FT4 Concentrations Research Articles

Rapid supervised levothyroxine absorption test in refractory hypothyroidism: suggestion for assessing absorption using two blood samples in low-resource settings.

Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student's t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4-170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.

Predicting Factors of Worse Prognosis in COVID-19: Results from a Cross-sectional Study on 52 Inpatients Admitted to the Internal Medicine Department.

The initial phases of the COVID-19 pandemic posed a real need for clinicians to identify patients at risk of poor prognosis as soon as possible after hospital admission. The study aimed to assess the role of baseline anamnestic information, clinical parameters, instrumental examination, and serum biomarkers in predicting adverse outcomes of COVID-19 in a hospital setting of Internal Medicine. Fifty-two inpatients consecutively admitted to the Unit of Internal Medicine "Baccelli," Azienda Ospedaliero - Universitaria Policlinico of Bari (February 1 - May 31, 2021) due to confirmed COVID-19 were grouped into two categories based on the specific outcome: good prognosis (n=44), patients discharged at home after the acute phase of the infection; poor prognosis, a composite outcome of deaths and intensive care requirements (n=8). Data were extracted from medical records of patients who provided written informed consent to participate. The two study groups had similar demographic, anthropometric, clinical, and radiological characteristics. Higher interleukin 6 (IL-6) levels and leucocyte count, and lower free triiodothyronine (fT3) levels were found in patients with poor than those with good prognosis. Higher IL-6 levels and leucocyte count, lower fT3 concentration, and pre-existing hypercholesterolemia were independent risk factors of poor outcomes in our study population. A predicting risk score, built by assigning one point if fT3 < 2 pg/mL, IL-6 >25 pg/mL, and leucocyte count >7,000 n/mm3, revealed that patients totalizing at least 2 points by applying the predicting score had a considerably higher risk of poor prognosis than those scoring <2 points (OR 24.35 (1.32; 448), p = 0.03). The weight of pre-existing hypercholesterolemia did not change the risk estimation. Four specific baseline variables, one anamnestic (pre-existing hypercholesterolemia) and three laboratory parameters (leucocyte count, IL-6, and fT3), were significantly associated with poor prognosis as independent risk factors. To prevent adverse outcomes, the updated 4-point score could be useful in identifying at-risk patients, highlighting the need for specific trials to estimate the safety and efficacy of targeted treatments.

Relationship between preoperative FT3 levels and new-onset atrial fibrillation after off-pump coronary artery bypass grafting.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. While thyroid dysfunction can predict POAF, the association between preoperative serum free triiodothyronine (FT3) levels and POAF in patients undergoing off-pump coronary artery bypass (OPCAB) grafting remains unclear. This study aimed to investigate the relationship between preoperative FT3 levels and POAF in OPCAB patients. This prospective observational study included patients with sinus rhythm and no history of atrial fibrillation or thyroid disease who underwent OPCAB and FT3 testing at the Tianjin Chest Hospital from June 2021 to March 2023. The relationship between FT3 level and POAF was evaluated using restricted cubic spline. Cox proportional hazards regression models were used to analyze the associations between FT3 concentration categories [low T3 syndrome (LT3S) (FT3 below the normal range), low normal FT3 (3.10-4.59 pmol/L), high normal FT3 (4.60-6.80 pmol/L)] and POAF, adjusting for potential confounders. Stratified analyses were performed to assess effect modification by gender and age (<60 vs. ≥60 years old). Among 875 patients, 259 (29.6%) developed POAF within 2 days after surgery. Restricted cubic spline analysis showed an S-shaped association between FT3 concentration and POAF risk. Compared to the low normal FT3 group, LT3S was associated with an increased risk of POAF [hazard ratio (HR), 1.41; 95% confidence interval (CI): 1.90-2.19], while high normal FT3 was associated with a decreased risk (HR, 0.72; 95% CI: 0.51-0.99). The association between FT3 and increased POAF risk was more pronounced in patients aged ≥60 years (HR, 1.41; 95% CI: 1.89-2.22). Preoperative FT3 levels most likely could predict POAF risk after OPCAB, especially in patients aged 60 years and older. Measuring FT3 preoperatively may identify high-risk patients benefiting from close monitoring and prophylactic treatment. Further investigation of thyroid hormone replacement therapy for LT3S is warranted.

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.

Abnormal thyroid markers in critically ill patients-harmless irritation or areal problem?

Abnormal thyroid markers are a frequent occurrence in emergency and intensive care medicine. Correct interpretation of their clinical relevance and distinction from a primary thyroid disease, particularly prior to potential administration of iodine-containing antiarrhythmic drugs such as amiodaron or radiocontrast agents, are both essential and challenging. This article aims to present the pathophysiology of abnormal thyroid markers in acute or protracted critical disease. Their relevance for administration of amiodaron or iodine-containing radiocontrast agents is discussed, and concrete practical recommendations are presented. The current work comprises a discussion of expert recommendations, guidelines, and basic research. Approximately one third of intensive care patients develop non-thyroidal illness syndrome (NTIS) during the course of their critical disease. NTIS is characterized by a reduction in the serum concentration of fT3 and, during the course, also in those of thyroid-stimulating hormone (TSH) and fT4, despite an organically intact thyroid gland. A greater extent of the deviations correlates with a worse overall prognosis. The mechanisms involved are manifold and influence different levels of hormonal signaling axes. They are mediated by interaction with acute stress signals such as inflammatory factors and elevated cortisol levels and are influenced by medication. The components vary depending on disease severity and the protracted course. NTIS does not require any specific treatment; the focus is on treating the underlying disease. Latent hyperthyroidism in particular must be distinguished from NTIS. In unclear situations and high-risk constellations, perchlorate is indicated before (and after) iodine exposure.

Towards Personalized TSH Reference Ranges: A Genetic and Population-Based Approach in Three Independent Cohorts.

Background: Serum thyroid-stimulating hormone (TSH) measurement is the diagnostic cornerstone for primary thyroid dysfunction. There is high inter-individual but limited intra-individual variation in TSH concentrations, largely due to genetic factors. The currently used wide population-based reference intervals may lead to inappropriate management decisions. Methods: A polygenic score (PGS) including 59 genetic variants was used to calculate genetically determined TSH reference ranges in a thyroid disease-free cohort (n = 6,834). Its effect on reclassification of diagnoses was investigated when compared to using population-based reference ranges. Next, results were validated in a second independent population-based thyroid disease-free cohort (n = 3,800). Potential clinical implications were assessed in a third independent population-based cohort including individuals without thyroid disease (n = 26,321) as well as individuals on levothyroxine (LT4) treatment (n = 1,132). Results: PGS was a much stronger predictor of individual TSH concentrations than FT4 (total variance in TSH concentrations explained 9.2-11.1% vs. 2.4-2.7%, respectively) or any other nongenetic factor (total variance in TSH concentrations explained 0.2-1.8%). Genetically determined TSH reference ranges differed significantly between PGS quartiles in all cohorts, while the differences in FT4 concentrations were absent or only minor. Up to 24.7-30.1% of individuals, previously classified as having subclinical hypo- and hyperthyroidism when using population-based TSH reference ranges, were reclassified as euthyroid when genetically determined TSH reference ranges were applied. Individuals in the higher PGS quartiles had a higher probability of being prescribed LT4 treatment compared to individuals from the lower PGS quartiles (3.3% in Q1 vs. 5.2% in Q4, Pfor trend =1.7 × 10-8). Conclusions: Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions. As the currently used PGS can only predict approximately 10% of inter-individual variation in TSH concentrations, it should be further improved when more genetic variants determining TSH concentrations are identified in future studies.

Ophthalmic Nanoemulsion Fingolimod Formulation for Topical Application.

Purpose: Fingolimod (FTY720; FT), a structural analog of sphingosine, has potential ocular applications. The goal of this study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. Methods: FT-NE formulations were prepared using homogenization followed by the probe sonication method. The lead FT-NE formulations (0.15% and 0.3% w/v loading), comprising soybean oil as oil and Tween® 80 and Poloxamer 188 as surfactants, were further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. Ocular bioavailability following topical application of FT-NE (0.3%) was examined in Sprague-Dawley rats. Results: The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature postfiltration through a polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release over 24 h, compared with the control FT solution (FT-S). In vivo studies revealed that effective concentrations of FT were achieved in the vitreous humor and retina following topical application of FT-NE. Conclusions: The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

Thyroid function monitoring during pregnancy in euthyroid women with thyroid autoimmunity.

Thyroid autoimmunity (TAI) may be present in 1-17% of pregnant women. Monitoring of thyroid function in euthyroid pregnant women positive for anti-thyroperoxidase antibodies (TPOAb+) is recommended. To determine the prevalence and possible clinical and biological risk factors of biochemical progression (rise in serum thyroid-stimulating hormone (TSH) > 2.5 mU/L) at second blood sampling during pregnancy, in euthyroid women (TSH ≤ 2.5 mU/L) according to their TPOAb status. This study included demographic and biological data from two previously published cohorts (n = 274 women from August 1996 to May 1997 Copenhagen cohort, and n = 66 women from January 2013 to December 2014 Brussels cohort) having at least two measurements of TSH and free thyroxine (FT4) and at least one of TPOAb during spontaneously achieved singleton pregnancies. The majority of women studied did not show biochemical progression. Only 4.2% progressed, significantly more frequently among TPOAb+ women, as compared to TPOAb- group (9.4 vs 2.7%, P = 0.015). No rise in serum TSH > 4 mU/L at 2nd sampling was observed. Higher baseline TSH levels were associated with biochemical progression in both TPOAb+ (P = 0.05) and TPOAb- women (P < 0.001), whereas maternal age, BMI, multiparity, smoking, FT4, and TPOAb concentrations were not significantly different between women with and without progression. Only a minority of euthyroid women with thyroid autoimmunity presented biochemical progression and none with a TSH > 4 mU/L. Larger studies are needed to better target the subset of women who would benefit most from repeated thyroid function monitoring during pregnancy.

Retrospective Cross-Sectional Study of the Relationship of Thyroid Volume and Function with Anthropometric Measurements, Body Composition Analysis Parameters, and the Diagnosis of Metabolic Syndrome in Euthyroid People Aged 18-65.

Background and Objectives: The thyroid is a key endocrine gland for the regulation of metabolic processes. A body composition analysis (BCA) is a valuable complement to the assessment of body mass index, which is derived only from body weight and height. This cross-sectional retrospective study aimed to investigate the relationships between thyroid volume (TV) and thyroid function parameters, anthropometric measurements, BCA parameters, and the presence of metabolic syndrome (MetS) in adults without clinically overt thyroid disease. Material and Methods: This study involved 45 people (females: 57.8%; MetS: 28.9%) hospitalized for planned diagnostics without signs of acute illness or a deterioration of their health and without thyroid disease, who underwent thyroid ultrasound scans, biochemical tests to assess their thyroid function, MetS assessments, anthropometric measurements, and BCAs using the bioelectrical impedance method. Results: The TV was significantly larger in people with MetS compared to people without MetS. The TV was significantly higher and the serum thyrotropin (TSH) concentration was significantly lower in overweight and obese people than in normal and underweight people. The free triiodothyronine (FT3) serum concentration and TV were correlated with waist circumference and some parameters of the BCA, and the FT3 concentration was also correlated with the body mass index, waist-hip ratio, and waist-height ratio. No significant correlations were found between the FT4 and TSH and the results of the anthropometric and BCA measurements. Conclusions: Even in a population of euthyroid patients without clinically overt thyroid disease, there were some significant relationships between the volume and function of the thyroid gland and the results of their anthropometric parameters, BCAs, and the presence of MetS features.

Associations between a normal-range free thyroxine concentration and ovarian reserve in infertile women undergoing treatment via assisted reproductive technology

BackgroundSome recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women.MethodsThis cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12–15.33, 15.34–18.67, and 18.68–22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration < 1.1 ng/mL.ResultsThe average ages of women in the low-normal, middle-normal, and high-normal fT4 tertiles were 33.20 (standard deviation [SD]: 5.11), 32.33 (SD: 5.13), and 31.61 (SD: 5.10) years, respectively (p < 0.0001). AMH concentrations (adjusted mean: 3.32 [95% confidence interval {CI}: 3.16 to 3.50] vs. 3.51 [3.40 to 3.62] vs. 3.64 [3.50 to 3.80] ng/mL, p = 0.022) were significantly different between the fT4 concentration tertiles. The risk of DOR was significantly increased in the low-normal (adjusted odds ratio: 1.61 [95% CI: 1.01 to 2.58]) and middle-normal (1.47 [95% CI: 1.00 to 2.16]) tertiles compared with the high-normal tertile. Subgroup analysis showed that AMH concentrations were significantly different among the fT4 concentration tertiles in women aged < 35 years (adjusted mean: 3.94 [95% CI: 3.70 to 4.20] vs. 4.25 [4.11 to 4.39] vs. 4.38 [4.18 to 4.58], p = 0.028), whereas this difference was not significant in women aged ≥ 35 years (p = 0.534). The general additive models using fT4 as a continuous variable indicated that a lower fT4 concentration within the normal range was significantly associated with a lower AMH concentration (p = 0.027), a lower AFC (p = 0.018), a lower number of aspirated oocytes (p = 0.001), and a higher risk of DOR (p = 0.007).ConclusionLow-normal fT4 concentrations are associated with lower ovarian reserve in infertile women.

CHANGES OF TSH, FT3 AND FT4 LEVELS IN PATIENTS WITH HYPERTHYROIDISM

ntroduction: The thyroid hormone secretion disorders may be hyperthyroidism (reduced TSH levels and increased levels of FT3 and FT4) and subclinical hyperthyroidism (decreased concentration of TSH with normal FT3 and FT4).Aim: To investigate levels of thyroid hormones (TSH, FT3, and FT4) in patients with hyperthyroidism or subclinical hyperthyroidism treated at Tuzla Blue Clinic.Materials and methods:The study included 120 patients divided into three groups: a control group, groups with respondents who have hyperthyroidism, and a group of patients with subclinical hyperthyroidism. The concentrations of the hormones TSH, FT3, and FT4 were analyzed. The determination was carried out on the device IMMULITE 1 Siemens using the immunochemistry method. Results:TSH between our group investigated the existence of significant statistical differences between the control group and the group with hyperthyroidism (p&lt;0.0001) and between the control group and the group withsubclinical hyperthyroidism (p=0.0001), and the parameter FT3 showed that a statistically significant difference exists between the control group and the group with hyperthyroidism (p&lt;0.0001), and between patients with hyperthyroidism andsubclinical hyperthyroidism (p&lt;0.0001). For FT4, we found a statistically significant difference between the control group and the group with hyperthyroidism (p&lt;0.0001) and between groups with hyperthyroidism and subclinical hyperthyroidism (p &lt;0.0001).Conclusions: The concentration of TSH is reduced in both hyperthyroidism and subclinical hyperthyroidism. The serum concentrations of FT3 and FT4 are elevated in hyperthyroidism, while in subclinical hyperthyroidism, the serum concentrations of FT3 and FT4 stand in the reference area.Keywords:Thyrotropin, thyroxine, TSH, FT3, FT4, hyperthyroidism

Thyroid status in patients with early stages of cancer of various localization

Purpose of the study. To determine the thyroid status of primary cancer patients in the early stages of uterine body cancer, kidney cancer, breast cancer, skin melanoma and lung cancer without a history of endocrine pathology.Patients and methods. The content levels of thyroid-stimulating hormone (TSH), thyroid hormones (THs) T4 and T3 of total and free forms were determined in the blood serum by RIA method in 132 patients with breast cancer, uterine body cancer, lung cancer, kidney cancer and skin melanoma (average age 55 years). The comparison group consisted of practically healthy donors.Results. Only in skin melanoma, serum TSH levels were reduced by 1.5 times (p &lt; 0.05). The T4 content was reduced by 1.4–1.7 times (p &lt; 0.05) in uterine body cancer and kidney cancer, increased in lung cancer patients and 16 % of breast cancer patients by 1.4–1.7 times though (p &lt; 0.05). A 1.3–1.5‑fold low (p &lt; 0.05) T3 level was found in breast cancer, kidney cancer, and skin melanoma, while an 1.6‑fold increase (p &lt; 0.05) was found in uterine body cancer. The revealed changes in THs by the type of clinical hyperthyroidism are an increase of 1.8 times (p &lt; 0.05) FT3 on the background of low TSH in the blood in patients with skin melanoma, and by the type of hyperthyroxinemia in patients with lung cancer and breast cancer, consisting in increased concentrations of T4 and FT3, and with free and total T3 levels in patients uterine body cancer, as well as FT4, without changes in TSH in the blood serum of patients, may be associated with the features of malignant pathology, since it is known that THs are proliferation stimulants and can build up in tumors.Conclusion. The development of a malignant tumor even in the early stages of the disease is perceived by the body as a threat for homeostasis and the response to the occurrence of neoplasm is the reaction of the hypothalamicpituitary-thyroid regulatory axis. As an outcome, patients develop euthyroid disorder syndrome.

Concentrations of Bioelements (Zn, Cu, Fe, Cr, Mg, Mn) in Serum and Bone Tissue of Aging Men Undergoing Hip Arthroplasty: Implications for Erectile Dysfunction.

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.

Analysis of Serum Free Thyroxine Concentrations in Healthy Term Neonates Underlines Need for Local and Laboratory-Specific Reference Interval: A Systematic Review and Meta-Analysis of Individual Participant Data.

Background: Initial evaluation of the hypothalamus-pituitary-thyroid axis is done by measuring serum free thyroxine (fT4) and thyrotropin concentrations. For correct interpretation of these measurements, reliable age-specific reference intervals (RIs) are fundamental. Since neonatal fT4 RIs conforming to the Clinical and Laboratory Standards Institute guidelines are not available for all assays, we set out to create literature-based uniform age-specific neonatal fT4 RIs that may be used for every assay. Methods: For meta-analysis of individual participant fT4 concentrations, we systematically searched MEDLINE and Embase (search date December 6, 2023; PROSPERO registration CRD42016041871). We searched for studies reporting fT4 concentrations in healthy term newborns aged 2-27 days, born to mothers without thyroid disease in iodine-sufficient regions. Authors were invited to supply data. Due to standardization differences between assays, data could not be combined for meta-analysis directly, and we attempted to normalize the data using two distinct methods. Results: We obtained 4206 fT4 concentrations from 20 studies that used 13 different assays from 6 manufacturers. First, we set out to normalize fT4 data using the mean and standard deviation of (assay-specific) adult RIs. fT4 concentrations were transformed into Z-scores, assuming a normal distribution. Using a linear mixed-effects model (LMM), we still found a significant difference between fT4 concentration across studies (p < 0.001), after this normalization. As a second approach, we normalized the fT4 concentrations using data from a method/assay comparison study. We used the relationship between the Cobas assay and the other assays as a reference point to convert all values to Cobas values. However, this method also failed to produce consistent results, with significant differences between the normalized data (LMM p < 0.001). Conclusions: We conclude that our attempts at normalizing fT4 assay results were unsuccessful. Confounders related to our unsuccessful analysis may be assay related and/or biological. These findings have significant implications for patient care, since relying on RIs from literature may result in erroneous interpretation of results. Therefore, we strongly recommend to establish local RIs for accurate interpretation of serum fT4 concentrations in neonates.

Correlation between Interleukin-23, Autoantibodies and Thyroid Profile in a Sample of Iraqi Patients with Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis (HT) is the most common autoimmune condition characterized by hypothyroidism and thyroid cell death by leukocytes and antibody-mediated immunological mechanisms. The current paper set out to assess a number of inflammatory and metabolic potential indicators of Hashimoto’s thyroiditis. Fifty-one patients with Hashimoto’s thyroiditis took part in the current investigation. Ages ranged from 20 to 75 for them. Enzyme-linked immunosorbent tests were used to quantify the anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH at the beginning and conclusion of the trial. The result showed a significant relationship between the gender according to HT patient’s and healthy groups which showed that female effected more than male and there was no effected according to the age between these groups, In HT patients with greater TSH concentrations compared to healthy individuals, serum FT3 and FT4 concentrations were lower while IL-23 concentrations were higher. TSH levels were positively correlated with IL-23 levels. As a result, IL-23 can be useful for detecting disease activity in HT patients. However, more thorough, extensive, longitudinal investigations are required to evaluate whether IL-23 can be used in therapeutic settings. Our results showed that thyroid profile, serum IL-23, and autoantibodies were strong indicators of Hashimoto’s thyroiditis. To better understand these correlations and underlying pathogenic mechanisms, additional research is necessary.

Effect of autoantibodies and cytokines on thyroid disorders in Thi-Qar

Introduction: The thyroid gland is one of the important endocrine gland that have many functional activates in the body. It is usually located in the front of the neck and is shaped like a butterfly. It goes all the way down to the platysma, stern thyroid, and Stern hyoid muscles. In all vertebrates, the thyroid gland and its hormones perform several important activities. Methodology: Fifty patients diagnosed with hyperthyroidism disease (25 males and 25 females). 50 subjects in good health as controls (25 males and 25 females). Results and dissuasion: When compared to controls, the findings of our investigation (17.04 ± 5.10 vs. 1.15 ±0.25 U /l) demonstrate a substantial rise (P≥0.00) of TSH-receptor Ab levels in the subjects (17.04 ± 5.10 vs. 1.15 ±0.25 U/l). The findings revealed a substantial rise (P≥0.00) in FT4 level in subjects (6.16 ±0.62 vs. 1.40±0.24 ng/dl) compared to controls. In our investigation, the T3 level demonstrates a considerable rise (P≥0.00) of patients (2.81±0.20 vs. 0.32±0.07 ng/dl) vs. control. The findings of our investigation, which were presented in table 3.2, clearly demonstrated a substantial drop (P≥0.00) of TSH level in subjects was (0.19± 00.6 vs. 3.19± 0.53 IU/L) compared to controls. Conclusions: TSH-R Ab is the better hyperthyroidism marker, especially in individuals having elevated TNF plus IL-6, in both males as well as females. The close relationship among TSH-R Ab elevation, FT-4 as well as FT-3 concentration in patients having hyperthyroidisms, which is associated with increased immune response activity manifested in TNF and IL-6 accompanied by a decrease in the concentration of TSH in general comparisons and between males and females as a control group.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case–control study

BackgroundIt is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3–2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3–4.3 mIU/L). MethodsThis was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n =40), healthy subjects with high-normal target TSH (n =40), subjects with treated hypothyroidism with low-normal target TSH (n =40), and subjects with treated hypothyroidism with high-normal target TSH (n =40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. ResultsSubjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P=0.013). However, serum fT4 levels were found to be significantly different between the study groups (P=0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. ConclusionVariation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

Energy-Related Hormones in Raw and Retail Cow’s Milk and Possible Risk for Consumers

Abstract The study aimed to determine the concentration of energy-related hormones in cow’s milk and to consider them from a public health perspective. Fourteen Holstein cows were subjected to milk and blood sampling on the following days in lactation (DIL): 10, 30, 60, 90, 150, 180, 210, 250 and 280 to determine milk hormones, fat and protein content and blood biochemical parameters. For the same purpose, bulk-tank milk was sampled and samples of retail m ilk with 1.5% (CM1.5) and 3.2% (CM3.2) fat was purchased. Milk insulin-like growth factor-1 (IGF-1) values were significantly lower at 90, 150, 180, 210 and 250 and significantly higher at 10, 30 and 60 DIL than lactation average (LA). Milk insulin concentrations were significantly lower at 30, 60 and 90 and higher at 210, 250 and 280 DIL than LA. Free thyroxine (fT4) level in the milk was higher at 250 DIL, while milk free triiodothyronine (fT3) concentrations were lower at 30, 60, 90 and 280 DIL, and significantly higher at 10 and 180 DIL than respective LA. Milk cortisol levels were lower at 60 and 280 DIL than LA. All measured milk hormones were significantly lower in CM1.5 compared to CM3.2, bulk-tank milk and LA. An exception was the LA of IGF-1, which was significantly lower than the IGF-1 content in CM1.5. Blood biochemical parameters fluctuated evenly during lactation and were within the reference range. Hormone concentrations in cow’s milk fluctuate during lactation, giving milk an important role in the context of public health.

Associations between low muscle mass and clinical characteristics of health population in China

ObjectivesThe primary aim of this study is to discern the association between specific clinical parameters and low muscle mass (LMM). We endeavor to elucidate the determinants of LMM and the predictive potency of individual factors. MethodsIn this retrospective cross-sectional study, we encompassed 450 older adult Chinese participants (252 males and 198 females). Muscle mass quantifications were performed using bioelectrical impedance analysis. Comprehensive data encompassing demographic details (age, sex, height, and weight) and laboratory results (complete blood count, thyroid function, liver function, and renal function) were systematically recorded. Logistic regression models, coupled with receiver operating characteristic curve analytics, were employed to ascertain the variables influencing LMM and to evaluate the predictive validity of each parameter on LMM. ResultsUpon confounding adjustment for age, gender, body mass index (BMI), and free thyroxine (FT4) persisted as a determinant of LMM. Specifically, individuals with an FT4 exceeding 1.105 ng/dL exhibited a 1.803-fold increased propensity for LMM relative to those with FT4 values below the specified threshold. Incorporating age, gender, BMI, and FT4 in the diagnostic algorithm enhanced the precision of LMM. The results differ between men and women. In the male population, we can still observe that FT4 has a certain value in the diagnosis of LMM, but this phenomenon is not found in the female population. ConclusionsElevated FT4 concentrations, albeit within clinically accepted limits, are inversely associated with muscle mass. As such, FT4 could be postulated as a potential biomarker for LMM in geriatric individuals, especially in the male group.

Long-term prognostic value of thyroid hormones in left ventricular noncompaction

PurposeThyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC).MethodsThis longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated.ResultsOver a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313–0.664) and secondary (HR 0.547, 95%CI 0.349–0.858; HR 0.663, 95%CI 0.475–0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance.ConclusionThrough the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.Graphical