TSH Levels Research Articles

Predictors for thyroid dysfunction after discontinuation of levothyroxine in children and adolescents with Hashimoto thyroiditis

Purpose: Few data on the clinical course after levothyroxine (L-T4) discontinuation in pediatric patients with Hashimoto thyroiditis (HT) are available. We investigated outcomes and predictors for successful withdrawal from L-T4 among children with HT.Methods: Among 168 patients diagnosed with HT between January 2000 and March 2021 at Seoul National University Children’s Hospital and in whom L-T4 therapy was initiated during childhood, we attempted to discontinue this therapy in 47, 3 boys and 44 girls. L-T4 was restarted when patients developed overt or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels≥10 mIU/L) after L-T4 discontinuation.Results: Median age at discontinuation was 15.4 years (12.7–18.4 years) with a median duration of L-T4 therapy of 47 months (20.3–80.3 months). During the median 30 months of follow-up (10.6–61.0 months) after L-T4 discontinuation, 33 (70.2%) developed thyroid dysfunction. Among these patients, 17 were eventually restarted on L-T4. TSH levels over 50 mIU/L at L-T4 initiation (hazard ratio, HR 3.5, P=0.002), age under 12 years at L-T4 discontinuation (HR 11.1, P=0.0001), and TSH levels higher than the upper 50% of normal (above 2.25 mIU/L in the present study) at L-T4 discontinuation (HR 2.7, P=0.014) were significantly predictive for overt hypothyroidism or subclinical hypothyroidism after L-T4 discontinuation. In addition, age under 12 years at L-T4 discontinuation was only predictive factor for restarting L-T4 medication (HR 4.3, P=0.012).Conclusion: L-T4 discontinuation in pediatric patients with HT resulted in thyroid dysfunction in 70.2% of cases; 36.2% of patients who attempted discontinuation required resumption of L-T4. Older age and lower TSH levels at L-T4 discontinuation were advantageous for successful withdrawal.

A longitudinal observational study on activated partial thromboplastin time in hypothyroidism and effect of thyroxine supplementation

Background: Hypothyroidism is a common condition characterized by thyroid hormone deficiency, which, if untreated, can lead to severe health consequences and even death. Due to the wide range of clinical presentations and non-specific symptoms, hypothyroidism is primarily diagnosed biochemically. It can result from congenital thyroid abnormalities or iodine deficiency. Aims and objectives: Aim: To evaluate the correlation between hypothyroidism and Activated Partial Thromboplastin Time (aPTT) and assess the effect of thyroxine supplementation. Objective: To study the impact of levothyroxine supplementation on aPTT in hypothyroid patients. Materials and methods: This observational study was conducted at the General Medicine outpatient clinic and inpatient wards at Al-Ameen Medical College and Hospital, Vijayapura, from September 2022 to March 2024. A total of 80 hypothyroid patients of both sexes were included. TSH, Free T4, and aPTT levels were measured with appropriate aseptic precautions. Results: The majority of subjects were females (90%), with the highest proportion (31.3%) aged 26-35 years. The mean ± SD of pre-thyroxine TSH was 25.453 ± 19.9073, which significantly decreased to 4.299 ± 0.6738 post-thyroxine. aPTT values also decreased significantly post-treatment. A positive correlation was found between TSH and aPTT, while aPTT had a negative correlation with T3 and T4 levels. Conclusion: aPTT is significantly elevated in hypothyroid patients and shows a positive correlation with TSH levels. Regular monitoring of aPTT should be included in the follow-up of hypothyroid patients.

Relationship between thyroid function and lipid atherogenic profile in pediatric patients with multisystem inflammatory syndrome associated with COVID-19

IntroductionConcurrent alterations in the metabolic profile and thyroid dysfunction, including non-thyroidal illness syndrome (NTIS) has been reported in multisystem inflammatory syndrome in children (MIS-C). Considering the influence of thyroid hormones (TH) on lipid metabolism, we explored the relationship between thyroid function and the atherogenic lipid profile in children with MIS-C at admission and during a 12-month follow-up.Patients and methodswe considered children admitted for MIS-C. Total and HDL cholesterol, triglycerides (TG), fasting plasma glucose, fasting plasma insulin as well as free T3 (FT3), free T4 (FT4), and TSH were assessed at diagnosis within 24 h of admission and during follow-up. TG/HDL ratio, no-HDL/HDL ratio and atherogenic index of plasma was also considered as atherogenic risk markers.Resultswe monitored 56 children. On admission, pathological levels of FT3, FT4, TSH, TG, TC, HDL, TG/HDL ratio, no-HDL/HDL ratio, and AIP were detected. Correlation analyses revealed associations between FT3, FT4, and lipid markers and TSH with TG. During monitoring, while complete restoration of TH balance was achieved at 12 months, some patients still exhibited an altered lipid profile, without correlation between thyroid function and lipid markers.Conclusionswe supported a relationship between thyroid function and an atherogenic lipid profile in children with MIS-C. This may result from interactions between adaptive and innate metabolic responses and genetic predisposition. Elucidating the relationship between TH and metabolic pathways during infections could help identify new biomarkers to prevent acute and fatal outcomes, improving patient prognosis and protecting long-term health.

A Real-Life Study in Patients Newly Diagnosed with Autoimmune Hashimoto’s Thyroiditis: Analysis of Asthenia as Admission Complaint

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.

Subclinical hypothyroidism and plasma levels of commonly prescribed anti-seizure medications

Background: Epilepsy remains the most common neurological problem worldwide. Most commonly prescribed antiseizure medications (ASMs) like phenytoin, sodium valproate, and carbamazepine show high inter-individual variability in bioavailability due to genetic and epigenetic factors resulting in either therapeutic failure or toxicity. In our study, we aim to determine the association between subclinical hypothyroidism and the plasma levels of these commonly prescribed ASMs, leading to either therapeutic failure or adverse drug reactions. Methods: We collected demographic data, details about the antiepileptic medication, and plasma levels of ASMs (phenytoin, carbamazepine, and sodium valproate) from patients on antiseizure medications who came for routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) estimated plasma levels of the antiseizure medications as per the TDM laboratory standard operating procedure (SOP) and thyroid function test (TSH) by a standard enzyme-linked immune-sorbent assay (ELISA) kit. Results: Of the 158 patients who had TDM, 75.31% were taking sodium valproate, 15.18% were on phenytoin, and 9.49% were on carbamazepine monotherapy. In our study, we found that 12 patients (7.59%) had TSH levels between 4 to 10 mIU/l, indicating subclinical hypothyroidism (SCH). The plasma drug levels of all 12 patients who had SCH were found to be below the therapeutic range. Conclusions: This study has established a significant association between ASMs, particularly sodium valproate, and thyroid dysfunction, specifically SCH, in patients with epilepsy. Our findings suggest that prolonged ASM therapy can lead to thyroid disturbances, warranting careful monitoring of thyroid function in these patients.

Hypothyroidism Induced by a TSH Receptor Peptide-Implications for Thyroid Autoimmunity.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro. During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered invivo. Methods: In order to examine the effect of invivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

A-9-Years-Old Female with Diabetes Mellitus Type 1 with Hyperthyroidism

Diabetes Mellitus Type 1 (DMT1) and thyroid disease can occur together, which is defined as a variant of autoimmune polyglandular syndrome type 3. It is known that the action of insulin and thyroid hormones affect cellular metabolism, thyroid hormones contribute to carbohydrate metabolism and pancreatic function. Since the thyroid gland plays a central role in the regulation of metabolism, abnormal thyroid function can have a major impact on the control of diabetes and poor glycemic control can cause alterations in thyroid hormone. A female, 9 years old, with decreased consciousness. Previous medical history, polyuria, increased appetite, and drastic weight loss. She also complained of sweating even in a cold room and was often emotional. On physical examination, there was fever, shortness of breath, tachycardia, and a soft and diffused slightly enlarged thyroid gland, with no bruit on auscultation. Laboratory tests showed blood glucose levels at 739 mg/dL, HbA1c 9.2%, C-peptide 0.2 ng/mL, TSH levels 0.01 µIU/mL, FT4 levels 2.77 ng/dL, the presence of metabolic acidosis, proteinuria, glucosuria, and ketonuria. Thyroid dysfunction will have a negative effect on DM control while poor glucose control will harm the work of thyroid hormones. Improvement in glycemic control and routine insulin injection with the right dose will reduce the risk of diabetic vascular and metabolic complications onset and progression.

Characterizing cognitive phenotypes and clinical correlates in type 2 diabetes using fuzzy clustering and decision tree analysis

Cognitive impairment is frequently seen in patients with type 2 diabetes (T2DM), ranging from mild impairment to dementia. However, our knowledge of the specific profiles and risk factors for these different levels of impairment is limited. In this study involving 152 patients with T2DM, cognitive function was assessed using the Montreal Cognitive Assessment test. The Fuzzy C-means clustering algorithm was utilized to group individuals with similar cognitive characteristics. The study evaluated how well clinical parameters could classify characteristics of clusters using the Classification and Regression Trees algorithm. ROC analysis was then used to assess the classification success. Three distinct cognitive clusters were identified. Cluster 1 had the poorest cognitive performance and was characterized by more women, lower education levels, and lower levels of iron, hemoglobin, and creatine. Cluster 3, the amnestic cluster, was distinguished by low TSH levels. The decision tree model highlighted several parameters, including education level, hemoglobin, duration of diabetes mellitus (DM), iron, TSH, gender, family history of diabetes, and microalbumin/creatinine ratio, as significantly affecting the distinction of cognitive clusters. Diabetes-associated cognitive impairment stems from multifaceted pathophysiological mechanisms influenced by complex risk factors, resulting in diverse types of cognitive deficits.

Reproductive life and differentiated thyroid carcinoma in women: reciprocal influences on their respective outcome.

To analyze the reciprocal influences between female reproductive life and DTC management. Data on pregnancy outcome in DTC patients indicate that after conceiving, these women may need an increased L-T4 dose to maintain suppressed serum TSH levels. Nevertheless, this does not determine major harm in terms of pregnancy outcome. Analogously, the most recent findings obtained with the propensity score matching approach have confirmed that pregnancy does not significantly affect DTC clinical course and eventually tumor prognosis. A recent metanalysis and a large case-control study excluded a significant effect of radioactive iodine treatment (RAIT) on several reproductive variables in DTC patients, providing reassuring evidence that the current recommendations on RAIT for women of childbearing age are sufficiently well tolerated and do not affect fertility nor pregnancy rate. Overall, the most recent studies have provided sufficiently reassuring evidence that the occurrence of pregnancy and DTC management are of no reciprocal harm for adverse outcome in affected women of childbearing age. Thus, female DTC patients should be managed according to the individual response to treatment before pregnancy. When DTC diagnosis is made after conception, delaying surgery does not represent a harm in most patients.

Association between TSH and creatinine levels in patients with hypothyroidism

Association between TSH and creatinine levels in patients with hypothyroidism

A screening study of high-risk groups for liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease

The purpose of this study was to explore the correlation between Hashimoto’s thyroiditis and Metabolic dysfunction-associated fatty liver disease (MAFLD), and at the same time to screen high-risk groups for liver fibrosis in MAFLD, find out the high-risk related indicators. The physical examination population was included as the study subjects and was grouped according to the diagnostic criteria for MAFLD. APRI > 1 or NFS > 0.676 or FIB-4 > 2.67were used to assess people at high risk of liver fibrosis, and logistic regression analysis was used to identify risk factors associated with high risk of liver fibrosis in MAFLD. ROC curves are used to look for indicators of diagnostic value. The proportion of people with Hashimoto’s thyroiditis was lower in the MAFLD group. The MAFLD high-risk group for liver fibrosis had higher TSH levels, lower FT3 and FT4 levels, higher TGAB levels, and differences in biochemical markers. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients. ROC curve analysis showed that the AUC of age was 0.741 (0.721–0.761), and the optimal stage value was 57.5 years, while the AUC of AST was 0.729 (0.707–0.751), and the optimal cut-off value was 39.5 U/L. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients.The age is greater than or equal to 57.5 years, or the AST is greater than or equal to 39.5 U/L, indicating that the MAFLD patients are at high risk of liver fibrosis.

Early life air pollution exposures and thyroid function in children: A prospective cohort study

Studies on early life ambient air pollution exposures and childhood thyroid function are scarce. This study aimed to evaluate the relationships between early life fine particulate matter (≤2.5 μm; PM2.5) and nitrogen dioxide (NO2) exposures and thyroid function in children. We measured the levels of thyrotropin, triiodothyronine, and free thyroxine in children (n = 684) residing in a rural Korean area at age 2, 4, 6, or 8 years from 2012 to 2020 in the Environment and Development of Children cohort. The relationship between residential average exposure levels of PM2.5 and NO2 during pregnancy and 1-year average levels before visit and thyroid function during childhood were analyzed. Inverse association between increases of 10 μg/m3 in PM2.5 during the first trimester and thyrotropin levels at aged 4 (β, −0.12; 95% CI: −0.22, −0.02) and 6 years (β, −0.16; 95% CI: −0.26, −0.06) were observed. No association was found between PM2.5 exposure during the second and third trimester and childhood TSH levels. Childhood PM2.5 exposure was positively associated with thyrotropin rise at aged 4 (β, 0.2; 95% CI: 0.06, 0.35) and 6 years (β, 0.16; 95% CI: 0.02, 0.29) and inversely related with free thyroxine levels at aged 8 years (β, −0.04; 95% CI: −0.07, −0.01). No relationship between NO2 exposure and thyroid function was found. In conclusion, association between PM2.5 exposure and childhood thyrotropin levels varied depending on exposure timing. Early gestational exposure showed an inverse relationship, whereas childhood exposure were positively associated with childhood thyrotropin levels. The long-term effects of early life air pollution exposure and underlying mechanisms should be investigated in future studies.

Association of pre-op TSH levels with Thyroid Carcinoma in a Tertiary Care Setup in Karachi, Pakistan

Objectives: This study aimed to explore the relationship between pre-operative TSH levels and the presence of thyroid cancer in patients with nodular thyroid disease in the Pakistani population, using data gathered from patients treated at Dr. Ruth K. M. Pfau Civil Hospital Karachi. Study Design & Setting: A cross-sectional study was conducted at the Dow University of Health Sciences and Dr. Ruth K. M. Pfau Civil Hospital Karachi from January 2022 to December 2022. Methodology: Patients with thyroid swellings (presenting with either solitary nodules or with multinodular goiter), both benign as well as suspected/confirmed malignancy based on FNAC results were recruited in the study. Preoperative TSH levels, along with other clinical data, were collected. Thyroidectomy was carried out in patients fulfilling the criteria for surgery, with specimens sent for histopathology. An independent t-test was used to compare TSH levels between malignant and benign nodules. Results: A total of 82 patients were enrolled. Malignancy was confirmed in 41.5% (25 papillary carcinoma, 9 follicular carcinoma). Significantly higher mean TSH levels were observed in patients with malignant nodules (4.76 IU/mL) compared to those with benign nodules (2.48 IU/mL) (p < 0.001). Conclusion: This study suggests a potential association between elevated pre-operative TSH levels and thyroid cancer in the Pakistani population. These findings warrant further investigation to explore causality and potential underlying mechanisms. The study highlights the value of TSH monitoring, particularly in resource-constrained settings.

Evaluation of zinc oxide nanocomposites and L-ascorbic acid on meat quality during transport induced stress in birds of Sonali breed

The study assessed the efficacy of phytofabricated zinc oxide nanoparticles (CF-ZnONPs) and L-ascorbic acid in alleviating pre-slaughter transport induced stress in birds of Sonali breed (Cross bred of Rhode Island Red cocks and Fayoumi hens). A total of 120 birds were divided into four groups: negative control (T1) which were loaded in vehicle but not transported, Positive control (T2) birds were transported without any prior supplementation, T3 and T4 birds were transported with prior supplementation (a day before transportation) of CF-ZnONPs @100 µg/ml and L-ascorbic acid @82 µg/ml in drinking water. Results obtained observed significant reduction in live weight, meat colour and pH but increased drip loss percentage in T2 group. Significantly elevated H/L ratio was recorded in all transported groups. Increased cortisol and TSH levels and decreased thyroid hormones, Triiodothyronine and thyroxin (T3 and T4) levels were recorded in T2 group. However, supplementation with CF-ZnONPs and L-ascorbic acid notably reversed these adverse effects, restoring meat quality and other metabolic profiles. Notably, ascorbic acid exhibited greater efficacy, suggesting its superior role in mitigating transportation-induced stress. Overall, these findings highlight the importance of antioxidant supplementation in alleviating transport induced stress in birds.

7618 Thyroid Nodules, Normal Thyroid Levels, and Chronic Anxiety: A Case for Sub-Clinical Toxic Multinodular Goiter

Abstract Disclosure: C.M. Barrera: None. Introduction: Chronic anxiety and panic disorders, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), are the most common psychiatric conditions. Hyperthyroidism is a known cause of both chronic anxiety and panic disorder. Case 1: A 36-year-old overweight Latin female is referred for evaluation of multiple thyroid nodules. The thyroid ultrasound was heterogeneous, with multiple bilateral nodules. In her history, the patient has chronic anxiety with panic attacks resulting in frequent emergency room visits. The TSH and T4 levels were TSH 0.59 mIU/L (0.40-4.5) and T4 10.7 mcg/dL (5.1-11.9). An I[1]23- Thyroid Scan showed a hot nodule with mild suppression and an uptake of 31.8% (The top limit is 35%). The patient started methimazole 2.5 mg daily, and after two months, her chronic anxiety and panic attacks resolved. Post-methimazole TSH rose to 1.18 mIU/L, and T4 10.0 mcg/dL and she has weaned off anxiety medications. Case 2: A 49-year-old overweight Latin female is referred for increased thyroid nodules. She complained of six months of tachycardia and anxiety. The TSH and T4 levels were TSH of 0.828 mIU/L (0.40-4.5) and T4 of 7.9 mcg/dl (4.5-12.0). An I[1]23-Thyroid Scan showed no dominant hot or cold nodules, with an uptake of 36.4% (The top limit is 35%, within normal error limits). She started methimazole 5 mg daily, resolving her tachycardia and anxiety within five weeks. Post-methimazole TSH was 1.64 mIU/L (0.45-4.5), and T4 6.7 mcg/dL (4.5-12.0). Case 3: A 60-year-old overweight Latin female is referred for evaluation of multiple thyroid nodules of ten years. She complained of chronic anxiety and panic attacks for two years. The TSH and T4 were normal at TSH 0.36 mIU/L (0.35- 5.50) and T4 9.7 mcg/dL (4.5-10.9). The thyroid ultrasound showed multiple bilateral nodules. An I[1]23-Thyroid Scan showed a suspected hot nodule without appreciable suppression and an uptake of 33% (The top limit is 35%). The patient started methimazole 5 mg daily. After eight weeks, she reported the resolution of most of her chronic anxiety with post-methimazole TSH 2.39 mIU/L and T4 7.1 mcg/dL (4.5-12.0). Discussion: The normal range of TSH, typically from 0.4-4.5 mIU/L, is calculated by measuring the TSH levels among a normal population. The group range then determines the laboratory reference range. This contrasts with individual values, which have a narrower range, suggesting that each person has a unique thyroid level. This suggests that TSH levels at the extremum, associated with hyperfunctioning nodules contributing to a rise in uptake, may not be normal for that patient and may explain the anxiety and other symptoms. Learning Points: Evolving multiple autonomous thyroid nodules lowers TSH levels while raising thyroid uptake. Symptoms of chronic anxiety and panic attacks can predate abnormal thyroid levels and resolve with low-dose methimazole. Presentation: 6/1/2024

12217 Exploring Thyroid-stimulating Hormone As A Potential Cardiovascular Disease Risk Marker In Euthyroid Individuals

Abstract Disclosure: A.P. Neto: None. H. Lucchesi: None. C.C. Silva Janovsky: None. I. Bensenor: None. L.S. Ward: None. L.L. Cunha: None. Previous studies have suggested that TSH levels may predict longevity primarily in elderly individuals. Aging is associated with a high prevalence of cardiovascular and metabolic diseases that reduce survival. However, the relationship between serum TSH levels and these conditions, especially traditional cardiovascular risk markers, remains poorly explored. We employed data from the longitudinal multicenter cohort study ELSA-Brasil, which includes workers from five Brazilian Universities, to evaluate thyroid function in 8,452 participants aged between 34 and 75 years, classified as euthyroid and followed for 8.9 ± 0.6 years. The participants were evaluated for the presence of diabetes, hypertension, angina, peripheral arterial disease, and cardiovascular mortality. Additionally, we measured cardiovascular markers, including global cardiovascular risk score, HbA1c, microalbuminuria (mg/dl), LDL levels, and triglyceride levels. Statistical analysis was used to compare TSH levels with clinically relevant outcomes and classical cardiovascular risk markers. We observed that higher TSH levels correlated negatively with global cardiovascular risk (Spearman rank -0.023, p-value=0.038), microalbuminuria (Spearman rank -0.055, p<0.000), and HbA1c (Spearman rank -0.041, p<0.000). However, TSH levels were positively correlated with hypertriglyceridemia (Spearman rank +0.125, p<0.000) but had no relationship with LDL (p >0.05). The appraisal of cardio-metabolic diseases showed that individuals without diabetes had higher TSH levels (1.79 mIU/L, IQR 1.07) than individuals with diabetes (1.71 mIU/L, IQR 1.07). Patients with arteriosclerosis diseases, such as coronary and peripheral arterial disease, had lower TSH levels (1.66, IQR 0.98 and 1.67, IQR 0.94, respectively) than those who did not have these comorbidities (1.79, IQR 1.07, and 1.79, IQR 1.07). Furthermore, TSH levels did not correlate with the incidence of hypertension (p >0.05). Finally, we divided the population into two groups: higher and lower TSH levels based on the median TSH levels (1.78 mIU/L, IQR 1.06). The Kaplan-Meier curve did not show a difference between these groups (p=0.758) in survival after cardiovascular events (08 events in total) during follow-up. In conclusion, our results suggest that higher serum TSH levels in euthyroid individuals are associated with a lower prevalence of metabolic and cardiovascular disease. However, the relatively short observation duration and low frequency of cardiovascular events in our cohort made it difficult to statistically analyze several endpoints, such as survival. Further investigation is necessary to completely understand whether TSH is a cardiovascular risk indicator. Presentation: 6/2/2024

5051 Clinical Correlation between TSH levels and TAU Imaging

Abstract Disclosure: S. Sunil: None. Background: Tau-PET Scan measures brain tau deposition. TSH levels related to cognitive impairment. We analyzed the correlation of TSH levels to tau-PET imaging in a memory clinic. Hypothesis: Tau-PET positivity correlates with lower TSH values in the clinic patients. Objectives: To assess the correlation of tau-PET positivity to TSH levels in memory clinic patients. Method: Retrospective observational chart review study of patients attending a memory clinic in Boston, MA, with TSH levels and tau-PET scan included for analysis. No stratification based on initial or final diagnosis, severity of cognitive impairment, or tracer used. Baseline TSH levels and a binary PET scan result were analyzed with covariates age, sex and race. Analysis done on ‘R’ v. 2.4.0. Pearson correlation estimated TSH levels to tau-PET status. Kruskal Wallis/Chi square tests for relationship of age, sex, gender and education with TSH levels and tau-PET status. ROC analyses and sensitivity/specificity were obtained. Results: Tau PET positivity did not correlate significantly with TSH levels (r= 0.0655, 95%CI -0.388 to 0.494, p=0.78). Conclusion: Tau PET does not correlate with TSH levels, possibly due to a ceiling effect in the mild impairment subjects. Presentation: 6/2/2024

7308 A Case of Thyroid Hormone Resistance Associated With a Novel Mutation in the THRA Gene

Abstract Disclosure: J.A. Siddiqui: None. M. Barbosa: None. V. Fettig: None. C.J. Romero: None. Introduction: Thyroid hormone resistance (THR) is a syndrome leading to decreased response of target organs to thyroid hormone. Normal thyroid hormone action is mediated by thyroid hormone nuclear receptors and is essential for normal development and metabolism. Two isoforms are encoded by the thyroid hormone receptor α and β genes (THRA and THRB). Mutations in THRB are commonly reported with limited cases of THRA mutations. We report a 15-month-old and her mother with a pathogenic variant in the THRα receptor leading to thyroid hormone resistance. CASE: A 15-month-old ex-39-week gestation female was born small for gestational age (birth weight: 2450 grams,3rd %ile and birth length: 17 inches,1st %ile). The newborn screen was normal. She presented with macroglossia, low tone and global developmental delay. She had severe constipation complicated by rectal prolapse that required surgical correction. There are multiple relatives (mother, maternal half-brother and maternal grandparents) with neurodevelopmental issues. The mother’s previous genetic evaluation was non-diagnostic. Mother reports a thyroid condition but without treatment. The patient was initially referred to genetics and whole exome sequencing revealed a heterozygous c.1205 T>C p. (L402P) variant in the THRα gene, which was maternally inherited and reported as a variant of uncertain significance. On physical exam, Heart rate was 112 bpm; height <1%ile (Z-score -3.22 SD), weight 3%ile (Z-score -1.89 SD). Patient has a wide anterior fontanelle (4x3 cm), macroglossia and delayed teeth eruption. Other exam findings: non-palpable thyroid and postaxial polydactyly on the 5th digit of the right toe. Thyroid hormone testing: normal TSH 1.829 uIU/mL, low total T4 4.4 mcg/dL, low Free T4 of 0.58 ng/dL and high free T3 of 4.24 pg/mL. Levothyroxine treatment was initiated(25 mcg daily). After 1 month treatment, TSH level was 0.23 uIU/mL, total T4 was 6.1 mcg/dL and low reverse T3 of 5.8 ng/dL. DISCUSSION: Thyroid hormone resistance due to THRα mutations are rare and under-recognized. The main clinical phenotype includes growth retardation, delayed development, decreased muscle tone, delayed tooth eruption and constipation. Unlike patients with THRβ mutations, the hypothalamus-pituitary-thyroid axis in patients with THRα mutations is minimally affected with a normal TSH level. Total T3 levels are elevated with slightly low total T4 and free T4:T3 ratio is low. Treatment with levothyroxine leads to suppressions of TSH levels, therefore confirming intact central T3 feedback loop. Reports, however, show minor clinical improvements with treatment; therefore further research is needed in these patients to explore more effective therapeutic options. We present a case of a novel congenital THRA mutation leading to a clinical phenotype consistent with THR. She continues care in our clinic with hopes to further study her mutation. Presentation: 6/2/2024

8124 Prevalence and Characteristics of Patients with Hypothyroidism in the Danish Blood Donor Study

Abstract Disclosure: N.L. Frisk: None. J.R. Shorter: None. O.B. Pedersen: None. L.T. Dalgaard: None. Introduction: While impaired thyroid function leading to subclinical hypothyroidism and overt hypothyroidism is common in Denmark, the knowledge about the paths by which patients’ progress to impaired thyroid function is limited. Undiagnosed hypothyroidism as well as subclinical hypothyroidism constitute serious risk factors for development of cardio metabolic disease. The Danish Blood Donor Study (DBDS) is a large longitudinal cohort and biobank containing information and samples dating more than 10 years back. Blood donors donate blood every 3-6 months and each time provide a sample for research. Research question: The aim of the study was to obtain up-to-date information about prevalence and characteristics of patients with hypothyroidism in a Danish longitudinal cohort of blood donors. Methodology: The study employed a cross-sectional design. Hypothyroidism was defined based on at least two prescriptions of levothyroxine (LT4) and used for calculations of prevalence. Case numbers were compared to all controls that were currently not being prescribed LT4 nor anti-thyroid drugs (carbimazole, propylthiouracil, thiamazole). We compared cases of hypothyroidism to two different control (ctrl) groups: 1) All the participants of the DBDS having TSH levels in the normal range, and 2) Normothyroid participants matched to hypothyroid cases based on age and sex. Incidence was determined based on DBDS participants developing hypothyroidism after being enrolled into the DBDS during a 10-year follow-up. Men and women were compared separately among cases and controls. Students’ t-test was used to compare cases and controls, and corrected using Bonferroni. Major results: There were 3397 cases of hypothyroidism and 153791 ctrl subjects in the DBDS, giving a prevalence of 2.2%. 85% of cases were female, while among ctrl 50% were female. Average age of cases was 52±13 years (mean±SD) for women and 58±13 for men, while ctrls were 45±13 and 48±14 years, respectively (both P<0.001). BMI among cases were: 25.8±4.7 for women and 26.8±3.9 kg/m2, while cases were 25.1±4.4 and 26.0±3.6, respectively (both P<0.001). TSH levels were, for female cases: 4.6±4.0 iu/mL and 5.7±4.9 for men, while ctrls were 1.8±1.1 and 1.7±1.1, respectively (both P<0.001). Free (F) T4 levels were, for female cases: 14.4±6.4pmol/L and male: 14.0±4.6, while ctrls were: 14.8±4.5 and 15.0±3.9 respectively (P<0.003 for females, P<0.0001 for males), while FT3 levels were for cases: 4.3±1.7 and 4.3±1.4 pmol/L and 4.5±2.0 and 4.7±1.5 for ctrls (both P<0.0001). Conclusion: Hypothyroidism is less prevalent among blood donors than reported in the general Danish population, which is accordance with ‘the healthy donor’ bias. Hypothyroid donors were on average older and with higher BMI than normothyroid controls. Donors with hypothyroidism were generally well regulated, but despite that FT4 and FT3 levels were lower than ctrls. Presentation: 6/1/2024

8500 Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter

Abstract Disclosure: A. Batistuzzo: None. B. Bocco: None. E. McAninch: None. M.O. Ribeiro: None. A.C. Bianco: Consulting Fee; Self; Abbvie. Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter Introduction: The Thr92Ala-DIO2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least one polymorphic allele. Ala-D2 is ectopically located in the Golgi apparatus and causes endoplasmic reticulum (ER) stress. It is also about 40 % less active than Thr92-D2, thus T3 production could be compromised in carriers of the polymorphism. Objective: C57BL/6J (B6) mice carrying the Ala92-DIO2 polymorphism exhibit no significant thyroid phenotype as compared to control Thr92-Dio2 mice. Here we wished to test whether changing the genetic background of mice can influence the thyroidal impact of the Thr92Ala-DIO2 polymorphism. Therefore, we backcrossed B6-Thr92Ala-Dio2 mice to the FVB/Ant background for 8 generations. Methods: Mice were killed by asphyxiation in a CO2 chamber and blood collected from 7-18 weeks old female and male FVB/Ant Ala-Dio2 mice to measure plasma levels of TSH, T4, T3, and rT3. The thyroid gland was dissected, weighed and processed for histological analysis. The weight of the thyroid gland was normalized by femoral length. The QuPath Software was used for measuring follicular area, cell height, and the number of internalized follicular cells. Thr92-Dio2 mice of the same age and sex were used as controls. Data were analyzed using PRISM software and expressed as mean±SE (TH plasma levels and thyroid weight) or mean±SD (thyroid histology). A Student t-test was used to compare 2 groups. Results: Male and female Ala mice had significantly higher levels of TSH (males: 0.36±0.04 vs 1.1±0.21 ng/ml; p<0.01 and females: 0.017±0.006 vs 0.12±0.06 ng/ml; p<0.01), lower levels of plasmatic T4 (males: 2.9±0.2 vs 1.3±0.25 µg/dl; p<0.01 and females: 2.1±0.16 vs 1.15±0.16 µg/dl; p<0.001) and lower levels of rT3 (males: 23.8±2 vs 14.2±1.3 ng/dl; p<0.001 and females: 16.45±1.4 vs 10.4±1.17 ng/dl; p<0.01). Additionally, the thyroid gland of female polymorphic mice was heavier (4.3±0.39 vs 1.8±0.17 mg/cm; p<0.001) and both sexes presented enlarged thyroid follicle area (males: 1464±1464 vs 2055±2443 µm2; p<0.0001 and females: 1519±1364 vs 2597±2624 µm2; p<0.0001) and a higher number of internalized follicular cells (females: 0.06±0.007 vs 0.17±0.008 internalized cells/follicle; p<0.0001). No differences in the follicular cell height were observed. Discussion: In contrast to B6, FVB mice carrying the Thr92Ala-D2 polymorphism exhibit goiter, increased follicular area, slightly reduced serum T4 levels, and elevated serum TSH levels. These findings suggest that the impact of the Thr92Ala polymorphism varies according to the genetic background. They may explain why clinical studies of patients carrying the Thr92Ala-DIO2 polymorphism have yielded inconsistent results when different populations are analyzed. Presentation: 6/3/2024