Search Results (541)

Ventricular remodeling occurring in heart failure (HF) involves structural disarray of the sarcolemma T-tubule (TT)–sarcoplasmic reticulum (SR) dyad junctions, thereby disrupting the close apposition of L-type Ca²⁺ channels (Ca_V1.2) with ryanodine receptors (RyR2) that trigger SR Ca²⁺ release and myofilament contraction. In a rat ischemic heart failure model expressing low thyroid hormone (TH) function, we used 3D stochastic optical reconstruction microscopy (STORM) to image RyR2 clusters with Ca_V1.2 channels, and the associated protein junctophilin-2 (Jph2). We tested whether treatment with T3, the biologically active form of TH, throughout progression of the disease would preserve T-tubule structure and dyadic ion channel organization. Confocal microscopy of isolated cardiomyocytes (CMs) stained with ANEPPS membrane dye showed significantly decreased TT density in diseased CMs while T3 treatment attenuated TT disorganization. 3D STORM images of dyadic ion channels labeled with fluorescent-tagged antibodies to RyR-Dylight550, Jph-CF647 and Ca_V1.2/IgG-Dylight488 were captured. A density-based algorithm defined RyR2 clusters, and a 400 nm spherical 3D volume of interest around each RyR2 cluster’s centroid determined the number of Ca_V1.2 and Jph2 localizations associated with each RyR2 cluster. Analysis revealed significant reduction in RyR2 cluster size and number with reduced co-localized Jph2 in failing CMs. T3 treatment increased RyR2 cluster numbers and cluster volumes albeit non-significantly, with increased co-clustering of Jph2. The number of Ca_V1.2 co-localized with RyR2 clusters trended lower in the failing CMs. These results support maintaining TH homeostasis in optimizing the nanoscale organization of Ca²⁺ ion channels in triggering Ca²⁺ release and myofibrillar contraction in patients with heart disease. Full article

Background: Post-thyroxine treatment of thyroid dysfunction remains a clinical concern, especially in Middle Eastern populations. Methods: This descriptive cross-sectional study was conducted in 2023 at King Fahad Hospital, Hufof, Kingdom of Saudi Arabia. Of the 237 patients treated with L-thyroxine (L-T4) for hypothyroidism, 163 patients, almost exclusively females (152 females, 11 males), met the inclusion criteria and were enrolled. Thyroid hormones, lipid profiles, and 25-hydroxyvitamin D (25OH-D) were measured using standard laboratory assays. Results: Only 57% of patients achieved euthyroid status following L-T4 treatment, while 12.3% developed post-thyroxine-treatment (PTT) hyperthyroidism, and 30.7% developed PTT hypothyroidism. Older age was significantly associated with dysthyroidism (p = 0.018), whereas obesity (p = 0.937) and vitamin D levels (p = 0.982) were not. Total cholesterol (TC) and LDLc positively correlated with TSH levels, while elevated triglycerides (TGs) were significantly associated with PTT hyperthyroidism. The two dysthyroid subgroups were comparable across all non-thyroid parameters, including age, BMI, 25(OH)D levels, and lipid fractions. However, free T4 was significantly higher in PTT hyperthyroidism (p < 0.001); free T3 showed a trend toward higher levels in PTT hyperthyroidism (p = 0.052); and TSH was significantly higher in PTT hypothyroidism (p < 0.001). Conclusions: The proportions of patients with PTT hypo- and hyperthyroidism are aligned with international observations. Furthermore, the age was significantly associated with dysthyroidism, and dyslipidemia is the most consistent biochemical correlate of suboptimal thyroid status; however, the associations of PTT dysthyroidism with hypovitaminosis D and BMI were not noticed in this setting. Full article

Background/Objectives: The present study estimated the potential therapeutic effects of Borassus flabellifer immature endosperm extract (BFE) on the metabolic disorders of diabetes and hypothyroidism using a mixed research design. Methods: Characterization of phytochemicals via GC-MS demonstrated a highly abundant list of bioactive compounds, and it encompassed phenolic derivatives, methylxanthines, fatty acids, and inositol-related compounds. Molecular docking indicated that the major phytoconstituents showed positive binding affinities to the most vital metabolism and endocrine receptors, namely, TRβ1, PPARγ, and AMP-activated protein kinase (AMPK). Notably, both compounds C1 and C2 were highly affined towards TRβ1 (−7.8 and −7.6 kcal/mol), which is attributed to interactions in the active site through hydrogen bonding and hydrophobic responses, which means that the identified compounds were found to have good predicted interactions with some metabolic- and thyroid-associated targets and could be used to form preliminary hypotheses for further mechanistic studies. The in vivo data showed that the disease-induced groups were marked by hyperglycemia, imbalance in thyroid hormones, and dyslipidemia, as well as liver, kidney, and heart dysfunction. BFE caused significant decreases in these changes, which were also observed through improvements in fasting blood glucose, T3, T4, and TSH; partial restoration of lipid profiles; and dampening of liver and kidney injury signalers. The cardiac risk indices were also reduced significantly after BFE administration. Positive changes in body weight gain, feed ratio, and metabolic ratio further reflected better physiological stability. Results: These findings were corroborated by histopathological analysis, which showed that the tissue architecture of the pancreas, liver, kidney, and heart had significantly recovered in the study. BFE still showed constant therapeutic activity even though the magnitude of response was attenuated when combined disease conditions were used. Conclusions: Comprehensively, the results indicate that BFE potentially plays a role in the amelioration of metabolic and endocrine abnormalities of diabetic and hypothyroid conditions. These observations should be regarded as hypothesis-generating, as further mechanistic and translational studies are needed to substantiate their biological relevance. Full article

Hypothyroidism is associated with metabolic, neurobehavioral, and reproductive alterations that may involve neuroendocrine regulatory peptides. Spexin, a neuropeptide implicated in energy homeostasis, has recently attracted attention for its possible role in thyroid and reproductive axis regulation. Therefore, this study aimed to investigate the effects of spexin on neurobehavioral responses and the tissue-specific expression of irisin and KISS-1 in the cerebral cortex and testis under hypothyroid conditions. Thirty-two male Wistar albino rats were randomly divided into four groups: Control, Hypothyroid (methimazole, 0.03% in drinking water for 35 days), Hypothyroid + Spexin (methimazole plus spexin, 25 µg/kg, intraperitoneally), and Spexin (25 µg/kg, intraperitoneally). Behavioral assessments were performed using the Open Field Test and Forced Swim Test. Serum thyroid hormone levels were analyzed, and brain and testis tissues were evaluated immunohistochemically for irisin and KISS-1 expression. Hypothyroid rats showed increased thyroid-stimulating hormone levels, decreased thyroxine concentrations. Spexin administration significantly reduced TSH levels and increased T4 concentrations. Spexin treatment reduced thigmotaxis compared to controls. No significant differences were found among groups in overall locomotor activity, time spent in the central zone, or FST parameters. Immunohistochemical analyses demonstrated reduced irisin and KISS-1 expression in hypothyroid rats, which was restored following spexin treatment. In conclusion, spexin exerted TSH-suppressive and T4-enhancing effects in experimental hypothyroidism. Its effects on irisin and KISS-1 expression suggest potential involvement in neuroendocrine and reproductive axis regulation. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated not only with tumor progression but also with profound metabolic and nutritional disturbances. Thyroid hormone homeostasis may reflect this systemic response; however, perioperative data in PDAC remain limited. We aimed to assess perioperative changes in thyroid-related parameters in patients with PDAC undergoing different types of surgical management and to explore their associations with nutritional, metabolic, and tumor-burden variables. Methods: We performed a retrospective single-center study including 101 patients with PDAC. Thyroid-related and metabolic laboratory parameters were assessed before surgery and again 4–6 weeks later. The analyzed variables included thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), the FT3/FT4 ratio, albumin, total protein, glucose, insulin, HbA1c, lipid parameters, and CA 19-9. Patients were analyzed according to resectional versus non-resectional treatment and according to four procedure types. The primary endpoint was perioperative change in the FT3/FT4 ratio. Results: At baseline, resectional patients had significantly higher FT3 and FT3/FT4 ratio values and lower FT4 and CA 19-9 levels than non-resectional patients. In the whole cohort, FT3 and the FT3/FT4 ratio decreased significantly after treatment, whereas TSH increased, and FT4 remained unchanged. These endocrine changes occurred in parallel with significant declines in albumin, total protein, glucose, insulin, HbA1c, and HDL cholesterol, together with an increase in triglyceride levels. Baseline FT3 and FT3/FT4 ratios correlated positively with albumin and total protein and negatively with CA 19-9. Although perioperative changes did not differ significantly between resectional and non-resectional groups except for triglycerides, significant procedure-dependent differences were observed across the four surgical categories for FT3, FT4, TSH, and the FT3/FT4 ratio; glucose; insulin; and triglycerides. The prevalence of low-T3 syndrome increased from 11.1% preoperatively to 38.7% postoperatively. Conclusions: In PDAC, perioperative changes in thyroid hormone indices are pronounced and strongly depend on the type of surgical management. FT3 and the FT3/FT4 ratio appear to reflect systemic metabolic and nutritional adaptation as well as disease burden rather than acting as tumor-specific markers. Full article

Thyroid hormones (THs) are essential regulators of human brain development, and disrupted TH availability during pregnancy or early life is linked to adverse neurodevelopmental outcomes. Concerns that environmental chemicals interfere with TH signalling have increased the need for human-relevant in vitro systems to identify thyroid hormone system-disrupting chemicals (THSDCs) for risk assessment. Here, we compared two human-induced pluripotent stem cell (hiPSC)-derived brain organoid models for THSDC assessment: (i) human cortical organoids (COs) generated by unguided differentiation, offering higher architectural complexity but lower throughput; and (ii) neural stem cell-derived organoids (NSCOs), designed for scalability with reduced cellular diversity. Both models expressed key TH handling components, including the transporter SLC16A2 (MCT8) and the inactivating enzyme DIO3. Using LC–MS/MS, we show that exogenous T3 is depleted from culture media and metabolized to 3,3′-T2 and 3′-T1 in both models, alongside upregulation of T3-responsive genes (HR, KLF9, DIO3, SEMA3C). Pulse and chronic co-exposures to reference disruptors iopanoic acid (IA, deiodinase inhibitor) and silychristin (SC, MCT8 inhibitor) altered T3 metabolism and modulated T3-responsive transcriptional endpoints. In NSCOs, high-content imaging revealed treatment-associated changes in cell composition, with chronic T3 reducing the SOX2-positive progenitor pool and THSDCs blocking this effect. Together, these findings provide a framework for organoid qualification—linking TH handling, transcriptomic responsiveness, and scalable phenotypic readouts—as a necessary step toward model validation and implementation of brain organoids in THSDC risk assessment pipelines. Full article

Background: Thyroid nodules are common, yet only a small proportion are malignant. The independent role of nodule size in malignancy risk remains debated, particularly after adjustment for clinical, biochemical, and sonographic features. Methods: A retrospective cohort study was conducted on adult patients with thyroid nodules evaluated between 2018 and 2025 at a tertiary care center. Clinical, laboratory, ultrasound, cytology, and histopathology data were extracted. Thyroid-stimulating hormone (TSH), free thyroxine (free T4), and sonographic characteristics were analyzed. Univariable and multivariable logistic regression were performed. Missing ultrasound data were addressed using multiple imputation (m = 20), with pooled estimates derived using Rubin’s rules. The final multivariable model included 446 patients. Results: A total of 446 patients were included, of whom 91 (20.4%) had thyroid malignancy. Malignant nodules were significantly larger than benign nodules (2.30 [1.80] cm vs. 1.80 [1.13] cm; p = 0.015). In univariable analysis, TSH, free T4, and multiple ultrasound features were associated with malignancy. In multivariable analysis, nodule size remained the strongest independent predictor of malignancy (adjusted odds ratio [aOR] 1.51; p < 0.001). Hypoechogenicity (aOR 2.07; p = 0.020) and microcalcifications (aOR 1.86; p = 0.047) also remained independently significant, whereas thyroid function parameters were not associated with malignancy after adjustment. Conclusions: Thyroid nodule size is the strongest independent predictor of malignancy, with select ultrasound features retaining additional predictive value. These findings support incorporating nodule size more prominently into thyroid cancer risk stratification while maintaining key sonographic features. Full article

Thyroxine (T4) is a key hormone regulating metabolic, cardiovascular, and neurodevelopmental processes, yet its clinical quantification still relies on centralized immunoassays that limit rapid or point-of-care monitoring. Here, we present a label-free biosensing platform based on silicon nanowire field-effect transistors (SiNW-FETs) functionalized with a T4-selective DNA aptamer via a 3-Triethoxysilyl propylsuccinic Anhydride (TESPSA)-mediated silanization approach, enabling a streamlined two-step modification for oriented immobilization. The biosensor achieves robust real-time detection of T4 across the physiological concentration range (5–30 pM), with a limit of detection of ~5 pM and a strong linear correlation between drain current and analyte concentration (R² = 0.9931). Specificity is confirmed using non-functionalized devices and estradiol as a non-target control. All measurements were performed in undiluted phosphate-buffered saline, representing a physiologically relevant ionic environment and demonstrating stable sensor performance under realistic buffer conditions. The dose–response behavior follows a Hill model, allowing extraction of binding parameters and confirming that the electrical signal originates from specific aptamer–target interactions. These results demonstrate that aptamer-functionalized SiNW-FETs provide a highly sensitive, selective, and miniaturizable platform for quantitative thyroid hormone monitoring, with strong potential for future point-of-care applications. Full article

Background and Objectives: Doxorubicin is an antineoplastic drug used to treat cancer. However, side effects limit its use. Edaravone (EDO) is a recently discovered, powerful drug with antioxidant properties. The aim of the present study was to show the negative effects of doxorubicin and the protective effect of EDO on the thyroid gland using scintigraphic and biochemical methods. Materials and Methods: Thirty-five male Wistar rats were randomly divided into five groups (n = 7) to establish the following study groups: control, doxorubicin, and 1, 10, or 30 mg/kg EDO. DOX (18 mg/kg cumulative intraperitoneal injection (i.p.) was performed on the 19th, 20th, and 21st days of the experiment. EDO (1, 10, and 30 mg/kg) was administered on the first day of the trial and continued for 21 days. These groups also received i.p. injections of DOX (18 mg/kg) on the 19th, 20th, and 21st days of the experiment. On the 22nd day of the experiment, scintigraphic imaging of the thyroid glands of rats was performed using ^99mTc pertechnetate as the radiopharmaceutical. Serum levels of T3, T4, TSH, NLRP3, IL-1β, and IL-18, as well as thyroid tissue levels of MDA, TNF-α, and IL-6, were determined using the ELISA method. Results: DOX significantly reduced ^99mTc pertechnetate uptake in the thyroid gland compared to the control group (p < 0.001). It reduced plasma levels of thyroid hormones T3 (p < 0.001) and T4 (p < 0.001) while increasing TSH levels (p < 0.01). Additionally, NLRP3, IL-1β, IL-18, MDA, TNF-α, and IL-6 levels were significantly increased in the DOX group compared with the control group (all p < 0.001). Pretreatment with EDO significantly attenuated doxorubicin-induced abnormalities in the thyroid gland (p < 0.001). Conclusions: The data from scintigraphic and biochemical analyses revealed the development of hypothyroidism after doxorubicin administration in rats. It was shown that pretreatment with EDO could partially prevent hypothyroidism caused by doxorubicin. Full article

Dexamethasone induces systemic toxicity, including oxidative stress, inflammation, hematological disturbances, and organ damage, particularly in the lungs and thyroid. Taurine exhibits antioxidant and anti-inflammatory properties, but poor bioavailability limits its efficacy. Nanoparticle delivery may enhance stability and tissue targeting. This study aimed to evaluate the protective effects of taurine-loaded chitosan nanoparticles (Tau–CS NPs) against dexamethasone-induced tissue injury in rats. Forty-eight male Wistar rats were allocated into control, DEXA, DEXA + silymarin, DEXA + taurine, and DEXA + Tau–CS NPs groups. Tau–CS NPs were characterized by TEM, UV–vis, FTIR, encapsulation efficiency, and drug loading. Hematology, oxidative stress markers (CAT, SOD, GSH, MDA), thyroid hormones (T3, T4, TSH, calcitonin), protein profile, lung and thyroid histopathology, and MPO expression were assessed. Tau–CS NPs showed uniform spherical morphology (11–60 nm), high encapsulation (98.2%), and substantial loading (50.36%). Dexamethasone caused hematological, oxidative, thyroidal, and histological disturbances. Tau–CS NPs markedly restored hematological indices, antioxidant defenses, thyroid function, protein profile, and tissue architecture, outperforming free taurine and silymarin. MPO expression was significantly reduced, indicating decreased inflammation. Taurine nanoparticles effectively mitigate dexamethasone-induced systemic and organ-specific toxicity, offering improved bioavailability and targeted delivery, highlighting their therapeutic potential. Full article

Background: Non-thyroidal illness syndrome is frequent in critically ill patients, but the prognostic value of dynamic changes in thyroid function tests remains unclear. This study evaluated whether serial measurements of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) provide additional predictive value for 30-day mortality beyond conventional severity scores in ICU patients. Methods: This single-center retrospective observational study included 74 adult patients treated for ≥72 h in a general ICU who had TSH and FT3 measured within 24 h of admission and repeated at 48–72 h. Patients aged 18 years or above admitted to the intensive care unit were included in the study. Demographic characteristics, comorbidities, APACHE II, SOFA, modified NUTRIC (mNUTRIC) scores, and routine laboratory data (including albumin, CRP, and lactate) were recorded. The primary outcome was 30-day mortality. Between-group comparisons were performed using t-tests, Mann–Whitney U, and Chi-square tests. Variables significant in univariate analyses were entered into binary logistic regression models, and predictive performance was assessed using receiver operating characteristic (ROC) curves and the Youden index. Results: The mean age was 68.7 ± 14.7 years, and 41.9% (n = 31) of the patients died within 30 days. Non-survivors had higher APACHE II, SOFA, and mNUTRIC scores and lower albumin, lymphocyte count, and second FT3 levels compared with survivors (all p ≤ 0.003). Baseline FT3 and TSH were not associated with mortality, whereas both the subsequent FT3 measurements and the ΔT3 (variance in former to latter FT3) were remarkably predictive. The latter FT3 < 1.63 pg/mL produced an AUC of 0.835 (sensitivity: 77%, specificity: 74%), and a ΔT3 log ratio threshold of −0.09 (≈20% early FT3 decline) produced an AUC of 0.835 (sensitivity: 71%, specificity: 81%). The APACHE II + ΔT3 (numeric) model showed the best discrimination (AUC: 0.921; sensitivity: 87.1%, specificity: 81.4%), outperforming APACHE II alone (AUC: 0.861). Conclusions: In critically ill adult patients, dynamic T3 kinetics—particularly premature decline in FT3 within the first 72 h—provide incremental prognostic value for 30-day mortality beyond APACHE II. Serial FT3 monitoring may help identify high-risk patients whose endocrine adaptation to critical illness is failing. Full article

Background: The characterization of thyroid lesions is essential in clinical practice. Recent advances in imaging modalities, including nuclear imaging (NM), color Doppler ultrasonography, and sonography, have markedly improved the diagnostic accuracy for thyroid nodules. Objective: To assess thyroid diseases using Doppler ultrasound, nuclear scintigraphy, and sonography. Results: In this cross-sectional single-center study, 144 patients were examined to determine their thyroid structure and function using a multimodal imaging approach. Fine-needle aspiration cytology (FNAC) indicated that most thyroid nodules were benign (62.5%), with 37.5% being malignant. Doppler vascularity demonstrated a sensitivity of 70.4% and a specificity of 40% (AUC = 0.514) for malignancy detection, while scintigraphy uptake in hypofunctioning nodules (nodules with decreased radionuclide uptake) showed a sensitivity of 37% and a specificity of 54.4% (AUC = 0.388). Thyroxine hormone levels showed a sensitivity of 57.4% and a specificity of 45.6% (AUC = 0.503) for detecting malignant thyroid nodules. In multivariate logistic regression, increased Doppler vascularity remained an independent predictor of malignancy (OR = 2.39; 95% CI: 1.15–4.96; p = 0.019), whereas decreased scintigraphic uptake showed a borderline effect (OR = 1.82; p = 0.069); high T4 level and increased uptake were not significant predictors. The combined Doppler ultrasound, scintigraphy, and thyroxine level model yielded an AUC of 0.72 (95% CI: 0.63–0.81), markedly higher than any single parameter. At the optimal Youden threshold (0.43), the model achieved 79.6% sensitivity, 68.2% specificity, and 72.4% accuracy, highlighting the superior diagnostic performance of the integrated approach for pre-FNAC stratification of thyroid malignancies. There was a strong, significant linear association between thyroxine levels and thyroid scintigraphy uptake (p-value < 0.001). Most patients with normal thyroxine levels exhibited decreased uptake (66.1%), whereas a minority (6.5%) demonstrated elevated uptake levels. This study found a strong correlation between mixed-echogenicity nodules and thyroid scintigraphy uptake (p-value = 0.019). Mixed-echogenicity nodules were most often associated with reduced uptake (57.8%), and hypoechoic nodules often had normal uptake (57.1%). Conclusions: The complementary integration of color Doppler vascularity, Tc-99m thyroid scintigraphy, and serum thyroxine levels yields superior Doppler–scintigraphy uptake correlation, increases the overall diagnostic accuracy, and offers a practical, non-invasive algorithm for differentiating benign from malignant thyroid nodules prior to FNAC or surgery. Full article

This study was conducted to evaluate the effect of varying dietary energy levels on milk production, feed intake, nutrient digestion and metabolism, and antioxidation function of lactating donkeys, and integrating 16S rRNA gene sequencing, metabolomics, and proteomics to comprehensively reveal the underlying regulatory networks. A single-factor, completely randomized design was used in this study. Twenty-four Dezhou donkeys with similar milk yield (3.25 ± 0.46 kg/d), lactation days (29 ± 4.34 d), parities (4.17 ± 1.17), and body weight (256 ± 34 kg) were randomly divided into three dietary treatments (n = 8), and either a fed high-energy diet (DE = 13.1 MJ/kg, HED), medium-energy diet (DE = 12.4 MJ/kg, MED), and low-energy diet (DE = 11.7 MJ/kg, LED). The experiment period included 2 weeks for adaptation and 8 weeks for data and sample collection. Orthogonal polynomial contrasts were used to evaluate the linear and quadratic effects of increasing dietary energy. There were no significant interaction effects between dietary energy level and lactation week on any milk production and quality variables (p > 0.05). Increasing dietary energy level increased DMI, milk production, milk production efficiency, and milk components (linear and quadratic; p < 0.05). Increasing dietary energy improved the digestibility of DM and neutral detergent fiber (linear; p < 0.05), and crude protein digestibility, energy digestibility and metabolism, and nitrogen metabolism (quadratic; p < 0.05). However, it decreased BHBA and NEFA concentrations (linear; p < 0.05). Furthermore, increasing dietary energy first increased then decreased the activities of GSH-PX, SOD, and T-AOC (linear and quadratic; p < 0.05), while increasing the MDA content (linear; p < 0.05). Compared with HED and MED, LED increased the relative abundance of the genera unclassified_f_Syntrophomonadaceae, Christensenellaceae_R-7_group and Treponema_2. Compared with HED, MED increased the relative abundance of the genera Ruminiclostridium_5, Ruminiclostridium_1, Family_XIII_UCG-001, unclassified_o__Clostridiales and norank_f__PL-11B10. Thyroid hormone synthesis, tyrosine metabolism, and glutathione metabolism pathways are critical metabolic routes; these pathways can enhance energy metabolism and antioxidant function, thereby improving the milk production performance of lactating donkeys. In conclusion, the digestible energy of 12.40 MJ/kg was optimal for the milk performance of lactating donkeys, whereas excessively high dietary energy (13.1 MJ/kg) may reduce milk performance. Full article

Introduction: Hashimoto’s thyroiditis (HT) is the leading cause of hypothyroidism in iodine-sufficient regions and often presents with subclinical hypothyroidism. Selenium (Sel) has immunomodulatory effects, while myo-inositol (MI) may enhance thyroid-stimulating hormone (TSH) signaling. This study evaluated whether adding myo-inositol to selenium provides additional benefit compared with selenium alone in these patients. Methods: A systematic search of PubMed, Web of Science, and the Cochrane Library was conducted from inception to 7 March 2026. Studies comparing myo-inositol plus selenium (MI + Sel) with Sel monotherapy were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a frequentist random-effects model. Outcomes of interest included TSH, free T3 and T4, thyroglobulin antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb). Trial sequential analysis (TSA) was performed to assess the robustness of significant findings. Results: Three studies involving 288 patients were included (151 receiving MI + Sel and 137 receiving Sel alone). Combination therapy significantly reduced TSH levels compared with Sel monotherapy (SMD −1.26; 95% CI −1.51 to −1.00; p < 0.01; I² = 0%), and TSA suggested that this finding may be robust, although the evidence is limited by the small number of studies. TgAb levels were also significantly reduced (SMD −0.51; 95% CI −0.78 to −0.24; p < 0.01; I² = 0%); however, TSA indicated a potential risk of type I error. No significant differences were observed for T3 (SMD 0.15; 95% CI −0.09 to 0.38; p = 0.22; I² = 7%), T4 (SMD −0.01; 95% CI −0.72 to 0.69; p = 0.97; I² = 88%), or TPOAb (SMD −0.18; 95% CI −0.44 to 0.09; p = 0.20; I² = 0%). Conclusions: MI combined with Sel was associated with a significant reduction in TSH levels compared with Sel alone in patients with HT and subclinical hypothyroidism, suggesting a potential therapeutic benefit. However, given the limited number of studies, these findings should be interpreted with caution. Further large randomized controlled trials are required to confirm the effects on thyroid function and autoimmunity. Full article

Background: Surgical trauma disrupts hormone networks, but the duration required for these systems to recover remains unclear. We hypothesize that significant perioperative stress would trigger protracted abnormalities of the thyroid axis extending past 28 days. Methods: This retrospective exploratory study analyzed opportunistically obtained thyroid-related laboratory values (free T3 [FT3], free T4 [FT4], and thyroid-stimulating hormone [TSH]) and serum albumin from electronic medical records of patients undergoing CABG, AVR, or PCI between 2017 and 2022. Preprocedural baseline values were compared with post-procedural serum levels measured during the acute peri-procedural period (0–30 days), early recovery (31–90 days), intermediate recovery (91–180 days), late recovery (181–365 days), medium-term follow-up (1–2 years), and long-term follow-up (>2 years). Results: Free T3 demonstrated early suppression across all procedures, most pronounced in CABG during the acute peri-procedural period, with partial recovery at later timepoints. AVR showed moderate suppression at early and long-term follow-up, while PCI demonstrated minimal and inconsistent changes. Free T4 remained relatively stable across procedures, with limited significant post hoc differences after adjustment. TSH showed significant temporal variability in CABG and AVR but not in PCI. Serum albumin demonstrated marked early decline, most pronounced in CABG, with partial recovery over time, whereas AVR showed delayed long-term suppression. Data availability declined substantially at later timepoints across all biomarkers. Conclusions: In this retrospective exploratory analysis, CABG was associated with the most pronounced early perturbations in thyroid and albumin trajectories, while PCI and AVR demonstrated more heterogeneous temporal patterns. These findings are hypothesis-generating and should be interpreted cautiously given non-protocolized laboratory follow-up, substantial missingness, and potential selection bias. Full article