Euthyroid Controls Research Articles

Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.

Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure, which increases the risk of adverse events. This study examined the effects of thyroid hormones (THs) on cardiac transverse-tubule (TT) integrity, Ca2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC) coupling, including L-type calcium channel (CaV1.2), ryanodine receptor type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 wk; followed by randomization to continued PTU without or with oral triiodo-l-thyronine (T3; 10 µg/kg/day) for an additional 2 wk (PTU + T3). Confocal microscopy of isolated cardiomyocytes (CMs) showed significant misalignment of TTs and increased Ca2+ sparks in thyroid-deficient CMs. Density-based spatial clustering of applications with noise (DBSCAN) analysis of stochastic optical reconstruction microscopy (STORM) images showed decreased (P < 0.0001) RyR2 cluster number per cell area in PTU CMs compared with euthyroid (EU) control myocytes, and this was normalized by T3 treatment. CaV1.2 channels and Jph2 localized within a 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither CaV1.2 nor Jph2, suggesting fewer functional clusters in EC coupling. Nearest neighbor distances between RyR2 clusters were greater (P < 0.001) in PTU cells compared with EU- and T3-treated CMs that correspond to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and colocalization of CaV1.2 and Jph2 in optimizing EC coupling.NEW & NOTEWORTHY Thyroid hormone (TH) dysfunction exacerbates preexisting heart conditions leading to an increased risk of premature morbidity/mortality. Triiodo-l-thyronine (T3) optimizes cardiac excitation-contraction (EC) coupling by maintaining myocardial T-tubule (TT) structures and organization of calcium ion channels. Single-molecule localization microscopy shows T3 effects on the clustering of ryanodine receptors (RyR2) with colocalization of L-type calcium channels (CaV1.2) and junctophilin-2 (Jph2) at TT-SR structures. Heart disease with subclinical hypothyroidism/low T3 syndrome may benefit from TH treatment.

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024

7404 Evaluation Of Cortisol Reserve And Adrenal Imaging In Patients With Graves’ Disease Before And Six Months After Treatment

Abstract Disclosure: P. Sharma: None. S. Mir: None. S. Mohd Patto: None. A.H. Bhat: None. B. Dar: None. M. Bhat: None. Introduction: There is scarcity of data regarding the effect of thyrotoxicosis on cortisol metabolism and adrenal gland size. An increase in cortisol metabolism can deplete the functional reserve of adrenal cortex and lead to adrenocortical insufficiency even when there is no pre-existing Addison's disease. In developing countries patients with Graves’ disease present in advanced states of thyrotoxicosis. Besides they are also exposed to a variety of environmental stresses such as recurrent febrile illnesses, salt, and water loss due to manual labour in hot and humid climates etc., which can precipitate an adrenal crisis in the presence of compromised adrenal reserve. So present study was undertaken to assess cortisol reserve and adrenal gland size in patients with treatment naive Graves' disease. Objectives- The present study, was undertaken to assess cortisol reserve and adrenal imaging in patients with treatment naive Graves' disease. Specific information in this regard would help alert physicians dealing with clinical thyrotoxicosis in developing countries of tropics to the possibility of co-existing adrenal decompensation and adopt appropriate life saving measures promptly. Material &amp; Methods: We examined 38 treatment-naive Graves' Disease patients at GMC, SSH, Srinagar, Kashmir, INDIA. Basal cortisol and cortisol response to ACTH were measured before and after six months of treatment, alongside adrenal CT imaging. Results: In hyperthyroid state, Graves' patients exhibited significantly lower basal cortisol compared to euthyroid and healthy controls (306 vs. 410 vs. 421 nmol/l, p &amp;lt; 0.05). 23.6% patients had subnormal cortisol response to ACTH(250ug). Those with T3 ≥ 400 ng/dl had lower cortisol response (560±133 nmol/l) and delta cortisol response than T3 &amp;lt; 400 ng/dl (724 ± 294 nmol/l, 213+/-73 vs. 428+/-265 nmol/l). After achieving euthyroid state, cortisol levels improved significantly (410±213 nmol/l vs. 306 ± 103 nmol/l, p &amp;lt; 0.05). Adrenal CT scans in 34 patients was done out of which 19 showed statistically significant increases in gland thickness, width, and AP diameter compared to controls (p &amp;lt; 0.01, p &amp;lt; 0.05. Repeat CT in 26 patients demonstrated resolution of hyperplasia (p &amp;lt; 0.05). Conclusion: Treatment-naive Graves' disease patients have compromised adrenocortical reserve and adrenal gland enlargement. Adrenal changes are reversible after achieving euthyroid state. These findings support steroid supplementation in impending thyrotoxic crisis and highlight a unique feature of reversible adrenal gland enlargement in this context. Keywords: Graves’ Disease, Adrenal hyperplasia, Cortisol reserve. Presentation: 6/3/2024

Frequency of Dyslipidemia in Patients Having Subclinical Hypothyroidism

OBJECTIVES To determine the lipid abnormalities in subclinical hypothyroidism. METHODOLOGY A case-control study was conducted on euthyroid and subclinical hypothyroid patients presenting to OPD and medical wards of Hayatabad Medical Complex from January to December 2023. The euthyroid control arm had no history of thyroid disease in the past. These hundred control patients were compared to a hundred cases who had subclinical hypothyroidism. All the patients underwent laboratory tests for thyroid hormones and lipid levels. Overt hypothyroidism was excluded. All the results were compared using SPSS statistical analysis version 23. RESULTSWe found that in subclinical hypothyroidism, high triglycerides (TG) were the only abnormal findings, while total cholesterol (TC) and high-density lipoproteins (HDL) were not affected. The risk of hyper triglyceridemia with thyroid stimulating hormone (TSH) levels ≥10mIU/L was 2-fold higher compared to that in the average population (P&lt;0.05).. CONCLUSION Disorders of TG metabolism with subclinical hypothyroidism show a direct correlation with the level of TSH, and the risk of hypertriglyceridemia is moderately increased when the level of TSH ≥10mIU/L. SCH does not affect the level of TC and HDL.

Myxedema in Both Hyperthyroidism and Hypothyroidism: A Hormetic Response?

Myxedema is a potentially life-threatening condition typically observed in severe hypothyroidism. However, localized or diffuse myxedema is also observed in hyperthyroidism. The exact cause and mechanism of this paradoxical situation is not clear. We report here the analysis of body fluid distribution by bioelectrical impedance analysis (BIA) in 103 thyroid patients, subdivided according to their functional status. All BIA parameters measured in subclinical thyroid dysfunctions did not significantly differ from those observed in euthyroid controls. On the contrary, they were clearly altered in the two extreme, opposite conditions of thyroid dysfunctions, namely overt hyperthyroidism and severe hypothyroidism, indicating the occurrence of a typical hormetic condition. Surprisingly, differences in BIA parameters related to fluid body composition were even more evident in hyperthyroidism than in hypothyroidism. A hormetic response to thyroid hormone (TH)s was previously reported to explain the paradoxical, biphasic, time- and dose-dependent effects on other conditions. Our results indicate that myxedema, observed in both hypothyroid and hyperthyroid conditions, represents another example of a hormetic-type response to THs. BIA offers no additional valuable information in evaluating fluid body composition in subclinical thyroid dysfunctions, but it represents a valuable method to analyze and monitor body fluid composition and distribution in overt and severe thyroid dysfunctions.

PSI-21 Limited impact of hypothyroidism on porcine fetal growth during mid to late gestation

Abstract In the fetal pig, both circulating thyroid hormone and growth rate are known to increase throughout gestation; however, the functional association between these coincident factors has not been established. Thus, the objective of this project was to investigate this cause-and-effect relationship by evaluating the impact of induced fetal hypothyroidism on fetal growth during mid to late gestation. To induce fetal hypothyroidism, n = 12 pregnant gilts were orally treated with the goitrogen methimazole (MMI) at a dose of 5 mg/kg/d for 21 d, with n = 3 gilts starting treatment on gestation d 34, 45, 55 and 65. An equivalent group n = 12 of gilts were sham treated for the same periods to produce gestationally age-matched euthyroid control litters (CON). Upon completion of the treatment period, gilts were humanely euthanized, and the resulting populations of n = 174 MMI and n = 166 CON fetuses deeply phenotyped. No meconium-stained fetuses were observed at any time point, and only 5 mummified fetuses were observed (3 CON, 2 MMI), indicating treatment has no effect on fetal viability. Fetal body weight (BW) and the weights of individual organs including thyroid, liver, heart, lung, kidney, spleen, and brain were collected. In addition, fetuses were imaged in both left and right lateral recumbency for subsequent morphometric assessment using a custom analysis pipeline in ImageJ. Image analysis yielded parameters including crown-rump length, girth, brow length, depth at the snout/skull junction, depth at the snout/nose junction, and area under the skull curvature (AUC). Left and right measurements for all morphometric parameters were found to be highly correlated (r2 &amp;gt; 0.9) indicating a repeatable measure using this approach. Statistical analysis of all phenotypic differences was carried out using a linear mixed effect model including gestational age and treatment as fixed effects and gilt as a random effect. A significant increase in both absolute and relative thyroid weights indicated the development of goiter and thus, successful induction of hypothyroidism within the MMI litters. In addition, a significant treatment by time interaction was observed, with 0.014 g and 0.21 g increase at d 55 and 66, respectively, indicating reduced compensatory action within the fetal hypothalamic-pituitary-thyroid axis during this earliest period. Liver weight as a percentage of BW decreased from 6.06% to 2.56% between d 55 and 86 in the CON group but was significantly increased at all time points in response to MMI induced hypothyroidism (P &amp;lt; 0.01). A corresponding increase in brain to liver weight ratio over time was suppressed in MMI fetuses (P &amp;lt; 0.05). While all other phenotypic parameters were significantly altered by gestational age, there was no significant impact of fetal hypothyroidism. Collectively, the results indicate that fetal growth during mid to late gestation is not driven by fetal thyroid hormone.

Evaluation of systemic inflammation markers in patients with Hashimoto's thyroiditis.

To investigate markers of systemic inflammation and the effect of thyroid dysfunction on these parameters in patients with Hashimoto's thyroiditis (HT). Patients with HT and volunteer healthy individuals admitted to the general surgery outpatient clinic between January 2020 and June 2023 were enrolled into the study. Patients with HT were divided into euthyroid, hypothyroid, and hyperthyroid subgroups. All participant data were retrospectively extracted from the hospital database. A total of 268 patients (euthyroid, n = 131; hypothyroid, n = 83; and hyperthyroid, n = 54) and 124 controls were included. The platelet-to-lymphocyte ratio was lower in the euthyroid group versus control group, and the neutrophil-to-lymphocyte ratio was lower in controls than the three patient subgroups. Euthyroid and hypothyroid patients with HT exhibited a higher systemic inflammation index than the control group. The pan-immune inflammation index was lower in controls than in euthyroid, hypothyroid, and hyperthyroid patients with HT. In patients with HT, inflammation markers did not significantly differ between subgroups. Markers of systemic inflammation provide meaningful and reliable information in patients with HT, but do not differentiate between euthyroid, hypothyroid, or hyperthyroid patients.

Assessment of Plasma Homocysteine in Patients with Hypothyroidism in a Nigerian Tertiary Hospital

Introduction: Hypothyroidism, a risk factor for atherosclerotic cardiovascular disease has been seen to be associated with hyperhomocysteinemia. The plasma levels of homocysteine and its relationship with hypothyroidism was assessed. Material and Methods: A total of 120 patients aged 20 – 60 years comprising of 60 hypothyroid and 60 euthyroid controls were assessed for the study. Evaluation of plasma homocystein was done using human homocysteine ELISA my BioSource. FT3, FT4 and TSH were also evaluated by enzyme linked immunosorbent assay (ELISA) technique using stat fax-2100. Result: In our study, we have found the values of FT3 in the subjects as 1.21+ 0.89pg/ml lower than controls values of 1.92+0.66pg/ml, values of FT4 in subjects as 0.60+0.53ng/dl as compared to control group value of 1.40+0.30ng/dl, values of TSH as 2.07+1.19µiU/ml higher than the control group of 0.48+1.67µiU/ml. The mean values of plasma homocysteine (Hcy) for subjects was 34.50+10.01µmol/L higher than the control group with 9.30+2.11µmol/L. Conclusion: Our study findings suggest that patients with hypothyroidism also have a high plasma homocysteine known to pose cardiovascular complications.

P-610 Elevated/high-normal TSH on day of beta-hCG in sub-clinical hypothyroid patients on levothyroxine associated with better odds of pregnancy in IVF cycles: a nested case-control study

Abstract Study question Is there an association between odds of achieving pregnancy and high-normal/elevated TSH levels in sub-clinical hypothyroid (SCH) patients on levothyroxine replacement who are undergoing IVF? Summary answer Odds of achieving pregnancy are significantly greater when TSH on day of beta-hCG is elevated/high-normal despite levothyroxine replacement in sub-clinical hypothyroid (SCH) patients undergoing IVF. What is known already TSH levels are known to increase following ovarian stimulation (OS). A 2023 Nature publication reported that in euthyroid patients undergoing fresh embryo transfer following OS and IVF, elevated/high-normal TSH levels (&amp;gt;2.5 mIU/mL) are associated with better pregnancy rates. Another recent study found no differences in IVF outcomes between SCH patients whose TSH was maintained=/&amp;lt; 4.2 mIU/mL on levothyroxine vs euthyroid controls. To the best of our knowledge, there are no prospective studies investigating possible association between pregnancy outcome and elevated TSH levels following OS within a cohort of SCH patients on levothyroxine replacement, using 2.5 mIU/mL as a strict cut-off. Study design, size, duration Nested case-control study performed between July-December 2023. PCOS and other endocrinopathies excluded. 100 SCH patients booked for fresh, blastocyst eSET cycles initially recruited after thyroxine replacement. 79 patients completed the study following 5 drop-outs and 16 cases of cycle cancellation/failure, cleavage-stage transfers and freeze-all. Odds of achieving pregnancy (‘cases’) in patients with elevated/high-normal TSH (‘exposure’) on day of beta-hCG determined by Odds Ratio, with beta-hCG negative patients serving as ‘controls’. First IVF cycle data analysed/presented. Participants/materials, setting, methods Study performed at an university-affiliated ART institute. Following institutional ethical clearance, patients with SCH (TSH&amp;gt;2.5 mIU/mL) recruited after informed consent. Levothyroxine replacement initiated to achieve TSH:0.5-2.5 mIU/mL and continued; followed by OS, antagonist IVF/ICSI cycles, hCG trigger and fresh blastocyst eSET. TSH measured again on day of beta-hCG (blinded). Odds Ratio calculated (IBM SPSS V.26) to determine odds of achieving pregnancy in high-normal/elevated group (TSH&amp;gt;2.5 mIU/mL) compared to low-normal group (TSH =/&amp;lt; 2.5 mIU/mL). Main results and the role of chance Baseline demographic characteristics of the single starting cohort of sub-clinical hypothyroid patients undergoing IVF/ICSI (n = 79) are summarized as mean±SD- age: 31.7±4.9 years, BMI: 27.9±14.2 kg/m2, AMH: 3.1±2.4 ng/mL, TSH before levothyroxine replacement: 5.5±2.7 mIU/mL. Data analysis showed that out of 63 patients in whom TSH level elevated &amp;gt; 2.5 mIU/mL on day of beta-hCG, 33 became pregnant (P.R- 52.4%); and out of 16 patients in whom TSH remained =/&amp;lt; 2.5 mIU/mL on day of beta-hCG, 3 became pregnant (P.R- 18.8%). Statistical analysis further revealed that odds of achieving pregnancy in elevated/high-normal TSH group was almost 5 times compared to odds of achieving pregnancy in low-normal TSH group (OR = 4.77, C.I= 1.24-18.37, at 95% confidence), considering TSH values on day of beta-hCG. Mean TSH in pregnant group (n = 36) was also found to be higher (4.2±1.6 mIU/mL) than mean TSH (3.9±1.9 mIU/mL) in those who did not get pregnant (n = 43). Limitations, reasons for caution Our study is limited by its modest sample size and adequately powered, larger prospective studies are needed before definite conclusions can be drawn from our data. Moreover, being an ongoing study, we do not yet have miscarriage and live-birth data for all patients and thus have not reported the same. Wider implications of the findings To our knowledge, this is the first prospective study documenting association between positive pregnancy outcome and high-normal TSH (using TSH&amp;gt;2.5 mIU/mL as cut-off) in SCH patients having fresh blastocyst eSET. Further investigation is required to determine if high-normal TSH following OS has protective impact on IVF, and its underlying mechanism. Trial registration number not applicable

A study of the association of lipid ratios with thyroid dysfunction in a tertiary medical college in Eastern India

Background: Thyroid hormones play a crucial role in major metabolic pathways in the body and dyslipidemia is a major metabolic abnormality seen in thyroid disorders. Cardiovascular diseases (CVDs) are now emerging as the leading cause of morbidity and mortality worldwide and the most important risk factor for CVDs is dyslipidemia. The lipid ratios that have a positive association with CVD risk are atherogenic index of plasma (AIP), Castelli’s risk index (CRI)-I and II, and atherogenic coefficient (AC). Clinically, both an excess and deficiency of thyroid hormones can exacerbate or induce CVDs and lipid ratio can be used as an inexpensive marker for predicting CVD risk. Aims and Objectives: This study aims to evaluate the lipid ratios (AIP, CRI-I, CRI-II, AC) in patients with thyroid dysfunction and compare the results with lipid ratios in euthyroid individuals. This study also aims to find any correlation, if exists, between lipid ratios and serum thyroid-stimulating hormone (TSH) levels in thyroid dysfunction. Materials and Methods: The serum TSH and lipid profile were evaluated in fifty euthyroid, fifty hypothyroid, fifty subclinical hypothyroid, and fifty hyperthyroid patients. The lipid ratios (AIP, CRI-I, CRI-II, AC) were calculated from the lipid profile. Results: The mean lipid ratios were higher in hypothyroid, followed by subclinical hypothyroid cases when compared to euthyroid controls and hyperthyroid patients. A positive correlation was observed between the TSH and lipid ratios in euthyroid, hypothyroid, and subclinical hypothyroid subjects. There was no significant correlation between TSH and lipid ratios in hyperthyroid patients. Conclusion: This study demonstrates that the evaluation of lipid ratios along with TSH can provide an effective screening tool to assess the cardiovascular risk in patients with subclinical and overt hypothyroidism, especially in the absence of imaging techniques in resource-limited centers.

Evaluation of the Association between Insulin Resistance and Subclinical Hypothyroidism Using Triglyceride-Glucose Index: a Cross-Sectional Study.

Thyroid disorders and diabetes mellitus are often known to co-exist, implying an interrelationship between thyroid dysfunction and insulin resistance. Triglyceride-glucose (TyG) index is a relatively new surrogate marker of insulin resistance, which is cost-effective and easily calculated with routine lab tests. Data about association of subclinical hypothyroidism (SCH) and insulin resistance, especially with reference to TyG index, is lacking. To evaluate the association of SCH and insulin resistance using the TyG index by comparing its value in patients with SCH and age- and gender-matched euthyroid controls. Also, to determine if there is a correlation between TyG index values and thyroid profile parameters (TSH, FT3 and FT4) in both study groups. Thirty-five patients with SCH and an equal number of age- and gender-matched euthyroid controls were included in the present study. The TyG index was calculated for each group and compared. The correlation between TyG index and thyroid profile parameters (TSH, FT3 and FT4) was also assessed. The TSH values were significantly higher in the SCH group (6.6±1.7 µIU/mL) than the control one (2.5±1.2 µIU/mL; p<0.0001). There was no significant difference in FT3 in the SCH group (2.93±0.49 pg/ mL) and the control one (3.05±0.64 pg/mL; p=0.310). The level of FT4 was also not found to be significantly different in SCH subjects (1.23±0.44 ng/dL) and controls (1.4±0.42 ng/dL; p=0.077). The TyG index values were significantly higher in the SCH group (4.8±0.2) as compared to the control one (4.7±0.2; p = 0.015). The TyG index did not show any significant correlation with the thyroid parameters in any of the two groups. There is a positive association between SCH and insulin resistance in terms of TyG index. This index may thus be helpful in early screening and management of such patients for insulin resistance related conditions like diabetes mellitus, metabolic syndrome and cardiovascular disorders.

Serum Selenium Level in Thyroid Cancer: A Case-Control Study.

Despite the implementation of national iodine supplementation programs, structural thyroid diseases are still highly prevalent in most countries. Thus, the link between trace elements other than iodine, such as selenium, and thyroid diseases should be investigated. In this case-control study, adult patients with newly diagnosed papillary thyroid carcinoma, benign thyroid nodules, and healthy euthyroid controls without nodules were recruited. Thyroid function tests and serum selenium levels were assessed and compared between groups. The One-way ANOVA test was used to assess the mean difference of numerical variables among the three studied groups (PTC, Benign nodule, and healthy control group). In addition, a post-hoc comparison was conducted based on Bonferroni correction for a pairwise comparison of these three groups. Data from 182 patients with papillary thyroid carcinoma (PTC), 185 patients with benign thyroid nodules, and 180 healthy individuals as a control group were analyzed. The mean serum selenium levels in the PTC, benign thyroid nodules, and control group were 94.9, 121.6, and 134.3 µg/l, respectively (P < 0.001). There was a significant relationship between the cancer stage and selenium level in the PTC group. Patients in higher stages of cancer had a lower mean of selenium (P < 0.001). In univariate logistic regression, TSH and selenium were significant variables for PTC compared with patients with benign thyroid nodules. Each unit increase in selenium reduces the chance of PTC by about 6%. The low levels of selenium were associated with PTC. Also, serum selenium levels were inversely correlated with the stage of thyroid cancer.

Expression of hTERT and Lp-PLA(2) genes is increased in primary hypothyroidism.

ObjectiveSightly low serum free T4 levels are associated with longer life expectancy. However, hypothyroidism is associated with increased risk of inflammation and vascular complications. Therefore, relation of thyroid hormones (THs) with life expectancy seems to be complex. This study was carried out in an effort to understand the contribution of THs in inflammation and aging. Methodology15 cases of treatment naïve primary hypothyroidism and 15 age and sex matched euthyroid controls were recruited. mRNA expression of Telomerase (hTERT), leucocyte telomere length (LTL) and Lipoprotein associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation and risk predictor of cardiovascular events were measured by qPCR in whole blood. ResultExpression of hTERT was found to be 6.95 times higher in the cases as compared to the controls. mRNA expression of Lp-PLA(2) was also 3.3 times higher in cases. LTL in euthyroid was approximately 81% of the length in hypothyroid patients. ConclusionA higher expression of hTERT indicates that hypothyroidism confers better cell survival in peripheral leucocytes inspite of the presence of vascular inflammation. However causal relationship cannot be ascertained with these results.

The Influence of Hyperthyroidism on the Coagulation and on the Risk of Thrombosis.

Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and immunologic parameters in patients with hyperthyroidism. Methods: Our study consists of a total of 200 patients comprised of 64 hyperthyroid patients, 68 hypothyroid patients, and 68 euthyroid controls. Patient thyroid status was determined with standard tests. Detailed hemostatic parameters and cardiolipin antibodies of each patient were determined. Results: The values of factor VIII (FVIII), the Von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and anticardiolipin antibodies of the IgM class were significantly higher in the hyperthyroid patients than in the hypothyroid patients and euthyroid controls. The rate of thromboembolic manifestations was much higher in hyperthyroid patients (6.25%) than in hypo-thyroid patients (2.9%) and euthyroid controls (1.4%). Among hyperthyroid patients with an FVIII value of ≥1.50 U/mL, thrombosis was recorded in 8.3%, while in hyperthyroid patients with FVIII value ≤ 1.50 U/mL the occurrence of thrombosis was not recorded. The incidence of atrial fibrillation (AF) was significantly higher (8.3%) in the hyperthyroid patients compared to the hypothyroid patients (1.5%) and euthyroid controls (0%). Conclusions: High levels of FVIII, vWF, fibrinogen, PAI-1, and anticardiolipin antibodies along with other hemostatic factors contribute to the presence of a hypercoaguable state in patients with hyperthyroidism. The risk of occurrence of thrombotic complications is especially pronounced in patients with a level of FVIII exceeding 150% and positive anticardiolipin antibodies of the IgM class. Patients with AF are at particularly high risk of thrombotic complications due to a hyperthyroid prothrombotic milieu.

Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes.

A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.

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

Hyperthyroidism in humans is associated with a hypercoagulable state and an increased risk of thromboembolism. 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. Client-owned hyperthyroid (n = 16) and euthyroid (n = 15) cats over 8 years of age. 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. 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. 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.

Atherogenic Indices as Early Predictors of Cardiovascular Diseases among Patients with Subclinical and Overt Hypothyroidism in a Tertiary Care Hospital, Karnataka: A Cross-sectional Study

Introduction: Hypothyroidism is a common health issue that decreases the functional ability of life. It is strongly associated with altered levels of serum lipids, leading to an increased risk of Cardiovascular Disease (CVD). Lipid profile and Atherogenic Indices (AIs) can serve as better markers for evaluating CVD risk. Aim: The aim of this cross-sectional study is to evaluate the role of dyslipidaemia and AIs as predictors of CVD risk among patients with Subclinical Hypothyroidism (SCH) and Overt Hypothyroidism (OH) compared to euthyroid controls. Materials and Methods: The present cross-sectional study was conducted at the Clinical Biochemistry Section of Mandya Institute of Medical Sciences in Mandya, Karnataka, India from August to September 2019. A total of 150 subjects aged between 25-60 years were enrolled. Fasting lipid profile and Thyroid Function Test (TFT) were analysed. Based on TFT results, subjects were categorised into SCH, OH, and euthyroid groups. Data on anthropometry {(height, weight, Body Mass Index (BMI), and Blood Pressure (BP)}, lipid profile, Atherogenic Index of Plasma (AIP), Castelli Risk Index-I (CRI-I), CRI-II, and Atherogenic Coefficient (AC) were collected. Statistical analysis was performed using Pearson’s correlation and Receiver Operating Characteristic (ROC) curve analysis. Results: Out of the 150 subjects, 104 (69.3%) were females and 46 (30.7%) were males, with a mean age of 41.08±11.24 years. Both the SCH and OH groups showed statistically significant dyslipidaemic changes and elevated AIs compared to euthyroid controls. Among OH patients, there was a statistically significant positive correlation between TSH and Total Cholesterol (TC) (r=0.463), Low-Density Lipoprotein cholesterol (LDL-c) (r=0.448), CRI-I (r=0.414), CRI-II (r=0.412), and AC (r=0.411). Conversely, there was a statistically significant negative correlation between fT3 and TC (r=-0.393), LDL-c (r=-0.363), CRI-I (r=-0.300), CRI-II (r=-0.301), and AC (r=-0.298). Among the AIs, AIP showed the maximum Area Under the Curve (AUC) in both the SCH (0.707) and OH (0.747) groups. Conclusion: AIs aid in the better assessment of dyslipidaemia and CVD risk compared to lipid profile alone in hypothyroid subjects. Incorporating AIs enables early prediction of high-risk individuals for CVD risk.

Assessment of Serum Cortisol Levels in Hypothyroidism Patients: A Cross-Sectional Study.

Hypothyroidism, characterized by insufficient thyroid hormone production, affects a significant global population, particularly women and the elderly. Recent research has emphasized the interaction between hypothyroidism and the hypothalamic-pituitary-adrenal (HPA) axis, highlighting cortisol's crucial role in the disease's physiological manifestations. This study aims to evaluate serum cortisol levels in hypothyroid patients, examining the intricate relationship between these two endocrine systems. By exploring the potential impact of altered cortisol levels on hypothyroidism's clinical presentation and progression, the study seeks to contribute valuable insights to enhance diagnostic approaches and develop more effective treatment strategies. A cross-sectional observational study was conducted at the Indira Gandhi Institute of Medical Sciences, assessing 65 hypothyroid cases and 65 age-matched euthyroid controls. Demographic data, medical history, and blood samples were collected, and serum cortisol, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels were measured. The study adhered to ethical considerations and received institutional approval. The study included 65 hypothyroid cases (56 females, 9 males) and 65 euthyroid controls. Serum cortisol showed a significant correlation with TSH and T4 levels. Linear regression revealed a negative correlation between serum T4 and T3 levels and serum cortisol in hypothyroidism. A positive correlation was observed between TSH and cortisol. These findings align with previous studies, suggesting potential regulatory mechanisms and compensatory responses in hypothyroid patients. The study's results emphasize the complex interaction between cortisol and thyroid function, suggesting a direct relationship between serum cortisol and TSH levels in hypothyroidism. Patients with severe hypothyroidism exhibited elevated cortisol concentrations, indicating a potential compensatory mechanism initiated by the HPA axis. Integrating serum cortisol assessment with conventional thyroid function tests could offer comprehensive insights into hypothyroidism severity and progression, providing a more holistic approach to patient care. This study contributes to understanding the complex relationship between serum cortisol levels and hypothyroidism, emphasizing the need for further research to uncover underlying mechanisms and therapeutic implications. A comprehensive understanding holds the potential for more tailored and effective treatment strategies for individuals with hypothyroidism.

ASSESSMENT OF COGNITIVE FUNCTIONS AMONG SUBJECTS WITH SUBCLINICAL HYPOTHYROIDISM

Objective: The consequences of overt hypothyroidism on CNS are well known. In contrast, there is less evidence regarding the effects of subclinical hypothyroidism (SCH) on cognitive functions. Studies have shown a variable association between SCH and cognitive dysfunction. This study was done to assess the prevalence of cognitive impairment among subjects with SCH. Methods: The participants were 100 subjects (aged 40-60 years) with SCH and similar number of age-matched euthyroid controls. Subclinical hypothyroidism was defined as serum TSH level &gt; 4.5 mIU/L with normal FT3 and FT4. Participants were interviewed by a single observer. Cognitive function was assessed by mini mental state examination (MMSE) and clock drawing test (CDT). MMSE scores ≤24 is indicative of cognitive impairment. For CDT a score of ≥3 represents a cognitive deficit, while a score of 1 or 2 was considered normal. Results: The mean age of patient group was 47.4 years, and BMI of 26.1kg/m2 which were comparable to controls who had a mean age of 46.1 years (P=0.16) and mean BMI of 25.9 kg/m2 (P=0.25). All other baseline variables including sex ratio, co-morbidities, family history of dementia, smoking, alcohol use, education and exercise were also comparable in both groups. The mean TSH was 7.8 mIU/L in patients and 2.7 mIU/L in controls (P&lt; 0.05). The mean MMSE score was 26.1 in patient group and 27.7 in controls (P=0.31) The patients had mean CDT of 2.32 and controls 2.44 (P=0.61). Cognitive impairment by MMSE (score ≤24) was found in 22.0% of patients and in 16.0% of controls (P=0.14), also the cognitive impairment by CDT (score of ≥3) was present in 27.0% of patients and 25.0% of controls (P=0.29). Conclusion: In the present study we have found that the prevalence of cognitive impairment in subjects with SCH is similar to the age matched controls. Therefore the potential benefit of levothyroxine therapy if used with an aim of improving cognitive functions becomes doubtful.

SAT278 Thyroid Hormones Regulate 11bhsd Enzymes: A Novel Function In Glucocorticoid Hormone Metabolism

Abstract Disclosure: L. Bessiene: None. J. Perrot: None. S. Hescot: None. A. Bourdin-Pintueles: None. G. Vitellius: None. L.M. Sachs: None. P. Kamenicky: None. M. Lombes: None. E. Pussard: None. S. Viengchareun: None. L. Martinerie: None. Glucocorticoid hormone metabolism is regulated by 11-beta hydroxysteroid dehydrogenase enzymes: 11βHSD2, mostly expressed in the distal nephron, converts corticosterone into 11-dehydrocorticosterone in rodents, while 11βHSD1 catalyzes the opposite reaction in liver. Glucocorticoid hormone metabolism may be altered under pathophysiological conditions of hypothyroidism. However, direct functional relationship between glucocorticoid and thyroid hormones (T3) signaling pathways remains elusive. Identification of putative Thyroid Response Elements (TRE) in the promoter regions of hsd11b2 and hsd11b1 genes suggested that T3 might directly regulate expression and/or activity of these enzymes.We used human translational studies, a mouse model of hyperthyroidism and murine renal and hepatic cell lines to investigate the role of thyroid hormones in glucocorticoid hormone metabolism.In hypothyroid patients, the urinary [E]/[F] ratio measured by LC-MS/MS technology, showed a 60% decrease (P&amp;lt;0.05), compared to age- and sex- matched euthyroid controls, suggesting a regulation of glucocorticoid metabolism by T3. Similarly, a significant positive correlation was observed between the urinary [E]/[F] ratio and serum T4L concentration in hyperthyroid patients before and after normalization of T4L levels.Administration of T3 in drinking water, mimicking a mouse model of hyperthyroidism, led to significant increase in renal 11βHSD2 mRNA (P&amp;lt;0.05) and decrease in liver 11βHSD1 mRNA and protein levels (P&amp;lt;0.01), compared to control mice.Finally, T3 induced an increase in 11βHSD2 transcript levels in renal KC3AC1 cells (P&amp;lt;0.01) and a decrease in 11βHSD1 mRNA levels in hepatic HepG2 cells (P&amp;lt;0.01). 11βHSD2 activity increased by 20% (P&amp;lt;0.05). In HEK 293T cells, T3 transactivated hsd11b2 promoter via the Thyroid Receptor α1 (TRα1). ChIP experiments further demonstrated a T3-dependent specific recruitment of TRα1 onto hsd11b2 promoter. Altogether, these findings demonstrate that T3 directly regulate expression and activity of 11βHSD enzymes, thereby controlling glucocorticoid hormone metabolism and action. Presentation: Saturday, June 17, 2023