Subclinical Hypothyroidism Group Research Articles

Subclinical Hypothyroidism Predicted Adverse Cardiovascular Events in Patients with Ejection Fraction Preserved Heart Failure.

Subclinical hypothyroidism (SH) increases the risk of cardiovascular events, however the influence of SH on prognosis of ejection fraction preserved heart failure (HFpEF) is not fully understood. In this prospective observational study, patients with HFpEF were divided into euthyroidism group (n = 413) and SH group (n = 79). Patients were followed up for at least 30 months to examine the association between SH and cardiovascular events in patients with HFpEF. The primary end point was composite cardiovascular events (cardiovascular death and re-hospitalization). The patients underwent flow-mediated dilation (FMD) measurement by ultrasound in order to value endothelial function. The rate of composite cardiovascular events was higher in SH group than in euthyroidism group (54.49% and 26.36%, respectively; p < 0.001). The higher risk of cardiovascular events in SH group was primarily due to a higher risk of re-hospitalization compared to euthyroidism group (45.56% and 20.58%, respectively; p < 0.001). The rate of cardiovascular death was higher in SH group than in euthyroidism group (13.92% and 5.81%, respectively; p = 0.017). Cox proportional hazards regression showed that SH (hazard ratios [HR] 1.921, 95% confidence interval [CI] 1.139-3.240), level of TSH (HR 1.025, 95% CI 1.010-1.054), age (HR 1.017, 95% CI 1.002-1.034), LVEF (HR 0.975, 95% CI 0.953-0.996), atrial fibrillation (HR 1.581, 95% CI 1.083-2.307), eGFR (HR 0.987, 95% CI 0.978-0.997), and NYHA cardiac function (HR 2.342, 95% CI 1.649-3.326) were independent predictors of cardiovascular events in patients with HFpEF (all P < 0.05). Subclinical hypothyroidism was associated with increased cardiovascular events and death in patients with HFpEF.

Fetuin-A level in patients with untreated thyroid dysfunction

Fetuin-A, a plasma glycoprotein, has been demonstrated to play an essential role in the pathogene­sis of several metabolic disorders. This study aimed to estimate fetuin-A serum level in patients with newly diagnosed primary hyperthyroidism (PHT) and subclinical hypothyroidism (SCH) and to examine its correlation with thyroid hormones level, age and sex of patients. The study involved 90 patients with untreated thyroid dysfunction verified with thyroid function test (45 with PHT and 45 with SCH) and 90 control subjects. Triiodo­thyronin (T3), tetraiodothyronin (T4), and thyroid stimulating hormone (TSH) serum concentrations were measured with enzyme-linked fluorescent assay (ELFA), fetuin-A concentration was measured with enzyme-linked immunosorbent assay (ELISA). It was demonstrated that the level of fetuin-A was significantly higher in the PHT group as compared with the control group and showed a significant positive correlation with the T3 level. In the SCH group, the level of fetuin-A was significantly lower and showed a negative correlation with TSH level. Fetuin-A level rose with age in the PHT group and was unaffected by sex in all studied groups. The perfect AUC value obtained for fetuin-A in the comparison between PHT and SCH groups suggests its potential use as a reliable diagnostic marker to differentiate between these two thyroid conditions.

Structural and Functional Alterations of Hippocampal Subfields in Patients with Adult-onset Primary Hypothyroidism.

Hypothyroidism is often associated with cognitive and emotional dysregulation; however, the underlying neuropathological mechanisms remain elusive. The study aimed to characterize abnormal alterations in hippocampal subfield volumes and functional connectivity (FC) in patients with subclinical hypothyroidism (SCH) and overt hypothyroidism (OH). This cross-sectional observational study comprised 47 and 40 patients with newly diagnosed adult-onset primary SCH and OH, respectively, and 53 well-matched healthy controls (HCs). The demographics, clinical variables, and neuropsychological scale scores were collected. Next, the hippocampal subfield volumes and seed-based FC were compared between the groups. Finally, correlation analyses were performed. SCH and OH exhibited significant alterations in cognitive and emotional scale scores. Specifically, the volumes of the right granule cell molecular layer of dentate gyrus (GC-ML-DG) head, CA4 and CA3 head were reduced in SCH and OH groups. Moreover, the volumes of the right molecular layer (ML) head, CA1 body, left GC-ML-DG head, and CA4 head were lower in SCH. In addition, the hippocampal subfield volumes decreased more significantly in SCH than OH. The seed-based FC decreased in SCH but increased in OH compared with HCs. Correlation analyses revealed thyroid hormone (TH) was negatively correlated with FC values in hypothyroidism. Patients with SCH and OH might be at risk of cognitive decline, anxiety, or depression, and exhibited alterations in the volume and FC in specific hippocampal subfields. Furthermore, the reduction in volume was more pronounced in SCH. This study provides novel insights into the neuropathological mechanisms of brain impairment in hypothyroidism.

Assessment of Clinical and Biochemical Cardiac Risk Factors in Patients with Subclinical Hypothyroidism: A Cross-sectional Study

Introduction: Cardiovascular diseases (CVD) are among the leading causes of morbidity and mortality in the current era, and the focus is gradually shifting towards identifying the risk factors and pathways leading to CVD. While hypothyroidism has been extensively studied and linked to CVD risk, the association between subclinical hypothyroidism and CVD risk factors is not well established. Aim: To investigate the association between subclinical hypothyroidism and cardiac risk factors such as obesity indicators {Body Mass Index (BMI) and Waist-hip Ratio (WHR)}, blood pressure, and lipid parameters. Materials and Methods: This cross-sectional study was conducted at the Department of Medicine, ESI PGIMSR, Basaidarapur, New Delhi, India, from December 2020 to April 2022. The study included 200 patients, with 100 patients recruited in the subclinical hypothyroidism group (Thyroid Stimulating Hormone (TSH) &gt;4.8 μIU/mL with normal fT4) and 100 patients with euthyroid status (TSH 0.5-4.8 μIU/mL and normal fT4) included in the comparison group. Both groups were assessed for CVD risk factors including obesity indicators (BMI and WHR), blood pressure, and lipid parameters. The two groups were analysed for statistical significance using Student’s t-test. Results: Both groups had similar age distributions. However, there was a greater percentage of female patients in the subclinical hypothyroidism group (61%) compared to the euthyroid group (52%). As expected, TSH levels in the subclinical hypothyroidism group were significantly higher than in the euthyroid group. The subclinical hypothyroidism group recorded significantly higher mean values of BMI, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), total cholesterol, and triglycerides, which were higher by 18%, 17%, 17%, 41%, and 16% compared to the euthyroid group, respectively. Other parameters like WHR and Low-Density Lipoprotein-Cholesterol (LDL-C) were found to be raised in subclinical hypothyroidism compared to the euthyroid group, while High-Density Lipoprotein-Cholesterol (HDL-C) levels were significantly lower by 16% in subclinical hypothyroidism. Conclusion: Subclinical hypothyroidism is significantly associated with cardiac risk factors like obesity indicators (BMI and WHR), blood pressure, and lipid parameters.

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.

Study of Feto-Maternal Outcome in Pregnancy with Subclinical Hypothyroidism

Background: Hypothyroidism has a great impact on pregnancy. But there is a controversy about the maternal and perinatal outcomes of subclinical hypothyroidism (SCH). This study was placed to know the significant effects. Methods and Materials: A descriptive longitudinal study was held in Z. H. Sikder Women’s Medical College &amp; Hospital, Dhaka, Bangladesh. 400 pregnant women were included in this study with purposive sampling. All antenatal patients from booking visit at 1st trimester to delivery were monitored by serum TSH and serum FT4 levels in each trimester and fetal outcomes were also monitored. 200 pregnant women were diagnosed as subclinical hypothyroidism (SCH) with random screening of initial thyroid function tests. Another 200 pregnant women were euthyroid. The study period was 3 years, from January 2020 to December 2022. To evaluate the thyroid status, maternal serum samples were collected in each trimester, total three times. Maternal outcomes, which we studied, were gestational hypertension, gestational diabetes mellitus, maternal anemia, antepartum hemorrhage, postpartum hemorrhage, placental abruption, preterm delivery, premature rupture of membranes (PROM), caesarean deliveries; perinatal outcomes were low birth weight (LBW), intrauterine growth restriction (IUGR), low Apgar score, stillbirth, congenital anomaly and NICU admission. Result: This study includes 400 pregnant women, among which 200 were euthyroid and 200 were with SCH. The mean age was 27.12 ± 0.05 years in pregnancy with euthyroid group and 26.31 ± 0.25 in pregnancy with SCH group. Among the pregnancy with euthyroid group, 141 women were nullipara and 59 women were nullipara. Among the pregnancy with SCH group, 87 women were nullipara and 113 women were nullipara. Serum TSH level was 4.44 ± 0.11 in 1st trimester, 4.74 ± 0.19 in 2nd trimester, 5.45 ± 0.17 in 3rd trimester. Serum free T4 level was 8.29 ± 0.13 in 1st trimester, 6.65 ± 0.15 in 2nd trimester, 6.67 ± 0.34 in 3rd trimester. In pregnancy with SCH group gestational hypertension, miscarriage, placental abruption and premature rupture of membranes (PROM) were significantly higher (p&lt;0.001). Antepartum hemorrhage (APH), preterm delivery and Caesarian deliveries were also higher in this group (p&lt;0.05). Among the neonatal outcomes, low birth weight and intrauterine growth restriction (IUGR) babies were more born in pregnancy with SCH group. Anti TPO antibody titer was significantly higher in pregnant women with SCH. Conclusion: Subclinical hypothyroidism (SCH) is associated with increased risk of gestational hypertension, premature rupture of membranes (PROM), abruptio placentae and fetuses have more risk of IUGR and LBW. Therefore, routine maternal thyroid function test should be done to protect from adverse maternal and fetal outcome.

Correlation of subclinical hypothyroidism with sarcopenia and its components in the Chinese older adults.

To identify the correlation of thyroid function and subclinical hypothyroidism (SCH) with sarcopenia and its components in the older Chinese adults. Older adults were recruited and divided into SCH group and non-SCH group. Free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescence. Appendicular skeletal muscle mass (ASM) was measured, and skeletal muscle index (SMI) was further calculated. Grip strength was measured. Physical performance was graded by the Short Physical Performance Battery (SPPB) scores of the gait speed test, chair stand test and balance test. Of the 240 older adults included, 48 (20.00%) presented with SCH. The prevalence of sarcopenia in SCH group was higher than that in non-SCH group (33.33% v.s. 18.75%). Grip strength was significantly lower in patients with SCH than those without sarcopenia. In terms of physical performance, 6-meter gait speed and SPPB score were lower in subjects with SCH than those without SCH, while 5 sit-to-stand movements was longer score in subjects with SCH than those without SCH. SCH was significantly correlated with sarcopenia, while FT3, FT4, and TSH levels were not. SCH was significantly correlated with low muscle strength and low muscle mass, but not with low physical performance. FT3 level was positively correlated with grip strength and SMI. TSH level was negatively correlated with grip strength, 6-meter gait speed, and SPPB score, but positively correlated with the time of 5 sit-to-stand movements. SCH is a risk factor for sarcopenia in the older adults and correlated with low muscle strength and low muscle mass, but not with low physical performance. FT3, FT4 and TSH levels are associated with sarcopenia components, but not with sarcopenia.

Association of vitamin D with triglyceride-glucose index and cardiometabolic risk factors in subclinical hypothyroidism

BackgroundThe present study aimed to explore the association of vitamin D with triglyceride-glucose (TyG) index and cardiometabolic risk factors in subclinical hypothyroidism (SCH). MethodsWe recruited 75 individuals diagnosed with SCH and 75 healthy controls of both genders aged 20 to 65 years. Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and 25-hydroxyvitamin D [25(OH)D] were measured using chemiluminescent immunoassay. Fasting plasma glucose and lipid profile were analyzed by standard methods. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. ResultsThere were significant decreases in 25(OH)D levels and changes in cardiometabolic risk factors among individuals with SCH compared to healthy controls. Additionally, there was a significant increase in the TyG index among the SCH group. Correlation and regression analysis revealed that 25(OH)D was significantly and negatively associated with TyG index, diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C). However, it was positively associated with high-density lipoprotein cholesterol (HDL-C). ConclusionPresent study shows that SCH patients have lower vitamin D levels and higher TyG index, increasing cardiovascular disease risk. Screening and managing vitamin D deficiency is crucial in these subjects. In addition, TyG index could be used as an indicator for identifying vitamin D deficiency.

Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff.

Subclinical hypothyroidism (SCH) is defined by elevated thyrotropin (TSH) and normal level of thyroxine (T4). The definition of SCH and the cutoff for TSH normality in pregnancy are debated. In the present study, we assess offspring perinatal outcome, anthropometrics and early development in relation to different TSH levels. An observational study with 77 singleton-pregnant women included by thyroid screening before a planned cesarean section. Two TSH-cutoffs (3.0 and 3.7 mIU/L) defined euthyroid and SCH groups, and were applied to evaluate offspring anthropometrics, complication rates (maternal blood loss, Apgar-score, cord arterial-pH, admission to neonatal intensive care unit, perinatal hypoglycemia) and offspring development. Development was evaluated by Bayley-III test in a subsample at age 6months (n=27) and 15months (n=22). Prevalence of SCH was 31.2 % at TSH-cutoff 3.0 mIU/L, and 16.9 % at TSH-cutoff 3.7 mIU/L. No differences in complications and anthropometrics were observed. In Bayley-III tests, cognitive score was decreased at 6 months (p=0.012) and at 15months (p=0.056) by applying TSH-cutoff 3.0 mIU/L. At cutoff 3.7 mIU/L, motor score was decreased at 15months (p=0.020). Male offspring had significantly lower cognitive scores at age 6 and 15months (TSH-cutoff 3.0 mIU/L), and motor scores at age 15months (TSH-cutoff 3.7 mIU/L). The importance of the definition of thyroid normality in pregnancy is underlined. This study suggests that a gender-effect might be present in maternal thyroid disease, and that developmental differences exist if TSH-cutoff is low. Further research is needed.

Association of Subclinical Thyroid Dysfunction with Cognitive Impairment in Rats: The Role of Autophagy.

We investigated the effect of subclinical hyperthyroidism and subclinical hypothyroidism on cognitive function in rats and the role of autophagy in this process. Forty Wistar rats were randomized into normal control (NC), hyperthyroidism (Hyper), hypothyroidism (Hypo), subclinical hyperthyroidism (sHyper), and subclinical hypothyroidism (sHypo) groups. Cognitive function (spatial learning and memory) was tested by the Morris water maze test. Hippocampal histopathology was analyzed by H&E staining, and expression levels of caspase-3 in hippocampal CA1 neurons were measured. In addition, immunoblot analysis was performed to detect hippocampal autophagy-related proteins. Escape latency from day 1 to day 4 was significantly longer in the Hypo, Hyper, and sHyper groups than in the NC group (P < 0.01). In addition, the number of rats crossing the virtual platform was significantly lower in the Hypo, Hyper, and sHyper groups than in the NC group (P < 0.01). Compared with the NC group, all four groups had significantly lower residence time in the target quadrant (P < 0.05). Beclin-1 and LC3-II protein expression in hippocampal tissues was significantly higher in the Hyper and sHyper groups than in the NC group (P < 0.01). Beclin-1 and LC3-II protein expression in hippocampal tissues did not significantly differ between the sHypo group and NC group (P > 0.05). Subclinical thyroid dysfunction in rats might lead to cognitive impairment. Subclinical hyperthyroidism might be associated with excessive activation of autophagy and hippocampal neuron damage and necrosis.

Impact of levothyroxine therapy for maternal subclinical and overt hypothyroidism on early child neurodevelopment: A prospective cohort study.

Treatment indication of maternal subclinical hypothyroidism (SCH) is undetermined, despite the wide administration of levothyroxine for maternal overt hypothyroidism (OH). This study aimed to evaluate the therapeutic effect of levothyroxine for maternal SCH and OH in real-world practice, with a focus on early child neurodevelopment. Prospective cohort study. Pregnant women diagnosed with SCH at the first antenatal visit were enroled and compared to those diagnosed with OH. Thyroid follow-ups were conducted during pregnancy. Early child neurodevelopment was assessed using the Gesell Development Diagnosis Scale (GDDS) at 1, 3, 6, 12and 24 months of age. From January 2012 to December 2013, a total of 442 pregnant women were included in final analysis, among whom 194 and 248 were assigned to the SCH and OH groups, respectively. The percentage of levothyroxine therapy at the first antenatal visit was significantly lower in the SCH group than that in the OH group (91.24% vs. 97.58%, p < .01), with a similar treatment rate at delivery (99.4% vs. 100%, p > .05). Notably, GDDS scores were lower in the SCH group than those in the OH group at 6 months to 2 years of age, which was confirmed by subgroup analyses and sensitivity analyses. Children born with maternal SCH demonstrated slightly lower neuropsychological scores at 6 months to 2 years of age compared to those with maternal OH in the clinical practice. The therapeutic effect of maternal SCH on the child neurodevelopment requires further exploration.

Analysis of Subclinical Thyroid Dysfunction and Metabolic Abnormality in 28568 Healthy People.

We analyzed the detection rates of metabolic syndrome (MetS) and subclinical thyroid dysfunction, including subclinical hyperthyroidism (SCHyper) and subclinical hypothyroidism (SCH), in healthy people, as well as their relationship. Clinical data were collected from 28,568 healthy individuals who underwent physical examinations. The detection rates of SCHyper, SCH, and MetS, as well as in different genders and ages, were analyzed. The detection rate of SCHyper and SCH in females was significantly higher than that in males (P < 0.001), but that of MetS in males was significantly higher than that in females (P < 0.001). In each age group, the detection rate of SCH in females was higher than that in males (P < 0.001). The detection rate of SCH was significantly different in different age groups (P < 0.001). The detection rates of hyperlipidemia (P < 0.001), obesity (P = 0.004), hypertension (P = 0.009), and hyperglycemia (P < 0.001) in the female SCH group were significantly higher than those in the normal group. The detection rates of hyperlipidemia (P = 0.006), obesity (P = 0.04), and hypertension (P = 0.04) in the male SCH group were higher than those in the normal group. The males with SCHyper were more prone to hyperlipidemia (P = 0.02) and obesity (P = 0.03). In addition, the female SCHyper group was not significantly different from the normal group (P > 0.05). Conclusively, the detection rate of SCHyper and SCH in females is higher than that in males, which increases with age. Attention should be paid to subclinical thyroid dysfunction in elderly people, especially females. Early individualized screening and early intervention should be carried out for people with abnormal metabolism.

The relationship between serum superoxide dismutase and thyroid function in obese patients after Laparoscopic sleeve gastrectomy

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity (n = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n = 112) and high levels of SOD (HSOD, n = 107) according to the median value of SOD levels (183 U/mL). SOD and thyroid hormones were measured and compared at baseline, 3, 6, and 12 months after LSG. The HSOD group had lower body mass index (BMI), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) than the NSOD group (p < 0.001, p = 0.031, p < 0.001, respectively). However, they had higher free triiodothyronine (FT3) and free thyroxine (FT4) (p = 0.019 and p = 0.017, respectively). SOD was significantly negatively associated with TSH and positively associated with FT4. Of all the patients, 22.31% (NSOD: 66.67%; HSOD: 33.33%) had subclinical hypothyroidism (SH), and there were lower SOD levels in the SH group. Preoperative SOD was a protective factor for SH. After LSG, SOD and FT4 levels were increased at 12 months after LSG, however, TSH, FT3, total triiodothyronine (TT3) and TT4 levels decreased compared to the preoperative levels at 3, 6, and 12 months in the SH group. Postoperative changes in FT4 and TT4 levels correlated with changes in SOD levels. SOD, which is correlated with thyroid hormones, protects against SH in patients with obesity. The improvement in thyroid function with SH after LSG may be related to increased SOD levels.

EVALUATION OF THYROID PROFILE AND ITS PROGNOSTIC VALUE IN PATIENTS OF ACUTE CORONARY SYNDROME

Objective: The objective of the study is to study the association of thyroid dysfunction with acute coronary syndrome (ACS), its complications and duration of hospital stay. Methods: This prospective comparative study was done on 100 patients divided equally into ACS patients with control (normal thyroid function) and ACS patients with thyroid dysfunction admitted in a tertiary care center, Udaipur, Rajasthan with ACS during the period of February 2021–July 2022. We studied the prevalence, prognostic factor of thyroid hormone in these patients. Results: The mean ejection fraction of the control group was 51.16±11.72%, of hypothyroid group was 49.00±13.55% and of hyperthyroid group was 51.12±13.78%. 29 cases of cardiac failures, 38 cases of arrhythmias, and 32 cases of major adverse cardiac events were observed. 56% of patients required thrombolysis, out of which 67.86% were from the subclinical hypothyroid group. The mean hospital stay in control group was 4.53±1.55, in hypothyroid group was 5.27±1.84 and in hyperthyroid group was 7.00±1.92.18% mortality. Conclusion: Patients with acute myocardial infarction, initially develop alteration in thyroid hormone levels, which is possibly a compensatory mechanism to reduce the metabolic demand of the heart, by reducing myocardium contraction and cardiac output but may cause cardiac failure and higher rates of cardiovascular complications like arrhythmias and death in some of the patients. Thyroid dysfunctions in patients with ACS may also need a longer duration of intensive care and close monitoring during follow-up.

Expressions of mitochondria-related genes in pregnant women with subclinical hypothyroidism, and expressions of miRNAs in maternal and cord blood

BackgroundSubclinical hypothyroidism in pregnancy and definition by upper thyrotropin (TSH) cutoff are controversial. As mitochondria are influenced by thyroid hormones, the purpose in this study was to measure expression of mitochondria-related genes in euthyroid and subclinical hypothyroid pregnant women to obtain more knowledge of potential metabolic consequences of maternal subclinical hypothyroidism. In addition, we wished to test if applied TSH-cutoff significantly changed our results of expressed gene-levels. Moreover, we aimed to identify potential microRNA-biomarkers for subclinical hypothyroidism – markers that could be traced to offspring as well.MethodsFrom a cohort of at-term pregnant women undergoing planned cesarean section, 77 women had expression levels of the mitochondria-related genes Peroxisome Proliferator-activated Receptor-γ coactivator-1β (PGC-1β), mitochondrial Transcription Factor A (TFAM), Superoxide Dismutase 2 (SOD2) and Nuclear Respiratory Factor 2 (NRF-2) determined by qPCR from blood sampled in prior to delivery. Two TSH-cutoff levels defining subclinical hypothyroidism (> 3.0 and > 3.7 mIU/L) were applied for the procession of results, generating two data analyses of the same cohort. In 22 pairwise maternal-cord samples (subclinical hypothyroid/euthyroid-rate 0.5, TSH-cutoff > 3.0 mIU/L), microRNA-expressions (miRNA) were analyzed.ResultsAll gene expressions were lower in the subclinical hypothyroid group regardless of applied TSH-cutoff, but insignificant except for PGC-1β at TSH cutoff > 3.0 mIU/L. Two miRNAs (hsa-let-7d-3p and hsa-miR-345-5p) were upregulated in blood from women and offspring (cord blood) with subclinical hypothyroidism.ConclusionsA trend towards decreased mitochondrial gene expressions in subclinical hypothyroidism were demonstrated. The miRNAs hsa-let-7d-3p and hsa-miR-345-5p might be potential markers of maternal subclinical hypothyroidism. However, larger studies are needed to verify the findings.

Maternal and Neonatal Outcomes of Sub-clinical Hypothyroidism Treated With Levothyroxine in Pregnancy: A Retrospective Cohort Study.

The effect of sub-clinical hypothyroidism (SCH) in pregnancy has been controversial. Furthermore, the impact of levothyroxine replacement on improving outcomes in pregnant women with SCH is unknown. This study aimed to assess the maternal and neonatal outcomes of pregnant women with SCH who were treated with levothyroxine replacement. This retrospective chart review was conducted at a tertiary hospital in Iran between 2020 and 2022. All pregnant women who had given birth during the study period were recruited. Those who did not have thyroid function test results within 10-12 weeks, as well as those with SCH who did not have levothyroxine replacement, were excluded. The subjects were divided into two groups based on the 2017 American Thyroid Association (ATA) criteria: non-SCH (TSH values 0.27-2.5 mIU/L) and SCH (TSH values more than 4.0 mIU/L). The demographic, obstetric, maternal, and neonatal outcomes of both groups were compared. The Chi-square test was used to compare the categorical variables. Binary logistic regression was used to assess differences in categorical variables. With a frequency of 10.5%, 935 women out of 8888 were diagnosed with SCH. In terms of age, educational level, living residency, medical insurance, access to prenatal care, and smoking status, there were no differences between the two groups. In terms of gestational age, parity, onset of labor, history of infertility, hypertension, cardiovascular disease, anemia, and overt diabetes, there were no differences between the two groups; however, gestational diabetes was more common in those with SCH. Compared with the non-SCH group, the prevalence and risks of gestational diabetes [19.8 vs. 14.2, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.72-3.95] were significantly higher in the SCH group after controlling for confounding factors. There were no differences in neonatal outcomes between the two groups. Except for gestational diabetes, we found no significant adverse events in terms of maternal and neonatal outcomes among women with SCH who were treated with levothyroxine.

Serum IL-27 levels increase in subjects with hypothyroidism and are negatively correlated with the occurrence of nonalcoholic fatty liver disease.

The level of serum interleukin-27 (IL-27) was significantly decreased in the obesity group. After injection of IL-27, obese mice showed significant weight loss,reduced fat accumulation, improved insulin resistance and hepatic steatosis.IL-27 plays a key role in the regulation of metabolic processes, but there are scarce data on circulating IL-27 levels in hypothyroidism. The purpose of this study was to assess the serum levels of IL-27 in patients with hypothyroidism and its relationship with NAFLD. 185 participants were included in this cross-sectional survey. According to thyroid function, the subjects were classified into three groups: euthyroidism (n = 55), subclinical hypothyroidism (n = 53), and hypothyroidism (n = 77). Serum IL-27 concentrations were measured by ELISA. Serum IL27 levels were significantly higher in subclinical hypothyroidism and hypothyroidism groups than in the euthyroidism group. Serum IL27 levels had a negative correlation with HOMA-IR,FBG,TG, subcutaneous fat,and visceral fat, and had a positive correlation with HDL-C (P< 0.05). Furthermore, logistic regression analysis indicated that IL-27 levels, HOMA-IR, and visceral fat showed significant associations with NAFLD after complete adjustment (P< 0.05). ROC curves showed that theoptimal cut-off value of serum IL-27 for discriminating NAFLD was 95.87pg/mL. The area under the ROC curve was 77.3% (95% CI = 0.694-0.851, p < 0.001). Serum IL-27 levels demonstrated a compensatory increase in patients with subclinical hypothyroidism or hypothyroidism and showed an independent association with NAFLD. Circulating IL-27 levels could predict the occurrence of NAFLD in hypothyroidism. These results suggested that altering the circulating levels of IL-27 may be a potential therapeutic target for NAFLD.

Comparison of Frequency and Types of Anemia in Subclinical Hypothyroidism and Euthyroidism

Objective: To compare the frequency and types of anemia in subclinical hypothyroid and euthyroid patients. Study Design: Comparative cross sectional study. Place and Duration: Department of Medicine, PNS Shifa, Karachi Pakistan, from Jun 2019 to Dec 2019. Methodology: All patients who fulfilled the inclusion criteria and visited Medicine Department, PNS Shifa Karachi were included in the study. After ethical approval and informed written consent patients were divided into two groups, subclinical hypothyroidism group (149 patients) and euthyroid group (148 patients). Blood samples of all included patients were sent for hematocrit, mean cell volume and hemoglobin level to assess the outcome i-e anemia &amp; its different types. Results: A total of 297 patients were included in the study. Amongst the sub clinically hypothyroid patients, anemia wasnoted in 40 patients (26.9%), while in the euthyroid group, it was noted in 23 patients (15.5%). In the subclinical hypothyroidism group, the type of anemia was microcytic in 13 patients (8.7%), macrocytic in 7 patients (4.7%) and normocytic in 20 patients (13.4%); while in the euthyroid group, anemia was microcytic in 7 patients (4.7%), macrocytic in 4patients (2.7%) and normocytic in 12 patients (8.1%). Conclusion: The commonest type of anemia found in sub clinically hypothyroid patients is normocytic normochromic anemia.The frequency of anemia was 26.9% in the subclinical hypothyroid group and 15.5% in the euthyroid group.

Subclinical hypothyroidism increases insulin resistance in normoglycemic people.

To investigate the effect of simple subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM) combined with SCH on insulin resistance. A total of 622 people with newly diagnosed T2DM were selected as the study subjects, and 621 normoglycemic people were selected as control subjects. According to the diagnostic criteria of thyroid diseases, the subjects were divided into a normal thyroid function group and a subclinical hypothyroidism group. Both groups received a physical examination, and blood samples were collected. The measurement indexes included FPG, FINS, OGTT2hPG, OGTT2hINS, HbA1c, TC, TG, HDL-C, LDL-C, TSH, FT3 and FT4. HOMA-IR, HOMA-β, and TFQI (thyroid feedback quantile index) were calculated. There was no significant difference in age or sex distribution between the T2DM group and the normoglycemic group (P>0.05). The prevalence of thyroid dysfunction in the T2DM group was significantly higher than that in the normoglycemic group (16.39% vs. 11.27%, P<0.05), and among the different types of thyroid dysfunction, the prevalence of SCH was the highest at 14.95% (P<0.05). There was no significant difference in BMI, waist-hip ratio, blood lipid profile, HOMA-β, and HOMA-IR values between the T2DM with subclinical hypothyroidism group (T2DM+SCH+ group) and the normal thyroid function group (T2DM+SCH- group) (P>0.05). The BMI, waist-hip ratio and HOMA-IR values of the normoglycemic group with subclinical hypothyroidism (T2DM-SCH+ group) were significantly higher than those of the normoglycemic group with normal thyroid function (T2DM-SCH- group) (P<0.05), and there were no significant differences between the T2DM+SCH- and T2DM+SCH+ groups (P>0.05). HOMA-β values were significantly higher in the T2DM-SCH+ group than in the T2DM-SCH-, T2DM+SCH- and T2DM+SCH+ groups (P<0.05). As the TFQI value increased, the body weight, waist-hip ratio, diastolic blood pressure, FPG, OGTT2hPG and HbA1c values gradually increased in the T2DM group and normoglycemic group (P<0.05). HDL-C, FINS, OGTT2hINS and HOMA-β values gradually decreased (P<0.05). Subclinical hypothyroidism only increases insulin resistance in normoglycemic people. As the sensitivity of the central thyroid decreases, the risk of developing diabetes increases.

Alteration of Lipid Profile Between Subclinical Hypothyroidism and Well-Matched Controls: A Meta-Analysis.

In previous studies, subclinical hypothyroidism (SCH) has been associated with altered lipid profiles. However, since the discrepancy between these study results may reside in the great heterogeneity of the populations studied, this relationship is controversial. This study aimed to explore the changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) between subclinical hypothyroidism (SCH) and well-matched euthyroid (EU) groups. Multiple databases were searched for publications before December 1, 2021, including cross-sectional studies on the association between SCH and lipid profile matched by age, gender, and BMI. Twenty-five articles with 3347 participants were included for meta-analysis. The results showed that the TC, TG, and LDL-c levels of the SCH groups were higher than the EU groups (TC, SMD=0.49, 95% CI 0.27, 0.71, p<0.001) (TG, SMD=0.43, 95% CI 0.21, 0.64, p<0.05 ) (LDL-c, SMD=0.75, 95% CI 0.46, 1.03, p<0.001 ). The HDL-c levels of the SCH group were lower than the control group (SMD=-0.53, 95% CI -0.81, -0.25, p<0.05). SCH has a larger impact on LDL-c than the other three indicators. After subgroup analyses, there was a larger impact on lipid alteration in the subgroup of TSH>10 μIU/ml, especially on LDL-c. This study found that SCH was associated with altered lipid profiles. Appropriate clinical treatment may be needed to prevent dyslipidemia and related diseases.