Association between Subclinical Hypothyroidism and Adverse Pregnancy Outcomes in Assisted Reproduction Technology Singleton Pregnancies: A Retrospective Study.

Background/Objectives: Women with subclinical hypothyroidism (SCH) were reported to be at an increased perinatal risk. We aimed to investigate the relationship between SCH and perinatal outcomes in singleton pregnancies resulting from assisted reproduction technology (ART). Methods: We retrospectively examined the perinatal outcomes of ART singleton pregnancies in women who underwent thyroid function screening before conception and delivered at our hospital from January 2020 to July 2023. We defined SCH as thyroid-stimulating hormone (TSH) levels > 2.5 mU/L and normal free T4 levels. The patients were categorized into three groups: normal thyroid function (group A), SCH without levothyroxine therapy (group B), and SCH with levothyroxine therapy (group C). The risks of preterm birth, preeclampsia, fetal growth restriction, manual placental removal, and blood loss at delivery were compared among the three groups. Results: Out of the 650 ART singleton deliveries, 581 were assigned to group A, 34 to group B, and 35 to group C. The preterm birth rate at <34 weeks was significantly higher in group B and significantly lower in group C than in group A. The rate of preterm delivery at <34 weeks increased in correlation with TSH levels. Levothyroxine therapy was the significant preventive factor for preterm birth at <34 weeks. Conclusions: The preterm birth rate before 34 weeks was significantly higher in the SCH group. Levothyroxine therapy is a significant protective factor against preterm birth before 34 weeks. Universal screening for thyroid function and appropriate hormone therapy in pregnant women may help reduce perinatal risks, including preterm birth.

A Clinical Study of Thyroid Abnormalities and Autoantibodies in Patients Diagnosed With Anti-nuclear Antibody Positive Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

INTRODUCTION: Autoimmune connective tissue disorders (CTDs) are characterized by inflammation of the connective tissue structures and immune system aberrations, such as autoantibody production. This study investigates the prevalence and clinical significance of thyroid abnormalities in patients with anti-nuclear antibody (ANA)-positive autoimmune CTDs. METHODS: This prospective cross-sectional observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, from September 2022 to June 2024. Eighty patients diagnosed with ANA-positive CTDs were included. Comprehensive histories were collected from them and clinical examinations and routine investigations were performed. Blood samples were collected for thyroid function tests and autoantibody tests. Thyroid ultrasound investigations were also performed. Ethical approval and informed consent were obtained. RESULTS: The study revealed a significant prevalence of thyroid dysfunction among participants, with 39 (48.75%) exhibiting some form of thyroid abnormality. Subclinical hypothyroidism was the most common condition in 18 (22.50%) participants, predominantly affecting females. Thyroid autoantibodies were present in 32 (40%) participants, with thyroid peroxidase antibodies (anti-TPO Ab) being the most common seen in 17 (21.25%) participants. Systemic lupus erythematosus (SLE) was the most prevalent CTD among participants, seen in 44 (55%) participants, followed by Sjogren's syndrome (SS) seen in 19 (23.75%) participants. CONCLUSION: The study underscores the necessity of routine thyroid function screening in patients with ANA-positive CTDs to facilitate early detection and management of thyroid abnormalities, thereby preventing progression to overt hypothyroidism or hyperthyroidism. The findings highlight the significant association between thyroid dysfunction and autoimmune CTDs, advocating for a holistic approach to patient care.

A Cross-Sectional Study on the Prevalence of Subclinical Hypothyroidism in Metabolic Syndrome Patients at a Tertiary Care Hospital.

BACKGROUND AND OBJECTIVE: Metabolic syndrome (MetS) is defined as a "constellation" of cardiometabolic risk factors, characterized by hypertension, atherogenic dyslipidemia, hyperglycemia, prothrombotic and proinflammatory conditions which, jointly, increase the risk of suffering cardiovascular diseases (CVD) and type 2 diabetes mellitus. Thyroid dysfunction is also believed to affect parameters such as high-density lipoprotein (HDL) cholesterol, triglycerides, plasma glucose, and blood pressure, in turn increasing the risk of CVD. Subclinical hypothyroidism (SCH), which independently raises the risk of CVDs and their associated complications, is more frequently detected in patients with MetS compared to the general population. When both conditions coexist, the risk of CVD and its complications is significantly heightened. The objective of the study was to find out the prevalence of SCH in patients with MetS. METHODS: A prospective cross-sectional study was conducted in the Department of General Medicine, New Civil Hospital, Surat, Gujarat, India. Eighty patients who fulfilled the criteria for MetS by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), were taken into the study. A detailed history, anthropometric measurements, blood pressure, fasting blood glucose, lipid profile, and thyroid profile (Free T3, Free T4, and serum thyroid-stimulating hormone (TSH)) were undertaken. The thyroid profile was done by chemiluminescence immunoassay (CLIA) method. RESULTS: Out of 80 patients with MetS, 48 were female and 32 were male, with the overall mean age of the study population being 46.5±9.5 years. Among them, 23.7% of the population was found to be having thyroid dysfunction. Among the thyroid dysfunction, SCH was highly prevalent (18.8%), 3.8% patients had overt hypothyroidism and 1.3% patients had subclinical hyperthyroidism. There were no overt hyperthyroid patients in our study. HDL (mg/dl) and TSH (mIU/L) were significantly higher in the SCH group as compared to other types of hypothyroidism group (p-value < 0.05). DISCUSSION: There is a statistically significant prevalence of SCH (18.8%) in MetS patients. It is clear from the study that one-fifth of MetS patients or every fifth patient with MetS had SCH. Thus, looking proactively for SCH in MetS and treating it would prevent conversion to overt hypothyroidism and complications of MetS.

Associative Learning in Subclinical Hypothyroidism at Different Ranges of Thyroid Stimulating Hormone: A Cambridge Neuropsychological Test Automated Battery (CANTAB) Study of Visual Paired Association Learning Task.

BACKGROUND: Associative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer's disease (AD). PURPOSE: This study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4. METHODS: A total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB. RESULTS: PAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD. CONCLUSION: Our findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD.

Association of maternal mild hypothyroidism in the first and third trimesters with obstetric and perinatal outcomes: a prospective cohort study.

BACKGROUND: Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy. OBJECTIVE: To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes. STUDY DESIGN: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes. RESULTS: Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group. CONCLUSION: This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function.

Differences in Vitamin A Levels and Their Association with the Atherogenic Index of Plasma and Subclinical Hypothyroidism in Adults: A Cross-Sectional Analysis in China.

BACKGROUND: This study evaluates the association between vitamin A levels, AIP (the atherogenic index of plasma), and subclinical hypothyroidism. METHODS: A cross-sectional analysis was conducted involving a representative sample of 3530 Chinese adults. Linear and logistic regression models were utilized to evaluate the associations between AIP and subclinical hypothyroidism, stratified by vitamin A levels. These analyses were further differentiated by sex and age groups to identify any demographic-specific associations. RESULTS: In the vitamin A-sufficient group, an increase in AIP was associated with elevated total triiodothyronine (TT3) levels (ß = 0.26, 95%CI: 0.09, 0.41, p = 0.003). Conversely, in the group with severe vitamin A deficiency, higher AIP levels were linked to increased free triiodothyronine (fT3) and TT3 levels and decreased free thyroxine (fT4) levels (ß = 0.12, 0.03, and -0.29, respectively). Additionally, severe vitamin A deficiency increased the risk associated with AIP and subclinical hypothyroidism (OR = 1.66, 95%CI: 1.07, 2.58, p = 0.025). This risk was notably more pronounced in women and older adults, with odds ratios of 2.44 (95%CI: 1.55, 3.86, p < 0.001) and 2.14 (95%CI: 1.36, 3.38, p = 0.001), respectively. CONCLUSIONS: Vitamin A deficiency may increase the risk of the association between AIP and subclinical hypothyroidism, particularly among women and the elderly.

Impact of Subclinical Hypothyroidism on Lipid Profile in Jeddah: A Retrospective Cohort Study.

Background Patients with subclinical hypothyroidism (SCH) have a high serum concentration of thyroid-stimulating hormone (TSH), whereas their serum-free thyroxine concentrations are normal. Lipid metabolism is regulated in large part by thyroid hormones. It could be connected to a changed lipid profile. This study aimed to evaluate the relationship between SCH and alterations in the lipid profile. Methodology Data from 99 patients with SCH and 109 euthyroid cases were collected from King Abdulaziz Medical City, Jeddah, Saudi Arabia, from 2016 to 2022. Patients older than 18 years were included in the study. The groups were matched in terms of gender, age, and body mass index. SCH was defined as a TSH value of 4.5 to 10 mIU/L, and normal T4 as 5 to 18 µg/dL. Control cases had a normal TSH ranging from 0.45 to 4.5 mIU/L. The total serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels in both groups were examined and the results were recorded. Results In comparison to the control group, SCH patients had greater median glycated hemoglobin (HbA1C) (p = 0.001) and lower median vitamin D levels (p = 0.004) before therapy. Before therapy, SCH patients also showed considerably lower HDL levels and significantly higher LDL and TG levels (p < 0.001). Conclusions There is a substantial correlation between SCH and reduced HDL and vitamin D levels. It was linked to increased TG, LDL, and HbA1c levels. Only vitamin D and LDL were pathologically high. Treatment with levothyroxine raised total and LDL cholesterol levels. Future research should look into the affordability of treating SCH.

Levothyroxine Treatment of Subclinical Hypothyroidism and the Risk of Adverse Cardiovascular Events.

Importance: There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. Objectives: To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. Design: We conducted a population-based cohort study using a prevalent new-user design. Setting: The study utilized data from the United Kingdom Clinical Practice Research Datalink. Participants: We identified a base cohort of individuals aged ≥18 years with incident SCH defined as having at least two TSH levels between 5 and 10 mU/L within one year between 1998 and 2018. We matched 76,946 levothyroxine treated to 76,946 untreated individuals based on age, sex, calendar time, duration of SCH, and time-conditional propensity score. We compared individuals with SCH treated with levothyroxine with individuals with no treatment. Exposure: Levothyroxine treatment versus no treatment. Main Outcome Measures: The primary outcome, MACE, was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality. Results: The mean age of the study cohort was 62.8 years, and 76.5% were women. During a median follow-up time of 1.6 years (interquartile range: 0.5-4.2), the incidence rate for MACE among individuals treated with levothyroxine was 12.8 per 1000 person-years; confidence interval (CI): 12.2-13.3 and 13.9 per 1000 person-years; CI: 13.4-14.3 among nontreated individuals. Levothyroxine treatment was associated with a small decreased risk of MACE (hazard ratio: 0.88; CI: 0.83-0.93). Conclusions: Levothyroxine treatment of SCH was associated with a small decreased risk of MACE. However, given the observational nature of the study, residual confounding should be considered in the interpretation of this finding.

Evaluation of the etiology of subclinical hypothyroidism in children.

OBJECTIVES: Subclinical hypothyroidism (SH) is defined by normal free triiodothyronine (fT3) and free thyroxine (fT4) levels, elevated thyroid-stimulating hormone levels, and the absence of overt clinical signs of hypothyroidism. The natural course of SH is influenced by the underlying etiology. The purpose of this study was to evaluate the etiologic causes of SH. METHODS: A total of 135 patients aged 1-18 years, diagnosed with SH by at least two analytical measurements, were included in the study. The anthropometric measurements, demographic characteristics, and laboratory findings of the patients were determined. A comparison was conducted between patients with Hashimoto's thyroiditis and patients with non-autoimmune etiology. RESULTS: The median age was 9.7 (6.5) years, and 82 of the 135 patients were female. The most prevalent etiology was idiopathic, affecting 39 (28.9 %) patients. This was followed by obesity, which was identified in 21 (15.6 %) patients. Hashimoto's thyroiditis was the third most common cause, accounting for 18 (13.3 %) patients. In patients with Hashimoto's disease, fT4 levels were significantly lower, and the rate of initiation of LT4 treatment was higher than in patients with other etiologies. A heterozygous variation in the TSH receptor (TSHR) gene was detected in six patients. CONCLUSIONS: In our study, idiopathic cases were the most frequently identified in the etiology of SH. It is important to determine whether there is autoimmune thyroiditis. In cases of idiopathic SH, it is recommended to perform TSHR gene analysis, particularly in the presence of positive family history and newborn screening results. This approach will help elucidate the underlying etiology.

Diagnosis of Thyroid Nodules in Children and Adolescents with Subclinical Hypothyroidism and Their Outcomes after Early Thyroxine Treatment-A Longitudinal Study.

Pediatric thyroid nodules (TNs) present a higher malignancy rate compared to adults. We sought to diagnose the frequency and characteristics of TNs in children and adolescents with subclinical hypothyroidism (SH) and their outcomes after levothyroxine (LT4) therapy. A total of 256 children with TNs and SH were followed every semester from 2006 to 2018. All patients were treated with LT4. Clinical and radiologic findings, such as the size and texture of the nodules, were documented. Analysis included one-way ANOVA, Kruskal-Wallis, Chi-square, and Fisher's exact tests. After initial LT4 therapy, TNs disappeared in 85.5% and did not reappear throughout follow-up. In 14.5%, TNs remained the same or increased in size, but they decreased after subsequent LT4 administration with an increased dose. Thyroid disease family history (FHTD) was documented in 77.0%. In total, 64.5% developed a goiter, 46.0% exhibited thyroid heterogeneity on ultrasound, 23.4% had positive Anti-Tg, and 25.4% had positive anti-TPO autoantibodies. Our findings support the possible premise that early pharmacologic intervention with LT4 may be beneficial in children and adolescents with TNs and SH. The increased frequency of FHTD, goiter, thyroid heterogeneity, and Hashimoto in our patients emphasizes that thyroid ultrasounds may be warranted in children and adolescents with these characteristics in order to rule out the presence of TNs.

The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Metabolic syndrome and risk of subclinical hypothyroidism: a systematic review and meta-analysis.

Background: Subclinical hypothyroidism (SCH) is a common endocrine subclinical disorder, the main adverse consequences of which are the development of clinical hypothyroidism and the promotion of ischemic heart disease. Metabolic syndrome (MetS) is a collection of metabolic problems. The goal of this meta-analysis was to evaluate the relationship between MetS and SCH. Methods: Suitable publications were identified using PubMed, Embase, and the Cochrane Library. The meta-analysis included only studies in English that reported odds ratio (OR) data for MetS and SCH. Two researchers combined data using a random-effects model. OR and 95% confidence intervals (CIs) were used to present the results. Results: MetS was associated with an elevated risk of developing SCH (OR 2.56, 95% CI 1.44-4.55). However, the individual components of MetS were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH. Sensitivity analysis confirmed that our results were robust. Conclusions: This meta-analysis indicates that patients with MetS have an increased risk of SCH, while there is no significant association between the five individual components of MetS and the risk of SCH. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023454415.

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism.

INTRODUCTION: Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. MATERIAL AND METHODS: The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. RESULTS: There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). CONCLUSION: Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

Subclinical hypothyroidism and metabolic syndrome in psychiatric patients: A systematic literature review and meta-analysis.

OBJECTIVE: The systematic review evaluated the association of subclinical hypothyroidism (SCH) with metabolic syndrome (MetS) and specific MetS components in people with major psychiatric disorders. METHODS: A systematic review and meta-analysis was conducted to evaluate the association of SCH with MetS and its components in people with major psychiatric conditions. RESULTS: Five studies incorporating 24,158 participants met the inclusion criteria. All five studies comprised patients with depression and/or anxiety. Three studies incorporating 3365 participants were suitable for the meta-analysis. The pooled Odds Ratio (OR) of MetS was 3.46 (95% Confidence Interval/CI = 1.39-8.62) in major depressive disorder (MDD) and anxiety disorders patients with concurrent SCH compared to those without SCH. Meta-analysis showed a significant positive association between SCH and high body mass index (OR = 2.58, 95%CI = 1.33-5.01), high fasting plasma glucose (OR = 3.05, 95%CI = 1.79-5.18) and low high-density lipoprotein cholesterol (OR = 2.30, 95%CI = 1.82-2.92). CONCLUSIONS: These findings suggest a significant positive association between MetS and SCH in people with MDD and anxiety disorders. This review informed the clinical implications of MetS in MDD with comorbid SCH and the importance of early diagnosis and treatment for SCH and MetS in psychiatric patients.

Serum Vitamin B12 and Holotranscobalamin Levels in Subclinical Hypothyroid Patients in Relation to Thyroid-Stimulating Hormone (TSH) Levels and the Positivity of Anti-thyroid Peroxidase Antibodies: A Case-Control Study.

Background Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels, while thyroid hormones (free thyroxine (T4) and free triiodothyronine (T3)) remain within the reference ranges. Vitamin B12 (cobalamin) deficiency is common in patients with autoimmune disorders, including autoimmune hypothyroidism. The study was aimed at evaluating serum vitamin B12 levels and holotranscobalamin (HoloTC) levels in SCH patients and ascertaining their association with a risky level of TSH and the positivity of anti-thyroid peroxidase (anti-TPO) antibodies. Methodology A case-control study was conducted at Azadi Teaching Hospital, Duhok, a city in the Kurdistan region of Iraq, involving 153 participants, including 72 newly diagnosed SCH patients and 81 healthy controls. Serum levels of vitamin B12, HoloTC, TSH, free T4, free T3, and anti-TPO antibodies were measured based on different principles. Results The mean age of patients with SCH was 32.87±8.7 years, with predominantly females comprising 75% and 77.8% being less than 40 years of age. Moreover, the mean levels of serum TSH (6.96±2.68 µIU/L), anti-TPO antibodies (53.31±81.32 IU/ml), and HoloTC (41.93±19.42 pmol/l) were significantly higher in patients with SCH compared to healthy control participants (p < 0.05), whereas there was a non-significantly higher level of vitamin B12(320.72±98.42 pg/ml) among SCH patients compared to healthy control participants (p = 0.220). The mean levels of vitamin B12 (345.33±103.22 pg/ml) and HoloTC (40.14±18.16 pmol/l) were insignificantly lower in SCH patients with TSH levels more than 7 µIU/L (p > 0.05), as well as the mean levels of vitamin B12 (308.82±96.12 pg/ml) and HoloTC (41.14±19.29 pmol/l) insignificantly lower in SCH patients with positive anti-TPO antibodies (p > 0.05).  Conclusions This study highlights the potential association between SCH and altered vitamin B12 status, particularly evident in HoloTC levels. The presence of positive anti-TPO antibodies and the degree of elevation in TSH levels may exacerbate vitamin B12 deficiency in SCH patients.

Targeting the Manifestations of Subclinical and Overt Hypothyroidism Within the Hippocampus.

BACKGROUND: The past decade has witnessed a surge of articles describing the neurocognitive sequelae and associated structural and functional brain abnormalities of patients with overt hypothyroidism (OH) and subclinical hypothyroidism (SCH). Findings show effects primarily within the frontal lobes with usually worse outcomes for OH than SCH. Several recent studies have also indicated hypothyroid patients may have smaller hippocampi, a key structure for memory. CONTEXT: The JCEM paper by Zhang and colleagues applies 2 novel approaches for analyzing hippocampal structure and function. One uses an automated processing tool that segments the hippocampus into distinct subregions, and the other performs connectivity analysis to assess the relationships between specific hippocampal subregions and cortical areas. Relatively large samples of OH and SCH patients and healthy controls received a test of global cognitive functioning and underwent structural and functional magnetic resonance imaging. Results showed hypothyroid groups scored significantly below controls on the memory scale and also had smaller hippocampal volumes in selective subregions. Effects were stronger for SCH than OH groups, who also showed different patterns of interconnectivity between hippocampal subregions and specific frontal lobe areas. INTERPRETATION: To make sense of these findings, I explored the rodent and human literatures on thyroid hormone's role in hippocampal functioning and on hippocampal subfields and their purported functions and interconnections. Because current results suggest SCH may represent a distinct clinical entity with unique brain manifestations, I hypothesized 2 explanations for these findings, one involving transporter defects in the brain barriers and the other, differential neurodegeneration of the blood-brain barrier vascular unit.

Cerebral Venous Sinus Thrombosis Associated With Subclinical Hypothyroidism: A Case Report and Literature Review.

Thyroid dysfunction is a well-known cause of cerebral venous sinus thrombosis (CVST), but most reports have focused on CVST associated with hyperthyroidism, with only a few mentioning CVST associated with hypothyroidism. Subclinical hypothyroidism, characterized by thyroid hormone levels within reference values but elevated thyroid-stimulating hormone, can also cause CVST. Here, we present a case of CVST associated with subclinical hypothyroidism. A 48-year-old man with headache, nausea, and left-sided motor weakness was admitted to our hospital, with a history of economy-class syndrome. Magnetic resonance imaging revealed occlusion of the superior sagittal sinus, right transverse sinus, and right sigmoid sinus. Digital subtraction angiography (DSA) confirmed CVST from the right common carotid artery, revealing abnormal staining of the thyroid gland. The patient was serologically in a state of subclinical hypothyroidism. Consequently, the patient was diagnosed with CVST associated with subclinical hypothyroidism. Anticoagulation therapy was initiated shortly after admission. CVST gradually resolved, and the affected sinuses were recanalized. Paraplegia improved, and the patient was discharged home 19 days after admission with a modified Rankin scale of 1. Subclinical hypothyroidism can induce CVST, underscoring the importance of screening for thyroid function in CVST patients, even without apparent thyroid dysfunction symptoms. DSA findings are valuable for diagnosing thyroid disease.

Hypothyroidism and metabolic cardiovascular disease.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) on CV risk, CVD, and mortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH.

Effects of subclinical hypothyroidism in type II diabetes mellitus patients on biochemical, coagulation, and fibrinolysis status.

The aim of the currnet study to examine the effect of subclinical hypothyroidism (SCH) in diabetic patients on coagulation parameters. This retrospective case-control study involves 130 patients diagnosed with type 2 diabetes mellitus (T2DM), divided into 65 T2DM with newly diagnosed SCH and 65 euthyroid (EUT) T2DM patients without SCH. Fibrinogen (FIB) was significantly higher in SCH (508.2 ± 63.0 mg/dL) than EUT (428.1 ± 44.8 mg/dL). In the SCH patients, FIB correlated with several parameters, such as age (ß = 0.396), body mass index (ß = 0.578), glycated hemoglobin (ß = 0.281), and activated partial thromboplastin time (ß = 0.276). In conclusion SCH in DM patients appears to increase the magnitude of coagulopathy.

HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.