Free Thyroxine Research Articles

Association of Free Thyroxine with Progression-Free Survival in Intermediate and High Risk Differentiated Thyroid Cancer.

Supraphysiologic thyroxine (T4) doses are used in intermediate and high-risk patients with differentiated thyroid cancer (IR/HR-DTC) to suppress tumor progression by thyrotropin (TSH). However, preclinical data suggest that T4 can also act as a growth stimulus for cancer, but there is no clinical evidence supporting this claim. We analyzed the association between free T4 (FT4) and progression-free survival (PFS) in patients with IR/HR-DTC. This longitudinal cohort study, approved by multi-institutional review board, included patients with IR/HR-DTC treated uniformly with total thyroidectomy, radioiodine (RAI), and TSH suppression therapy, with at least three TSH and FT4 values available. Association between FT4 and PFS at landmarks 6, 12, and 18 months was assessed by Kaplan-Meier survival curves, while competing risks were assessed through Cox proportional hazards model. From 739 screened patients 382 met the inclusion criteria and were characterized by a median age of 46 (34-59) years, 64.1% women, treated with a median RAI dosage of 159 (110-410) mCi. During follow up of 7.1 (3.4-12.7) years 34.6% experienced disease progression.Elevated FT4, observed in 29.3% of patients, was not associated with worse PFS (HR 0.9, CI 0.54-1.5, p=0.69), while age (HR 1.02, CI 1.004-1.04, p=0.01), tumor size (HR 1.15, CI 1.04-1.28, p=0.01), and metastases to the lateral neck lymph nodes (HR 2.9, CI 1.7-4.74, p<0.001), bones (HR 4.87, CI 1.79-13.3, p=0.002), and brain (HR 5.56, CI 2.54-12.2, p<0.001) were associated with shorter PFS. Contrary to preclinical evidence, elevated FT4 levels do not affect PFS in patients with IR/HR-DTC.

A comprehensive investigation of biochemical status in patients with telogen effluvium: Analysis of Hb, ferritin, vitamin B12, vitamin D, thyroid function tests, zinc, copper, biotin, and selenium levels.

The etiology of telogen effluvium (TE) includes situations that may cause physiological stress, surgical trauma, inflammatory, infectious, iatrogenic causes, medications and nutritional deficiencies. TE has been associated with iron deficiency, vitamin B12 deficiency and thyroid diseases. In recent years, the use of over-the-counter food supplements containing vitamins and minerals such as biotin, vitamin D, zinc (Zn), copper (Cu) and selenium (Se) has been increasing in TE patients. The aim of this study is to investigate whether there are differences in nutritional status, vitamin and mineral levels by comparing individuals with TE and a control group. This case-control study included 90 female patients diagnosed with chronic telogen effluvium (CTE), and 90 female controls volunteered to participate in the study who consulted for reasons other than TE. Both groups aged 18 and over and applied to dermatology polyclinic between 01.09.2022 and 01.09.2023. A detailed anamnesis was taken from all patients, a hair pull test was performed, and TE was diagnosed after a dermoscopic examination was performed on all areas of the scalp. Then, serum vitamin D, Zn, Cu, Se levels and biotin levels in serum and urine were measured. Hemoglobin (Hb), ferritin, vitamin B12 and thyroid function tests were retrospectively scanned from the hospital database. It was determined that Zn levels were significantly lower in CTE patients than in controls. Se levels were found to be significantly higher in patients than in controls. There was no difference in Hb, ferritin, vitamin B12, thyroid function tests, vitamin D, Cu levels, serum and urine biotin levels between the two groups. Zn, Cu/Zn and Se levels were found to have statistically significant diagnostic performance in predicting the diagnosis of CTE. Cu/Zn ratio and Se value were found to be significant predictors of CTE. This study shows us that nutritional deficiencies are not as common as thought in patients diagnosed with TE. Other causes that may cause TE should be investigated by a detailed anamnesis and a good physical examination. After all, tests for suspected conditions should be performed and individualized treatment options should be created for each patient.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008

Background and purposeHypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. Materials and methodsIn 2012–2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. ResultsThe analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3–9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632–36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001–0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999–1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. ConclusionThe study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

The importance and prognostic effect of thyroid hormones in patients with transposition of the great arteries

Objectives: Transposition of the great arteries (TGA) is a rare congenital heart disease that occurs in 3 in 10,000 newborns and is rapidly fatal (90%) within one year if left untreated. The prognosis of this pathology changed after introducing an early arterial switch operation (ASO), while the left ventricle could still adapt to systemic high-pressure conditions. Appropriate regulation of thyroid hormones positively impacts metabolism, cardiac function, and postoperative recovery. Therefore, regular thyroid hormone monitoring and thyroid function monitoring of TGA patients may help to improve the health status and prognosis of this group of postoperative patients. Methods: In our study, 127 patients who underwent ASO at our pediatric cardiac surgery clinic between 01.01.2014 and 18.09.2021 were retrospectively analyzed and included. Among the patients, 43% (n=54) were females, and 57% (n=73) were males. Results: The coronary arteries were normal in 89.7% (n=114) and abnormal in 10.3% (n=13) of the patients. Twenty-one of the patients exited, and mortality was calculated to be 16.5%. There were no significant differences in mortality or thyroid stimulating hormone (TSH), free thyroxine (T4), or free triiodothyronine (T3) values (P=0.674, P=0.345, P=0.478). In our study, in which we investigated the effect of thyroid hormone levels on prognosis in neonatal patients with TGA with normal free T3, T4, and TSH values, we found that TSH levels were greater in the group with advanced aortic regurgitation and exitus, although the effect of thyroid hormones on postoperative results was not statistically significant. Conclusions: Congenital hypothyroidism is a common disease with cardiac effects. During the neonatal period, this disease may conceal itself. Careful, expert clinical follow-up and clinical trials are crucial to improve outcomes in the surgical treatment of transposition of the great arteries, a complex congenital heart disease.

Investigation of Metabolic Parameters of Women of Reproductive Age

Objective: Fertility rates are decreasing every year, mainly due to socioeconomic and medical reasons. In this study we aimed to investigate the incidence of metabolic disorders that may negatively affect reproduction. Methods: Glucose parameters of 5892 patients, lipid parameters of 2491 patients and thyroid function tests of 457 patients were retrospectively examined. Patients divided into two groups in terms of age. Each age groups were divided into subgroups as diabetic, prediabetic, non-diabetic and euthyroidism, overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism. Results: The rate of Euthyroidism was 85.8%, overt hypothyroidism was 4.2%, subclinical hypothyroidism was 3.5%, and hyperthyroidism (subclinical+overt) was 6.5% in all ages. There was no significant difference in st3, st4 and TSH values according to age (p values p = 0.051, p = 0.195, p = 0.585, respectively). The rate of diabetes was 4.7%, non-diabetes 83.7% and prediabetes was 11.6%. There was a significant difference between diabetic, prediabetic, and non-diabetic according to age (p≤0.001). Conclusion: Thyroid dysfunction and glucose metabolism disorders are more common in our country due to genetic and environmental factors. Early diagnosis is very important to avoid the unwilling side effects of this condition. For this, new approaches are needed, such as close follow-up clinics aimed only at women of reproductive age.

Normal Values for the fT3/fT4 Ratio: Centile Charts (0–29 Years) and Their Application for the Differential Diagnosis of Children with Developmental Delay

Primary congenital hypothyroidism is easily diagnosed on the basis of elevated plasma levels of thyroid-stimulating hormone (TSH). In contrast, in the rare disorders of thyroid hormone resistance, TSH and, in mild cases, also thyroid hormone levels are within the normal range. Thyroid hormone resistance is caused by defects in hormone metabolism, transport, or receptor activation and can have the same serious consequences for child development as congenital hypothyroidism. A total of n = 23,522 data points from a large cohort of children and young adults were used to generate normal values and sex-specific percentiles for the ratio of free triiodothyronine (T3) to free thyroxine (T4), the fT3/fT4 ratio. The aim was to determine whether individuals with developmental delay and genetically confirmed thyroid hormone resistance, carrying defects in Monocarboxylate Transporter 8 (MCT8), Thyroid Hormone Receptor alpha (THRα), and Selenocysteine Insertion Sequence-Binding Protein 2 (SECISBP2), had abnormal fT3/fT4 ratios. Indeed, we were able to demonstrate a clear separation of patient values for the fT3/fT4 ratio from normal and pathological controls (e.g., children with severe cerebral palsy). We therefore recommend using the fT3/fT4 ratio as a readily available screening parameter in children with developmental delay for the identification of thyroid hormone resistance syndromes. The fT3/fT4 ratio can be easily plotted on centile charts using our free online tool, which accepts various SI and non-SI units for fT3, fT4, and TSH.

Hypothyroidism in Older Adults: A Concise Review of the Recent Literature

Abstract Introduction Hypothyroidism (HypoT) is a common condition whose prevalence varies according to regional and ethnic factors, dietary iodine, gender, and age. The symptoms of HypoT are generally nonspecific, with considerable overlap with other conditions. These symptoms are not useful for diagnosing HypoT, and a thyroid function test is required for a final diagnosis. Materials and methods We aimed to provide an overview of the recent global literature on HypoT in older adults. A narrative, nonsystematic review of the international literature from a single major medical online database (PubMed) for the past 5 years was performed. The relevant literature was narrated in a concise thematic account. Results Most studies and expert opinions reiterated the benefit of replacement therapy in younger and middle-aged individuals. A good volume of literature also considered the interplay between thyroid hormones and (1) cardiovascular function and risk factors, (2) cognitive function, (3) mental health, and (4) quality of life. Most workers are cognizant of the important difference in normal ranges of thyroid-stimulating hormone (TSH) and the consequent TSH targets in older adults compared to younger age groups. Extra care is recommended for the initiation and titration of thyroid hormone replacement therapy to avoid cardiovascular and skeletal adverse effects of relative overtreatment. Conclusion While clinical benefit is evident in patients under age 65 with overt and subclinical HypoT who are treated with levothyroxine, treatment may be harmful in older adults with subclinical HypoT. The 97th percentile of TSH distribution is 7.5 mIU/L for patients over age 80. Hence, TSH goals should be individualized in older adults to achieve any possible benefit and avoid unnecessary harm.

Preoperative Thyroid-Stimulating Hormone Levels and Three-Year Mortality in Elderly Hip Fracture Patients: Insights from a Prospective Cohort Study.

BACKGROUND It is unclear whether preoperative thyroid-stimulating hormone (TSH) level is correlated with long-term mortality in the elderly after hip fracture surgery. We aimed to assess the association between TSH levels and 3-year mortality in these patients. MATERIAL AND METHODS We enrolled patients aged 65 and above who had hip fracture surgery and thyroid function tests upon admission from 2018 to 2019. Patients were categorized based on TSH median value, quartiles, or thyroid function status. The median follow-up time was 3.1 years. Cox proportional hazards models were used to examine the correlation between TSH levels and mortality, adjusting for covariates. RESULTS Out of 799 eligible patients, 92.7% (741/799) completed the follow-up, with 20.6% (153/741) of those having died by the end of the follow-up. No statistically significant differences in mortality risks were found when stratified by TSH median value (HR 0.88, 95% CI 0.64-1.22, P=0.448) or quartiles (HR ranging from 0.90 to 1.13, P>0.05). Similarly, when categorized based on admission thyroid function status, patients who presented with hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism upon admission did not demonstrate a statistically significant difference in mortality risk compared to those who were considered euthyroid (HR 1.34, 95% CI 0.72-2.49, P=0.359; HR 0.77, 95% CI 0.38-1.60, P=0.489; HR 1.15, 95% CI 0.16-8.30, P=0.890; HR 1.07, 95% CI 0.34-3.38, P=0.913, respectively). CONCLUSIONS Admission TSH is not significantly associated with 3-year mortality in geriatric patients after hip fracture surgery.

Exploring serum amino acid signatures as potential biomarkers in Hashimoto's thyroiditis patients.

Hashimoto's thyroiditis (HT) is an autoimmune disease caused by the immune system attacking healthy tissues. However, the exact pathogenesis of HT remains unclear. Metabolomic analysis was performed to obtain information about the possible pathogenic mechanisms and diagnostic biomarkers of HT. The amino acid profile was analyzed using an LC-MS/MS method using serum samples obtained from 30 patients diagnosed with ultrasonographic imaging and laboratory markers (thyroid stimulating hormone) free thyroxine and thyroid peroxidase) and 30 healthy individuals. There were statistically significant changes in 27 amino acids out of 32 amino acids analyzed (p < 0.05). Based on the receiver operating characteristic curve analysis, the six amino acid (1-methylhistidine, cystine, norvaline, histidine, glutamic acid and leucine) biomarkers showed high sensitivity, specificity (area under the curve > 0.98), positive likelihood ratio and low negative likelihood ratio. Also, according to pathway analysis, degradation of phenylalanine, tyrosine and tryptophan biosynthesis was the highest metabolic pathway according to the impact value (p < 0.001 and impact value = 1.0). We provide serum amino acid profiles of patients with Hashimoto's thyroiditis and identify five potential biomarkers for early diagnosis by clinicians.

Surgical Outcomes in Thyroidectomy for Patients with Graves’ Disease: A Randomized Controlled Trial

Background: Thyroidectomy is a preferred protocol for patients with Graves’ disease. However, it may be a challenging option in post-surgical management of various factors. There, this study aims to compare the surgical outcomes of total thyroidectomy and subtotal thyroidectomy in patients with Graves’ disease to provide evidence-based surgical decision-making. Methods: This randomized controlled trial was conducted at Sheikh Zaid Hospital, Rahim Yar Khan, October 2023 to April 2024; enrolled 120 patients diagnosed with Graves’ disease using a simple random sampling technique were assigned to Group A (n=60) and B (n=60) who underwent total thyroidectomy, and subtotal thyroidectomy respectively. Preoperative assessments and surgeries were performed while postoperative outcomes, complications, and thyroid function tests were also monitored and represented using independent t-tests while a p&lt;0.05 was considered significant. Results: It was revealed that operative time was significantly higher for total thyroidectomy than subtotal thyroidectomy 125.60±14.56 and 97.54±12.56 respectively, suggesting significantly lower time consumption in subtotal thyroidectomy procedure (p=0.001). Patients who underwent subtotal thyroidectomy had a significantly shorter hospital stay compared to those who underwent total thyroidectomy (p=0.02). Moreover, levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were significantly different between the two groups. Patients who underwent subtotal thyroidectomy had significantly lower T3 and T4 levels and higher TSH levels compared to those who underwent total thyroidectomy (p&lt;0.05). Conclusion: Subtotal thyroidectomy demonstrated favorable outcomes, including shorter operative time, lower rates of postoperative complications, and thyroid function tests compared to total thyroidectomy. These findings help and support the consideration of subtotal thyroidectomy as a viable surgical approach for patients with Graves' disease. Keywords: Grave Disease, Thyroidectomy, Thyroxine, Triiodothyronine.

Application of health belief model to assess periodic examination of thyroid functions in children among Saudi mothers

Background: Hypothyroidism is a common concern in the development of physical and cognitive development in children. The health belief model is one of the models that examines the factors behind people’s behaviors. Aim was to assess the periodic examination of children among Saudi mothers and its association with different constructs of the health belief model. Methods: This cross-sectional study was conducted among 385 participants of Saudi mothers for three months from January to April 2024 by using a designed structured questionnaire. Results: 88.05% of mothers showed poor behavior regarding periodic examinations of thyroid functions for their children. The significant factors that determined this behavior were the older mother’s age, working status (mother working), positive family history of hypothyroidism, good perceived benefits, and good cues to action. These factors were statistically significant at p value &lt;0.05. Conclusions: Most of the mothers who participated in this study showed poor behavior regarding the regular examination of thyroid function tests of their children. Factors such as the older mother’s age, working status (working mother), positive family history of thyroid issues, good perceived benefits of the exams, and good cues to action were found to be significantly associated with mothers’ behavior towards this regular examination of thyroid function.

Total triiodothyronine level associated with disease severity for patients with emergent status

Thyroid hormones are metabolic indicators to evaluate the physical condition of emergency hospitalized patients, while the relationship between total triiodothyronine and the severity of emergency inpatients is still unclear. To explore the thyroid function levels of inpatients in emergency ward and the status of combined Nonthyroidal illness syndrome (NTIS), and to emphasize the importance of thyroid hormone examination for non-endocrinology inpatients. According to thyroid function of inpatients in emergency ward, they were divided into NTIS group and non-NTIS group, the hematological characteristics and TH levels of each group were analyzed. Based on clinical diagnoses, the hospitalized patients were divided into three major groups, namely infection group, non-infection group and impaired organ function group. Among them, infection group was further divided into sepsis group, lung infection group and local infection group, altogether five groups. The thyroid function levels and low values in each group were evaluated, and the correlation between hormone levels and inflammatory factors, nutritional indicators and the relationship with the risk of death was discussed. The inpatient rate in emergency ward complicated with NTIS was 62.29%, T3 was the most sensitive index of NTIS, followed by FT3. Compared to non-NTIS group, the NTIS group had an increased risk of death. The sepsis group and impaired organ function group had the highest rates of complicated NTIS, reaching 83.33% and 78.12% respectively. Spearman's correlation analysis implied T3/T4/FT3 levels were positively correlated with ALb and PLT (except T4), and negatively correlated with CRP, D-Dimer, IL-6 and Fer. The Receiver Operating Curve (ROC) and Area under the curve (AUC) showed T3 levels alone were strongly associated with the risk of death (AUC 0.750; 95% CI 0.673–0.828; P < 0.001). T3 is the most sensitive indicator for emergency patients, followed by FT3. The decrease of T3 level has a good predictive value for mortality risk. Thyroid function should be monitored in critically ill patients.

Prevalence of Thyrotropin Receptor Antibodies and Clinical Profile of Patients with Alopecia Areata: A Cross-Sectional Study

Introduction: Alopecia areata (AA) is associated with thyroid dysfunction and abnormal levels of thyroglobulin and thyroid peroxidase autoantibodies. One study detected high prevalence of thyrotropin receptor antibodies (TRAbs) in AA patients. Our aim was to investigate the prevalence of TRAb levels in AA patients and to assess their association with thyroid hormones, other thyroid antibodies, AA severity, and other epidemiological variables. Methods: In this observational study, 139 patients (97 females, 42 males), aged 12 and above, with newly presenting, relapsing, or treatment-resistant AA were included. Medical histories were reviewed, alopecia severity was assessed using the Severity of Alopecia Tool (SALT), and blood tests measured thyroid hormones and autoantibodies. Results: The prevalence of TRAb was significantly higher in AA patients (23.6%) compared to the general population (1–2%) (p < 0.001). Elevated TRAb titers did not correlate with diagnosed thyroid dysfunction or treatment, abnormal thyroid function tests and autoantibodies, AA severity, duration, and onset. Male patients exhibited a significantly higher prevalence of abnormal TRAb titers compared to females (75.0% vs. 21.3%, p = 0.002). Conclusion: A significant proportion of AA patients presented with elevated TRAb levels, independent of thyroid hormone titers, other thyroid autoantibodies, or SALT score. Prevalence of abnormal TRAb levels was higher in males.

Acute radiation skin injury in stage III-IV head and neck cancer: scale correlates and predictive model

PurposeActive radiation skin injury (ARSI) has the highest incidence of acute adverse reactions caused by radiotherapy (RT) in patients with head and neck cancer (HNC). This study aimed to screen risk factors that can facilitate the identification of HNC patients at high risk of ARSI.MethodsData from 255 stage III-IV HNC patients who underwent intensity-modulated radiation therapy (IMRT) were collected. The data from our medical records, including clinical characteristics and hematological indices before RT, were retrospectively collected and arranged. The Common Terminology Criteria for Adverse Events Criteria (CTCAE), Radiation Therapy Oncology Group Criteria (RTOG), World Health Organization Criteria (WHO), Oncology Nursing Society (ONS), Acute Radiation Dermatitis Graduation Scale, Douglas & Fowler and Radiation Dermatitis Severity Scale (RDSS) were used to assess ARSI. Of these, CTCAE was used for further analysis. Binary logistic regression analyses were used to identity risk factors. To establish the correction between each risk factor and the ARSI score, the odds ratio (OR) and 95% confidence interval (CI) were computed.ResultsThe assessment results of the CTCAE with RTOG, WHO, ONS, Graduation Scale, Douglas & Fowler and RDSS have good consistency. After radiotherapy, 18.4% of patients had at least 3 (3 +) grade ARSI. Multivariate logistic regression analysis revealed that the KPS score, blood glucose level, white blood cell count, and plasma free thyroxine (FT4) concentration were independent risk factors for 3 + grade ARSI. A nomogram was constructed on the basis of these risk factors, which demonstrated good predictive power according to the area under the ROC curve (AUC). The satisfactory consistency and clinical efficacy of the nomogram were confirmed by calibration curves and decision curve analysis (DCA).ConclusionA low KPS score, high blood glucose level, high white blood cell count, and high thyroid hormone prior to radiotherapy for stage III-IV HNC are independent risk factors for grade 3 + RSI.

The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study

BackgroundThe aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them.MethodsA two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis.ResultsA genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females.ConclusionsGenetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Moderation of thyroid hormones for the relationship between amyloid and tau pathology

BackgroundAltered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.MethodsThis cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET.ResultsNo associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.ConclusionOur findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

Correlation analysis between serum free triiodothyronine and C-peptide-based insulin resistance index in euthyroid adults

Objective: To explore the correlation between serum free triiodothyronine (FT3) and C-peptide-based insulin resistance index (HOMA2 IR-CP) in euthyroid adults. Methods: A cross-sectional study. The clinical data of euthyroid adult participants who underwent physical examination in the Second Medical Center of Chinese PLA General Hospital from January to December in 2019 were retrospectively analyzed. According to the HOMA2 IR-CP level, the participants were divided into HOMA2 IR-CP>2.18 group (n=3 463) and HOMA2 IR-CP≤2.18 group (n=8 204). Univariate Pearson correlation analysis and multivariate logistic regression analysis were used to analyze the correlation between FT3 and HOMA2 IR-CP. The interaction model was used to analyze the interaction between FT3 and related factors, and the dose-response relationship between continuity variable FT3 and HOMA2 IR-CP was explored by using restricted cubic spline plots. Results: A total of 11 667 euthyroid adult participants aged (50.7±10.0)years were recruited according to the inclusion and exclusion criteria, with 7 756 males and 3 911 females. The proportion of males, body mass index, systolic blood pressure, glycated hemoglobin A1c, fasting plasma glucose, triglyceride, hemoglobin, alanine aminotransferase and FT3 levels in HOMA2 IR-CP>2.18 group were significantly higher than those in HOMA2 IR-CP≤2.18 group (all P<0.05). The levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and free thyroxine in HOMA2 IR-CP>2.18 group were lower than those in HOMA2 IR-CP≤2.18 group (all P<0.001). Univariate Pearson correlation analysis showed that FT3 was associated with HOMA2 IR-CP (r=0.21, P<0.001). Multivariate logistic regression analysis suggested an association between FT3 and HOMA2 IR-CP after adjusting for confounding factors(Pfor trend<0.001). Subgroup analysis showed an association between FT3 and HOMA2 IR-CP in different subgroups of gender, age and glucose metabolism status (Pfor trend<0.05). Multiplication interaction analysis suggested that there was an interaction between FT3 and age (Pinteraction<0.001). Restricted cubic spline model analysis demonstrated that the correlation between FT3 and HOMA2 IR-CP was linear (Poverall<0.001, Pnonlinear=0.479). Conclusions: There is a correlation between serum FT3 and HOMA2 IR-CP in euthyroid adults. With the increase of FT3 level, insulin resistance increases gradually.

Sex Differences in Physiological Responses to a National Collegiate Athletic Association Division I Soccer Season.

McFadden, BA, Walker, AJ, Cintineo, HP, Bozzini, BN, Sanders, DJ, Chandler, AJ, and Arent, SM. Sex differences in physiological responses to a national collegiate athletic association division I soccer season. J Strength Cond Res XX(X): 000-000, 2024-Identifying physiological changes that occur in response to workload demands can help to elucidate athlete management and recovery strategies. The purpose of this study was to compare the physical and physiological demands between men and women throughout the course of a collegiate soccer season. Men (N = 23) and women (N = 26) soccer players participated in blood draws before preseason (T1) and every 4 weeks thereafter (T2-T4). Workload was determined at all practices and games via heart rate and global positioning satellite monitoring systems. Repeated measures multivariate analysis of variance and linear mixed models were used to assess workload and biomarker responses throughout the season (p < 0.05). Both teams experienced the highest workloads during the first 4 weeks of the season (p < 0.05), which was followed by several biomarker perturbations. Sex-by-Time interactions were observed for total cortisol, growth hormone, insulin-like growth factor-1, thyroxine, thyroid-stimulating hormone, vitamin D, and omega 3 fatty acid index (p < 0.05). Additional Sex effects were observed for free and total testosterone, estrogen, prolactin, sex-hormone binding globulin, creatine kinase, and iron levels (p < 0.05). Women soccer players experienced further Time effects for free cortisol, iron, ferritin, and percent transferrin saturation (p < 0.05). Male soccer players experienced additional Time effects for total testosterone, estrogen, creatine kinase, interleukin-6, triiodothyronine, and ferritin (p < 0.05). Despite similar patterns of change in workloads, differential fluctuations in physiological markers were observed between the sexes. Understanding sex differences in response to comparable workloads may enhance exercise prescriptions for better athlete management plans. Additional strategies to increase iron may be warranted in female athletes.

Role of Nannochloropsis Oculata supplement in improving performance, antioxidant status, blood metabolites, and egg quality of laying hens under hot environmental conditions

The increase in environmental temperature led to economic losses in the poultry industry, urging the use of feed supplements to mitigate the negative effects on chick's welfare and performance. Therefore, this study aimed to examine the effects of marine microalgae (Nannochloropsis Oculata, N. Oculata) additive on commercial Brown Lohmann laying hen's performance, blood metabolites, and antioxidant status under hot environmental conditions. One hundred and eighty birds (34 weeks old with an initial body weight of 1885 ± 23.5 g) were used till 47 weeks. The birds were divided into three equal groups (birds in each group were distributed into four equal replicates 15 hens/ replicate). The 1st group was the control (CON) and was fed the basal diet, while the 2nd (TR1) and 3rd (TR2) groups were fed the basal diet supplemented with 0.5 and 1.0% of N. Oculata, respectively. The results showed that total protein and globulin concentrations increased (P < 0.05) in treated groups compared with the control group, whereas, albumin concentration increased (P < 0.05) in TR2 compared to the control group. The concentration of ALT and AST decreased in hens fed N. Oculata. Supplementing with N. Oculata reduced serum cholesterol and creatinine concentrations, while glucose concentration increased (P < 0.05) in the treated groups compared to the control group. Serum calcium, total antioxidant capacity (TAC), Triiodothyronine (T3), and progesterone increased (P < 0.05) in hens fed N. Oculata. N. Oculata supplement improved production performance through a positive effect on egg number, egg weight, egg mass, feed conversion ratio, and mortality rate. In addition, the overall mean of shell thickness increased (P < 0.05) in hens fed N. Oculata. It can be concluded that the supplementation of 1.0% N. Oculata to the laying hens' diet enhanced productive performance, serum constituents, and antioxidant status under hot environmental conditions.

Patterns of thyroid gland dysfunction among hospitalized patients with COVID-19 pneumonia

BackgroundSince the onset of the COVID-19 pandemic, multiple studies have reported a bidirectional between COVID-19 and dysfunction of the thyroid gland. These studies have identified various forms of thyroid dysfunction that have been found to affect the severity and outcome of COVID-19 infection. However, the data from these studies have been inconsistent and conflicting. Our objective was to assess the prevalence of various types of thyroid dysfunction among moderate to severe cases of COVID-19 pneumonia. In addition, the study aimed to evaluate the outcome of thyroid dysfunction after recovery from COVID-19 infection.Patient and methodsIn this observational prospective study data on the clinical features of individuals with moderate to severe COVID-19 pneumonia who were admitted to Zagazig University isolation hospitals from April to December 2022 and their laboratory results were gathered and examined. Thyroid function tests, including TSH, FT3, and FT4, were conducted for all patients upon admission. Follow-up testing was performed on patients who initially had aberrant thyroid lab results 90 days after recovering from COVID-19 infection.ResultsThe study comprised a total of 136 patients who had moderate (44.1%) to severe (55.9%) COVID-19 infection. Sick euthyroid syndrome was the most prevalent form of thyroid dysfunction, accounting for 58.7% of patients with thyroid disorders on admission. After 90 days of post-COVID-19 examination, thyroid dysfunction recovery was observed in 61% of cases. A statistically significant correlation was noted between the severity of COVID-19 and the levels of TSH, free T3, and the ratio of free T3 to T4. A large percentage of patients who showed complete recovery had sick euthyroid syndrome. All patients diagnosed with primary hypothyroidism maintained their hypothyroidism condition, whereas those with hyperthyroidism showed complete recovery.ConclusionCOVID-19 patients may experience several patterns of thyroid dysfunction, including nonthyroidal illness syndrome. These dysfunctions are associated with the intensity of the inflammatory response and the severity of the COVID-19 infection. Nevertheless, these alterations are predominantly reversible upon recovery from a COVID-19 infection.