The long-term prognostic implications of free triiodothyronine to free thyroxine ratio in patients with obstructive sleep apnea and acute coronary syndrome.

Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain. Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of ≥15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015). Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA.

Thyroid functions and insulin resistance in pregnant Sudanese women.

BACKGROUND: The thyroid function test (free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH]) is one of the key determinant of glucose homeostasis by regulating the balance of insulin. Thyroid dysfunction alters glucose metabolism, leading to insulin resistance (IR). This study aimed to assess the association between thyroid function and IR in pregnant Sudanese women. METHOD: A cross-sectional study was conducted in Saad Abuelela Hospital, Khartoum-Sudan, from January to April 2021. Obstetric/sociodemographic characteristics were gathered through questionnaires. Serum TSH, FT3, FT4, fasting plasma glucose (FPG), and fasting insulin levels were measured and evaluated, and IR was estimated using the homeostatic model assessment for insulin resistance (HOMA-IR) equation. RESULTS: In total, the study included 127 pregnant women with a median age of 27.0 years (interquartile range [IQR] 23.0‒31.2) and a median gestational (IQR) age of 25.0 (IQR 25.0‒27.0) weeks. The medians (IQRs) of the TSH, FT3, and FT4 were 1.600 (1.162‒2.092) IU/ml, 2.020(1.772‒2.240) nmol/l, and 10.70 (9.60‒11.90) pmol/l, respectively. The median (IQR) of the FPG and fasting blood insulin level was [69.0 (62.00‒78.00) mg/dl] and [5.68(2.99‒11.66) IU/ml], respectively. The median (IQR) of the HOMA-IR level was 0.9407 (0.4356‒2.1410). There was a positive correlation between HOMA -IR and FT3 levels (r = 0.375; P < 0.001) and a negative correlation with FT4 levels (r= -0.312; P < 0.001). Also, a significant positive correlation was found between fasting insulin levels and FT3 levels (r = 0.438; P < 0.001) and a negative correlation with FT4 levels (r= -0.305; P < 0.001). CONCLUSIONS: This study indicated that FT3 has positive correlation with HOMA-IR, while FT4 has negative correlation among healthy pregnant women without a history of thyroid dysfunction. This may indicate screening of euthyroid pregnant women for thyroid dysfunction and IR. Further studies are needed.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is associated with thyroid hormones and thyroid hormone sensitivity indices: a cross-sectional study.

BACKGROUND: Lipids and thyroid hormones (TH) are closely interrelated. However, previous studies have not mentioned the linkage encompassing the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) alongside TH level, as well as sensitivity indices. METHODS: This cross-sectional study leverages expansive datasets from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. Weighted multivariate linear regression, smoothed curve fitting and sensitivity analyses were used to investigate the associations of the NHHR with the thyroid. Subgroup analyses and interaction tests were conducted to determine the robustness of the findings across diverse segments of the population, ensuring the consistency and generalizability of the observed associations. RESULTS: The NHHR was significantly positively correlated with free triiodothyronine (FT3) levels, thyroid-stimulating hormone (TSH) levels, the FT3 to FT4 ratio (FT3/FT4), and the quantile-based thyroid feedback index for FT3 (TFQIFT3) and negatively correlated with free thyroxin (FT4) levels [0.17(0.07-0.27), P = 0.001; 0.60 (0.03-1.17), P = 0.040; 0.06 (0.04-0.08), P < 0.0001; 0.23 (0.16-0.30), P < 0.0001; and -0.65 (-1.05--0.24), P = 0.002]. Smoothed curve fitting revealed nonlinear correlations of the NHHR with thyroid function and thyroid hormone sensitivity indices. In subgroup analyses, interaction tests, and smoothed curve fitting analyses, different populations presented largely consistent statistical differences. CONCLUSION: Among American adults, the NHHR was significantly positively correlated with FT3 levels, TSH levels, the FT3/FT4 and the TFQIFT3. Conversely, a negative association was noted between the NHHR and FT4 levels.

Establishment of reference intervals of thyroid-related hormones for adults with normal liver function in Zhejiang Province by indirect method.

Objective: Thyroid disorders are prevalently diagnosed yet face significant challenges in their accurate identification in China. Predominantly, the reference intervals (RIs) currently in use across Chinese medical facilities derive from company-provided data, lacking stringent scientific validation. This practice underscores the urgent necessity for establishing tailored RIs for thyroid-related hormones, specifically tailored to the coastal area populations. Such refined RIs are imperative for empowering clinicians with the precise tools needed for the accurate diagnosis of both overt and subclinical thyroid conditions. Methods: This investigation analyzed the medical histories of 6021 euthyroid individuals mainly from East coastal area of China between June 2019 and December 2020. The cohort comprised residents of coastal areas, focusing on extracting insights into the regional specificity of thyroid hormone levels. A thorough examination protocol was implemented, encompassing inquiries into thyroid health history, ultrasound screenings, palpations during thyroid surgery, detections of thyroid antibodies, and reviews of medication histories. Adherence to the CLSI C28-A3 guidelines facilitated the derivation of RIs for thyroid-related hormones, subsequently juxtaposed against those provided by commercial entities. Results: The study delineated the following gender- and age-specific RIs for Thyroid-Stimulating Hormone (TSH): for males under 50 years, 0.57-3.37; males over 50 years, 0.51-4.03; females under 50 years, 0.53-3.91; and females over 50 years, 0.63-4.31. Further analysis revealed the RIs for Free Thyroxine (FT4), Free Triiodothyronine (FT3), Total Thyroxine (TT4), and Total Triiodothyronine (TT3) amongst males and females, with notable distinctions observed between the two genders and across age brackets. These findings are in stark contrast to the standardized intervals provided by manufacturers, particularly highlighting differences in TT3 and FT3 levels between genders and a tendency for TSH levels to increase with age. Conclusion: This research successfully establishes refined RIs for thyroid-related hormones within the Chinese coastal area populations, taking into account critical demographic factors such as gender and age. These tailored RIs are anticipated to significantly enhance the diagnostic accuracy for thyroid diseases, addressing the previously noted discrepancies with manufacturer-provided data and underscoring the importance of regionally and demographically adjusted reference intervals in clinical practice.

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

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

Effects of Melatonin and 3,5,3'-Triiodothyronine on the Development of Rat Granulosa Cells.

Melatonin, as an endocrine neurotransmitter, can promote the development of the ovary. Meanwhile, it also has protective effect on the ovary as an antioxidant. Thyroid hormone (TH) is essential for normal human reproductive function. Many studies have shown that 3,5,3'-triiodothyronine (T3) regulates the development of ovarian granulosa cells. However, little is known about the specific mechanisms by which melatonin combines with T3 to regulate granulosa cell development. The aim of present study was to investigate the effects and the possible mechanisms of melatonin and T3 on ovarian granulosa cell development. In the present study, cell development and apoptosis were detected by CCK8, EdU and TUNEL, respectively. The levels of related proteins were analyzed by Western blotting. The results showed that oxidative stress (OS) and reactive oxygen species (ROS) were induced by H2O2 in granulosa cells, and cell apoptosis was also increased accompanied with the decreased cellular proliferation and viability. Melatonin protects granulosa cells from H2O2-induced apoptosis and OS by downregulating ROS levels, especially in the presence of T3. Co-treatment of cell with melatonin and T3 also promotes the expression of GRP78 and AMH, while inhibiting CHOP, Caspase-3, and P16. It was demonstrated that melatonin alone or in combination with T3 had positive effect on the development of granulosa cells. In addition, the AMPK/SIRT1 signaling pathway is involved in the process of melatonin/T3 promoting granulosa cell development.

Triiodothyronine (T3) promotes browning of white adipose through inhibition of the PI3K/AKT signalling pathway.

Obesity arises from an imbalance between energy consumption and energy expenditure, and thyroid hormone levels serve as a determinant of energy expenditure. We conducted experiments at the animal and cellular levels and combined those findings with clinical data to elucidate the role of triiodothyronine (T3) in facilitating the browning of white adipose tissue (WAT) and its underlying mechanism. The results showed (i) the impaired metabolic function of local WAT and the compensatory elevation of systemic thermogenesis in obesity; (ii) T3 treatment of white adipocytes in vitro and local WAT in vivo induced a shift towards a morphologically "brown" phenotype, accompanied by upregulation of mRNA and protein expression of browning-related and mitochondrial function markers, which suggest that T3 intervention promotes the browning of WAT; and (iii) the aforementioned processes could be modulated through inhibition of the PI3K/AKT signalling pathway; however, whether T3 affects the PI3K/AKT signalling pathway by affecting insulin signalling remains to be studied and clarified. The results of our study indicate that T3 treatment promotes browning of WAT through inhibition of the PI3K/AKT signalling pathway; these findings offer novel perspectives regarding the potential of localised therapies for addressing WAT volume in individuals with obesity.

The relation between FT3 and long-term fatigue in patients with COVID-19.

Background: Under the current pandemic of Corona Virus Disease 2019 (COVID-19), The relationship between fatigue and COVID-19 has been found. Infection with COVID-19 is associated with fatigue long after the acute phase of COVID-19. Understanding the association of thyroid hormones levels with post-COVID condition, such as fatigue, is necessary to improve quality of life. Methods: This population-based cohort study was conducted in Dalian, China, from December 2022, to March 2023, using a Yidu Core platform in the First Affiliated Hospital of Dalian Medical University, that integrates medical records, laboratory tests, and all diagnosis and treatment information based on patients in hospital. Eligible individuals were 40 patients with COVID-19, Divided them into fatigue group and non-fatigue group following up by telephone using the FS-14 scale after 6 months. The primary outcomes were the diagnoses of fatigue. The association between thyroid hormones levels and post-COVID condition, such as fatigue, was assessed using logistic regression analysis. Results: Compared with the non-fatigue group, the FT3 level in fatigue group was lower (p<0.05). FT3 was negatively correlated with fatigue after 6 months (OR 0.257, p<0.05). After adjusting for confounding factors such as age and gender, low FT3 was a risk factor for fatigue in patients with COVID-19, (OR 0.225, p<0.05). And the FT3 is less than 2.47 mol/L, it is the best critical value for predicting long-term fatigue, with a sensitivity of 92.3% and a specificity of 48.1%. Conclusions: Most people still have fatigue 6 months after COVID-19 infection. FT3 serves as the important index to predict fatigue in patients with COVID-19. it should be closely monitored during infection.

Psychotic symptoms in Chinese adolescent patients with major depressive disorder: prevalence and related endocrine clinical factors.

OBJECTIVE: Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. METHODS: In total, 601 patients (aged 12-18) with MDD were recruited. The Patient Health Questionnaire - 9 items (PHQ - 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. RESULTS: The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05). CONCLUSIONS: PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention.

The association between depression and thyroid function.

Background: Emerging evidence indicated that depression is currently one of the most burdensome diseases worldwide, and it can lead to a variety of functional physical impairments. However, the studies estimated the association between depression and thyroid function remain sparse. We aimed to investigate the association between depression and thyroid function in the American population. Methods: A cross-sectional analysis was performed using the data from the National Health and Nutrition Examination Survey conducted from 2007 to 2012. In the 12,502 adults aged 20-80 years, weighted linear regression models and multiple logistic regression models were applied to evaluate the association between depression and thyroid function indicators. The thyroid indicators investigated were mainly free thyroxine (FT4), total T4 (TT4), free triiodothyronine (FT3), total T3 (TT3), thyroid-stimulating hormone (TSH), and antithyroperoxidase antibody (TPOAb), thyroglobulin (Tg) and antithyroglobulin antibody (TgAb). Results: The final results were reached after adjusting for various confounding factors. In the stratification analysis of subgroups divided by age, depression was significantly negatively correlated with FT4, FT3, and TT3 in both younger adults (p = 0.00122, p < 0.00001, and p = 0.00003) and older adults (p = 0.00001, p = 0.00004, and p < 0.00001). In contrast, depression was significantly negatively correlated with TT4 and Tg in older adults (p = 0.00054, p = 0.00695) and positively correlated in younger adults (p = 0.01352, p < 0.00001). The subgroup analysis by gender revealed that depression was significantly negatively correlated with FT4, FT3, and TT3 in both adult males (p = 0.0164, p = 0.0204, and p = 0.0050) and adult females (p ≤ 0.0001, p < 0.0001, and p < 0.0001), which was more prominent in females. The positive correlation between depression symptoms and TPOAb was only found in adult females (p = 0.0282) and younger adults (p = 0.00488). Conclusion: This study confirmed a significant correlation between depressive and thyroid function and it varied among different genders or age. In the future, more prospective studies are needed to reveal these findings and confirm a causal relationship between them.