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin (HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot (WB). BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acid-binding protein 4, acyl-CoA synthetase long-chain family member 1, and acyl-CoA dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT rats. BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferator-activated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.

A Study Correlating the Effects of Subclinical Hypothyroidism on the Known Modifiable Risk Factors of Coronary Artery Disease in Indian Adults.

Subclinical hypothyroidism (SCH) is synonymous with thyroid failure (a milder form). It is a condition characterized by normal laboratory ranges of serum FT4 and FT3 levels, but serum thyroid stimulating hormone (TSH) levels are slightly increased above the normal range. The leading aims and objectives of the study were: (1) establishing a correlation between the presence of modifiable risk factors of ischemic heart disease in subjects with SCH. (2) Quantification of the economic markers of ischemic heart disease in patients with SCH. This study was accomplished at the Department of Internal Medicine, Ramakrishna Mission Seva Pratishthan, Vivekananda Institute of Medical Sciences, Kolkata, for the duration of 1 year, from March 2020 to February 2021. The study variables included history, physical examination, clinical examination, and investigations. The individuals who met the inclusion criteria set for the study were included. All the participants were informed about the study, and their informed consent was obtained. Data were analyzed using Microsoft Excel spreadsheet, followed by Statistical Package for the Social Sciences (SPSS) (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism version 5. Of the total 80 subjects enrolled in the study, 54 were females and 26 were males. In the study sample, the mean age was 47.8 (+9) years. Different variables were analyzed, and the values obtained were recorded for statistical analysis. According to the study, there is a positive correlation between established coronary artery disease (CAD) risk factors, such as hypertension, abnormal lipid profiles, and elevated body mass index (BMI), and SCH. We also noted a strong correlation between SCH and elevated levels of uric acid, fasting blood sugar (FBS), postprandial glucose test (PPBS), and hemoglobin A1c (HbA1c). As a result, early detection and management of SCH may have cardiac preventive benefits.

Pyrethroid exposure biomarker 3-phenoxybenzoic acid (3-PBA) binds to transthyretin and is positively associated with free T3 in pregnant women

Pyrethroids constitute a large group of insecticides widely used in agriculture, indoor environments, and in vector control. Structurally, pyrethroids resemble thyroid hormones, and have been suggested to be thyroid hormone disruptors based on experimental studies. During pregnancy, even minor disturbances in maternal levels can affect fetal brain development. Therefore, we aimed to investigate whether three commonly used pyrethroids and their common metabolite, 3-PBA, were able to trigger thyroid disrupting effects on thyroid hormone production and transport, activation or deactivation of thyroid hormones, recycling of iodine, or on iodide uptake into the thyroid. Furthermore, we investigated associations between urinary 3-PBA concentrations (as biomarker of pyrethroid exposure) and serum concentrations of thyroid hormones in early pregnancy in the large prospective Odense Child Cohort (OCC).We found that the generic metabolite, 3-PBA, was capable of binding to transthyretin (TTR) at low concentrations, comparable to those reported in human cord blood. Among pregnant women in OCC, we found urinary 3-PBA concentrations to be positively associated with free triiodothyronine (fT3) serum levels. Displacement of thyroid hormones from TTR by pyrethroid exposure in early pregnancy may disturb the transplacental transport of thyroid hormones to the fetus during a very vulnerable window of development, including neural maturation. We did not find any evidence for thyroid disrupting effects in vitro for the three pyrethroids: Deltamethrin, α-cypermethrin, and etofenprox.

Thyroid hormone levels in patients with bipolar disorder: a systematic review and meta-analysis

PurposeTo investigate the difference in blood (serum/plasma) thyroid hormone (TH) levels, including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3), in bipolar disorder (BD) during different mood episodes (depression and mania) compared with healthy control (HC) and between manic episodes (BD-M) and depressive episodes (BD-D).MethodsAs of September 1, 2024, the electronic databases PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, and Clinical Trials. Gov were systematically searched with no language limitations. Standardized mean differences (SMD) with 95% confidence interval (CI) were summarized using a random effects model. The chi-squared-based Q test and the I2 test assessed the size of heterogeneity.ResultsThe 21 studies included a total of 3696 participants, Of the 2942 BD patients, 1583 were in depressive episodes 1359 were in manic episodes. The status of measuring blood TH levels included 2 studies in plasma and 19 in serum. Combined with the results of the sensitivity analyses, we obtained the following relatively reliable results: serum T3 (SMD: -0.63, 95%CI: -1.09 to -0.17) and FT3 (SMD: -0.42, 95%CI: -0.83 to -0.00) levels decreased significantly in BD-D compared to HC; serum T3 (SMD: -0.91, 95%CI: -1.49 to -0.32) levels decreased significantly and serum FT4 (SMD: 0.37, 95%CI: 0.14 to 0.60) levels increased significantly in BD-M than in HC; serum T3 (SMD: 0.87, 95%CI: 0.24 to 1.49) and FT3 (SMD: 0.27, 95%CI: 0.13 to 0.42) levels demonstrated a significant elevation in BD-M compared to BD-D. In the group of euthyroidism, apart from serum FT4 (SMD: 0.21, 95%CI: -0.15 to 0.58) levels showed no significant difference between BD-M and HC, other results above remained consistent.ConclusionSerum T3 and FT3 levels decreased significantly in BD-D compared to HC. Serum T3 levels decreased significantly and serum FT4 levels increased significantly in BD-M compared to HC. Serum T3 and FT3 levels increased significantly in BD-M than in BD-D. The temporality of changes in TH levels and BD progression demands further longitudinal studies to illustrate.Trial registrationNumber and date of registration for prospectively registered trials No. CRD42022378530.

Clinical efficacy of Chinese herbal medicine formula for Graves’ hyperthyroidism: A multicentre, randomized, double-blind, placebo-controlled clinical trial

Ethnopharmacological relevanceAccording to the theory of traditional Chinese medicine, Graves' disease (GD) is called ‘Ying Bing’, which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty ‘Waikezhengzong’, is a classic Chinese herbal formula for the treatment of ‘Ying Bing’ for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient. Aim of the studyTo obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial. Materials and methodsA multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves’ hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint. Results150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT3 levels (group A, p=0.0027; group B, p < 0.0001; group C, p=0.0028) and FT4 levels (group A, p < 0.0001; group B, p < 0.0001; group C, p < 0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p = 0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p < 0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p < 0.0001), eye (p=0.0490), tiredness (p < 0.0001), cognition (p < 0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety. ConclusionsPingkang granules significantly reduced serum FT3, FT4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism.

Thyroid hormones and prognosis in adults with status epilepticus: a retrospective study.

Thyroid hormone levels have been indicated to be associated with the functional outcome in critical illness. However, the studies on thyroid hormones and status epilepticus (SE) are rare. This study aimed to evaluate the predictive value of serum thyroid hormone levels on admission for unfavorable outcome in adult patients with SE. We investigated and validated the predictive value of serum thyroid hormone levels on admission for the prognosis of adult SE patients. We extracted the clinical information and outcomes of patients. Modified Rankin scale (mRS) scores were applied to assess the patients' functional outcome, and mortality at 30 days after SE onset was identified. Serum levels of thyroid hormones including free thyroxin (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) were detected on admission. We first analyzed the discovery cohort of 87 patients with SE. We found that 35.6% (31/87) of the patients had a poor outcome at discharge, and 18.4% (16/87) of the patients died during hospital stay and at 30-day follow up. The serum FT3 levels in the non-survivors group were significantly lower than those in the survivors group. Low T3 syndrome occurred in 29.9% (26/87) of SE cases and patients with low T3 syndrome were more likely to have unfavorable outcomes. Furthermore, we observed similar results in the external cohort, which validated our findings. Serum FT3 levels measured on admission are independently associated with 30-day mortality in SE patients. Additionally, low T3 syndrome may be a promising candidate for predicting SE prognosis.

Association between thyroid hormones and cognitive functioning in euthyroid elderly adults: a cross-sectional preliminary study from the NHANES 2011-2012 survey.

Changes in serum thyroid hormone levels may affect cognitive functioning in euthyroid individuals. This study used representative data from the National Health and Nutrition Examination Survey (NHANES) to comprehensively examine the association of thyroid hormones with different tests of cognitive functioning among US elderly people aged ≥60 years. This study was a cross-sectional preliminary study with a total of 734 participants from the NHANES 2011-2012 survey. Thyroid function was measured using competitive binding immune-enzymatic assays, while cognitive functioning was measured using a series of assessments, including the Consortium to Establish a Registry for Alzheimer's Disease-Word Learning (CERAD W-L), Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Weighted multiple linear regression models and binary logistic regression analyses were used to examine the association between thyroid hormone levels and cognitive functioning. All statistical analyses were performed using SPSS version 20.0, and R software. Weighted multivariable linear regression showed that FT3 was negatively associated with the Animal Fluency Test and DSST (β=-0.113, 95% CI: -3.279, -0.803, P=0.001; β=-0.062, 95% CI: -6.565, -0.470, P=0.024, respectively) after adjustment for potential covariates. subgroup analysis stratified by sex revealed a negative association between FT3 levels and the Animal Fluency Test in men (β=-0.163, 95% CI: -4.643, -1.153, P=0.001). For female participants, FT3 was negatively associated with not only the Animal Fluency Test but also DSST (β=-0.099, 95% CI: -3.543, -0.093, P=0.039; β=-0.093, 95% CI: -10.288, -1.326, P=0.011). Binary logistic regression showed that the significantly increased adjusted odds ratios (aORs) (95% CI) between the risk of impaired cognitive functioning and FT3 across Q3 and Q4 compared with Q1 were 2.025 (1.092, 3.753) and 2.365 (1.261, 4.433), respectively, for DSST in overall participants. Furthermore, there were significant differences between participants with and without impaired cognitive functioning for serum FT3 levels in overall participants based on DSST score (P=0.020). There was a significant inverse relationship between FT3 levels within the normal range and cognitive functioning after adjusting for potential covariates. Future longitudinal cohort studies should be conducted to determine the causal relationship between thyroid hormone levels and cognitive functioning.

5114 Establishment of Thyroid Storm Mouse Model and Therapeutic Effects of Ghrelin

Abstract Disclosure: C. Kurimoto: None. Y. Furukawa: None. T. Akamizu: None. A. Doi: None. K. Takeshima: None. S. Morita: None. H. Iwakura: None. H. Ariyasu: None. H. Furuta: None. M. Nishi: None. T. Matsuoka: None. Context: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, is caused by a combination of thyrotoxicosis and severe physical stresses. Infection is the most common triggering factor. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. Further, TS has limited therapeutic options. Objectives: We aimed to confirm the hypercytokinemia in patients with TS, establish a TS model mouse by triiodothyronine and lipopolysaccharide administration, and explore the therapeutic effects of ghrelin on TS. Methods: We evaluated serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. As a TS model, C57BL/6 mice were titrated with triiodothyronine and lipopolysaccharide to develop a lethal model with approximately 30% survival at 24 hours. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin on these parameters. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease without TS (55.7 ± 69.0 vs. 3.13 ± 1.41 pg/mL, P &amp;lt; .05, n=4 each). Next, we titrated the doses of T3 and LPS, aiming to achieve a survival rate of approximately 30% at 24 hours after administration. Two out of five mice in the T3 3.0 mg/kg group died, while none of the eight mice in the T3 1.0 mg/kg group died. Therefore, we determined that the appropriate T3 dose for the TS mouse model is 1.0 mg/kg, which is not lethal when administered alone. In the T3 1.0 mg/kg group (n=8), serum FT3 levels were approximately three times higher (15.3 ± 4.5 vs. 4.5 ± 0.7pg/ml) than those in the control group (n=8). Next, different doses of LPS was added to the T3 group. Survival at 24 hours post-dose was 60% in the T3 + LPS 0.2 mg/kg group (n=5) and 33% in the T3 + LPS 0.5 mg/kg group (n=5), while survival was 100% in the LPS 0.5 mg/kg alone group (n=5),. Based on these findings, the dosage for the murine TS model was determined to be “triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg”. This TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin at 300 µg/kg improved the survival rate to 66.7% (P &amp;lt; .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We confirmed the hypercytokinemia in patients with TS. Next, we established a lethal model simulating TS by inducing “thyrotoxicosis” by exogenous administration of thyroid hormones, and by inducing “sepsis” by intraperitoneal administration of LPS. The model mice exhibited similar pathophysiological status to human TS associated with induction of serum IL-6 and other biomarkers, which were improved by ghrelin. Presentation: 6/1/2024

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

6415 Resistance to Thyroid Hormone -A Challenge to Manage

Abstract Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None. Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T&amp;gt;C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism. Presentation: 6/3/2024

Pathological correlation between eosinophils and thyroid nodules based on medical image testing

Thyroid nodule is a common thyroid disease, but the study of its pathology and pathogenesis is still limited. As a non-invasive diagnostic method, medical image examination is of great value to study the pathological correlation of thyroid nodules. The purpose of this study was to investigate the expression of eosinophils in medical image examination and the pathological correlation between eosinophils and thyroid nodules. The study analyzed the pathological reports of a group of patients with thyroid nodules examined by medical images and performed corresponding imaging scans or examinations. The imaging data is processed, including image reconstruction, data transmission and other steps, to generate images that can be diagnosed by doctors. Thyroid function and parameters of leukocyte were collected and compared.The serum levels of TT4 and fT4 were observed lower in G2 group, while thyroid stimulating hormone (TSH) was higher compared to G1 group before surgery. Compared to G2 group, eosinophils count and percentage were lower in G1group (p < 0.05) post-surgery and lower ratio of eosinophils count with lymphocyte count (ELR) were observed in G1 group patients (p < 0.05).Elevated TSH is closely related to malignant TN per surgery, while lower ELR suggesting that TN removed thoroughly. Relevant cut-off values required further study to guide the diagnosis, treatment and follow-up of TN.

Associations between Thyroid Hormones and Cognitive Impairment in Patients with Parkinson's Disease.

This study aims to explore the correlation of serum thyroid hormone levels to cognitive impairments in Parkinson's disease (PD) patients. In this retrospective study, 106 Chinese patients without cognitive impairments and 94 patients with cognitive impairments, including 55 with mild cognitive impairment (PD-MCI) and 39 with PD dementia (PDD), were analyzed. Clinical data regarding the PD assessments, including disease duration, Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 scores, and Hoehn and Yahr (H-Y) staging, were analyzed. Cognitive functions were evaluated using the Montreal Cognitive Assessment score. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), were measured using ELISA. Significantly altered H-Y staging, disease duration, and UPDRS Part 3 scores were observed in PD patients with cognitive impairment compared with those without. Serum levels of FT3 were significantly decreased, while FT4 and TSH levels were significantly elevated in PD patients with cognitive impairment compared with those without. Combined detection of TSH, FT3, and FT4 showed value in distinguishing PD patients with and without cognitive impairment. Furthermore, a comparison of serum levels between PD-MCI and PDD patients revealed significant association between thyroid hormone levels and the degree of cognitive impairment in PD patients. Our findings suggest a relationship between changes in serum thyroid hormone levels and cognitive impairments in PD patients. Thyroid hormone levels, particularly FT3, may serve as potential markers for cognitive dysfunction in PD.

Association of Serum Uric Acid Level and Thyroid Function in Chronic Kidney Disease: A Hospital-Based Cross-Sectional Study From Northeast India.

Although the prevalence of thyroid dysfunction and hyperuricemia are independently high in patients with chronic kidney disease (CKD), there are limited data showing the association of serum uric acid and thyroid function in those with CKD. The aim of this study was to observe the alteration of both the serum uric acid level and thyroid function in CKD patients and to find the association between both. This observational cross-sectional study was conducted in a tertiary care hospital over a period of one year in Northeast India. A total of 50 CKD patients were enrolled. Their demographic profiles were studied. Serum urea, creatinine, thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), and free tetraiodothyronine (FT4) levels were measured to establish the correlation of serum uric acid along with each of the parameters separately. A p-value of <0.05 was considered statistically significant. In the CKD patients studied, serum uric acid exhibited positive correlations with serum creatinine (p = 0.001, r = 0.67), serum urea (p = 0.001, r = 0.69), and serum TSH levels (p = 0.001, r = 0.5). Conversely, serum uric acid showed negative correlations with serum TT4 (p = 0.001, r = -0.74), TT3 (p = 0.001, r = -0.6), FT4 (p = 0.001, r = -0.53), and FT3 (p = 0.001, r = -0.58) levels. There was a significant positive correlation between uric acid and TSH levels in CKD patients. Thus, early estimation of both parameters should be considered in CKD patients.

Gender Differences In Thyroid Cancer In A Tertiary Care Hospital Bangladesh

Background: The gender disparity in incidence, aggressiveness and prognosis is well established for thyroid cancer but the cause of the disparity is poorly understood. Objective: The main objective of the study was to evaluate the gender difference in thyroid disease. Materials and Methods: This cross sectional study was conducted in the Department of Otolaryngology-Head &amp; Neck Surgery of Bangabandhu Sheikh Mujib Medical University, Dhaka from January 2013 to December 2015. The thyroid gland was assessed by palpation in all patients. Estimation of serum TSH concentrations were performed by automated immune chemiluminescent assay. Results: In this study out of 400 thyroid cancer patients, 327 were females and 73 were males. The mean age was almost similar between male and female patients (p=0.245). HOMA-IR was significant higher in female patients than male patients (1.9±0.5 vs 1.7±0.6). FT3, FT4 and TPO antibody were significantly higher in male patients than female patients, whereas TSH level was significantly higher in female patients than male patients (5.7±2.9 vs 4.5±2.8 µIU/mL). In multivariate logistic regression analysis abnormal TSH patient had 3.61 (95% CI 1.66 to 7.81) times more likely to have female. Abnormal FT3 patient had 2.56 (95% CI 1.08 to 6.05) times more likely to have female. Abnormal TSH and FT3 were significantly associated with female patients. Conclusion: Serum TSH and FT3 levels were significantly associated with thyroid cancer especially for females. Our results suggest the necessity of monitoring TSH and FT3 in the population for thyroid cancer risk assessment, especially female.

Correlation of serum thyrotropin and thyroid hormone levels with diabetic kidney disease: a cross-sectional study

ObjectiveThe relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM).MethodsT2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves.ResultsThe prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium–glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61).ConclusionsIncreased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD.

Features of the functioning of the hypothalamic-pituitary-thyroid axis in mice with Lewis carcinoma on the background of induced hyperthyroidism

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory. The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT). Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum. Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted. Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

Titanium dioxide nanoparticles Disrupt ultrastructure and function of Rat thyroid tissue via oxidative stress

Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1β and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.