FT4 Concentrations Research Articles

IgG4 serum levels in Graves' orbitopathy.

IgG4-related disease (IgG4-RD) can involve many organs, including thyroid and orbital tissues. A link between IgG4, Graves' disease (GD) and Graves' orbitopathy (GO) has been proposed, but results are conflicting. Here we investigated the possible association between IgG4 and GO. Retrospective investigation in 297 patients with Graves' disease (GD), 152 with GO. prevalence of IgG4 ≥ 135mg/dL (cut-off for IgG4-RD). (1) serum IgG4 concentrations; (2) IgG4/IgG ratio; (3) prevalence of IgG4/IgG ratio ≥ 8.0%; (4) relationship between IgG4 and eye features; (5) relationship between IgG4 and anti-TSH receptor antibodies (TRAbs). Because GO patients had lower FT3 concentrations, we evaluated the main objectives in the second and third FT3 quartiles subpopulation, in which there were no relevant differences between patients with (n = 81) or without GO (n = 67) for baseline parameters. Within this population, the prevalence of IgG4 levels ≥ 135mg/dL did not differ between patients without and with GO (17.9% vs 17.3%). No difference was observed concerning IgG4 concentrations, prevalence of IgG4/IgG ≥ 8.0%, and IgG4/IgG ratio. There was no relationship between IgG4 and eye features and no correlation between IgG4 levels and TRAb was found. Our results suggest that, within GD, there is no relationship between serum IgG4 and GO.

Relationship between thyroid function and sex hormones in female German shepherd dogs.

Several variables influence the serum concentration of thyroid hormones in dogs, including breed, age, drugs, and concurrent diseases. However, data regarding the interaction between thyroid function and the estrous stage of female dogs are limited. Estrous stage may influence thyroid function in German Shepherd dogs. Longitudinal, observational, non-randomized cohort study. The dogs were monitored during the complete estrous cycle, and different stages were determined by vaginal cytology. Two blood samples were collected at the beginning and end of each stage to analyze the following: total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3), canine thyrotropin (cTSH), progesterone, 17-β-estradiol, triglycerides, and cholesterol concentrations. Hematological and biochemical evaluations were performed at the beginning and end of the study period. Seventeen German Shepherds were included, of which 7 were bred during the study period. One dog was excluded for estrus interruption and another for suspected hypothyroidism. Serum concentrations of T4, fT4, and fT3 were negatively correlated with age. Total thyroxine demonstrated significant changes in serum concentrations between estrous stages, with higher concentrations in estrus and diestrus. Total thyroxine concentrations were positively correlated with progesterone concentrations and negatively correlated with 17-β-estradiol concentrations. Free thyroxine did not show significant variations but was positively correlated with progesterone concentrations. Canine TSH concentrations were positively correlated with 17-β-estradiol concentrations. No significant differences in thyroid hormones and cTSH concentrations were observed between diestrus during pregnancy and pseudopregnancy. Different stages of estrus can influence the measurement of TT4 in female dogs.

Changes in thyroid function and evolution of subclinical thyroid disease in older men.

Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. Longitudinal study of 994 community-dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow-up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r = .16, p < .05). Change in FT4 correlated inversely with baseline FT4 (r = -0.35, p < .05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully-adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02-1.17, p = .006; per 2.7-fold increase in TSH OR = 65.4, CI = 31.9-134, p < .001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high-normal TSH.

Changes of serum TSH, FT3, and FT4 levels in infants received surgical correction of congenital heart disease under cardiopulmonary bypass

ObjectiveThis study aimed to explore the fluctuations and clinical relevance of serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels in infants undergoing surgical correction for congenital heart disease (CHD) using cardiopulmonary bypass (CPB).MethodsIn a retrospective design, 58 infants who underwent CHD surgical correction under CPB between January 2021 and January 2022 at our institution were incorporated. These infants were categorized into two groups: simple CHD (n = 34) and complex CHD (n = 24). TSH, FT3, and FT4 serum concentrations were assessed at four intervals: 24 h pre-surgery (T0) and 24 h (T1), 48 h (T2), and 72 h (T3) post-surgery.ResultsThe simple CHD group displayed a significantly reduced CPB duration compared to the complex CHD group (P < 0.001). Both groups exhibited a notable decline in serum thyroid hormone concentrations at T1 compared to T0. However, from T1 to T3, an upward trend in hormone levels was observed. By T3, though the levels in both groups had risen notably from T1, they remained significantly diminished from T0 (P < 0.01). In both the simple and complex CHD cohorts, significant fluctuations in thyroid hormone levels (TSH, FT3, FT4) were noted across the different timepoints (T0, T1, T3) (P < 0.01). While no significant disparities were found between the two groups’ hormone concentrations at T0 and T1 (P > 0.05), at T2 and T3, the simple CHD group manifested higher TSH, FT3, and FT4 levels compared to the complex CHD group (P < 0.05).ConclusionsInfants undergoing CHD surgical correction under CPB experience significant declines in TSH, FT3, and FT4 serum levels. The post-surgery thyroid hormone recovery was more pronounced in infants with simple CHD compared to those with complex CHD. As such, vigilant monitoring of thyroid hormone levels during the perioperative phase is imperative, and timely intervention measures should be employed when necessary.

PSVIII-A-4 Evaluation of Blood Parameters Associated to Environmental Stress in Grazing Beef Heifers with Divergent Residual Feed Intake

Abstract There is considerable interest in improved feed efficiency to enhance sustainability in beef production, but a lack of understanding exists on the interaction between residual feed intake (RFI) and environment while grazing. Increasing variation in environmental conditions has been documented in western Canada with summers becoming warmer. This study evaluated blood parameters and rumen temperature (RT) of grazing beef heifers with divergent residual feed intake (RFI) during summer (July to August) of 2022. Forty-four crossbred beef heifers (358 ± 4.78 kg body weight; approximately 14 months of age) previously tested for RFI in drylot and classified as more (n = 21; LOW-RFI = -0.9 ± 0.70) or less feed efficient (n = 23; HIGH-RFI = 1.3 ± 1.00) were grazed at 2.72 AUM/ha over 7 wk in Alberta, Canada. Rumen temperatures were automatically recorded throughout the study using the Smart Rumen Bolus by Moonsyst. Plasma was collected every 14 ± 1 d for 42 d to determine concentrations of blood urea nitrogen (BUN), non-esterified fatty acids (NEFA), insulin-like growth factor 1 (IGF-1), β-Hydroxybutyric acid (BHBA), leptin (LEP), free triiodothyronine (fT3), haptoglobin (HP), heat shock protein 70 (HSP70), and gamma-aminobutyric acid (GABA). Environmental conditions were assessed by calculating the Climate Comprehensive Index using temperature, wind speed, solar radiation, and humidity data from a weather station within 1 km of the grazed pastures. Daily weather conditions were considered to impose risk to cause mild, moderate, severe, and extreme stress for 8, 21, 8, and 1 days, respectively. Plasma and RT data were analyzed as a completely randomized design with repeated measures. An RFI × day interaction was observed for BUN (P = 0.018). LOW-RFI had greater (P = 0.02) BUN on d 42 compared with HIGH-RFI heifers (42.5 vs. 32.6 mg/dL, respectively), while GABA tended to be greater (P ≤ 0.09) for HIGH-RFI heifers on d 0 and 42. Free T3 concentrations were greater (P = 0.04; 8.54 vs. 7.78 pmol/L, respectively), whereas HP was less (P = 0.01) in LOW-RFI heifers. However, HP concentrations were below the threshold for inflammation throughout the study. There was also an effect of day (P &amp;lt; 0.01) for fT3, IGF-1, LEP, NEFA, HSP70, and BHBA. Leptin and HSP70 concentrations were greatest on d 14 and 28, whereas BHBA was the greatest (P &amp;lt; 0.01) and IGF-1 the least on d 42 (P &amp;lt; 0.01). An RFI × hour interaction was detected for RT (P = 0.0003), where HIGH-RFI heifers had greater RT throughout the day. In summary, weather conditions in western Canada changed blood parameters of replacement beef heifers during summer. Feed efficient heifers had decreased RT and greater plasma concentrations of fT3, which could be associated with metabolic homeostasis and regulation of thermogenesis.

The effect of metformin therapy on serum thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis

Type 2 diabetes and thyroid function disorders are two common chronic endocrine disorders with the high prevalence in various populations. Metformin is well established as the first-line drug therapy for managing diabetes mellitus. In this meta-analysis, we aimed to determine the effect of metformin on serum TSH and FT4 concentrations in patients with type 2 diabetes. We searched PubMed, Scopus, web of science, Cochrane library, and google scholar to collect information on the effect of metformin on serum TSH and FT4 levels. Demographic and clinical information and serum TSH and FT4 concentrations before and after metformin treatment were extracted. Studies on patients over 18 years of age were included. A total of 11 studies including 1147 patients were selected for the final analysis. In hypothyroid patients, the TSH level decreased significantly after treatment with metformin (Hedges’s g:1.55, 95%CI 0.93–2.16, p-value < 0.001); FT4 level increased slightly after taking metformin, but the increase was not significant (Heddges’s g: − 0.30, 95%CI − 0.90,0.31, p-value = 0.34). In euthyroid subjects, the slight decrease found in TSH and FT4 concentrations was not statistically significant. Metformin reduces TSH levels in hypothyroid patients; however, it has no effect on TSH levels in euthyroid patients. Metformin does not affect serum FT4 levels in euthyroid and hypothyroid patients.

Hyperthyroidism: A Review.

Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

Large method differences for free thyroid hormone assays in the hyperthyroid range can affect assessment of hyperthyroid status: Comparison of Abbott Alinity to Roche Cobas, Siemens Centaur and equilibrium dialysis LC-MS/MS

BackgroundFree T4 (FT4) determination is one of the most commonly performed biochemical tests in endocrinology. Treatment of thyroid dysfunctions is adjusted based on the severity of symptoms and biochemical test results. For Graves’ hyperthyroidism, clinical guidelines recommend using FT4 as a (rough) guide to dose antithyroid drugs, together with other clinical information. It is well known that different platforms and methods give different FT4 results; however, large non-linear method differences at high FT4 concentrations are less well recognized. Current clinical guidelines do not make it clear that method differences in the hyperthyroid range can affect recommendations. MethodSerum samples from patients with very low (biochemically hypothyroid) to very high (hyperthyroid) concentrations of FT4 and/or free T3 (FT3) were analyzed using Abbott Alinity and compared to concentrations measured using Roche Cobas, Siemens ADVIA Centaur (FT4 only) and an in-house equilibrium dialysis liquid chromatography tandem mass spectrometry (LC-MS/MS) method. ResultsAlinity measured markedly lower FT4 and FT3 concentrations compared to the other methods, particularly at high FT4 concentrations. Regression analysis indicated that Alinity FT4 had a non-linear (curved) relationship to FT4 measured by the other methods. The method differences affected guideline-recommended treatments for hyperthyroidism. ConclusionMeasured free thyroid hormone concentrations are highly method-dependent, especially at high FT4 concentrations. Clinicians treating hyperthyroid patients should be aware that patients appear much less hyperthyroid from FT4-measurements performed using Alinity compared to Cobas or Centaur. Guideline-recommended antithyroid drug dosages based on FT4 (including multiples of the upper reference range) have to be adjusted to the FT4 method used. FT4 results from different methods should be clearly distinguished (e.g. separate lines) in medical records.

Effects of the abdominal fat distribution on the relationship between exposure to air pollutants and thyroid hormones among Korean adult males

BackgroundSeveral significant associations between air pollution and thyroid function have been reported, but few studies have identified whether these associations differ by obesity, particularly its regional distribution. We assessed the relationship between ambient air pollution and thyroid hormone, and whether this relationship is modified by abdominal adiposity, as indicated by the waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral-to-subcutaneous fat ratio (VSR) in Korean men.MethodsWe included 2440 male adults in the final analysis and used each person’s annual average exposure to four air pollutants: particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). Abdominal fat deposition was quantified by computed tomography. Serum thyrotropin (TSH) and free thyroxine (FT4) concentrations were measured for thyroid hormone. To evaluate the relationship between air pollution and thyroid hormone according to adiposity, we performed multiple linear regression analysis on the two subgroups stratified by abdominal fat level.ResultsAbdominal adiposity was significantly related to FT4 concentration. The exposures to air pollutants were associated with increased TSH and decreased FT4 concentrations. In stratified analysis using abdominal fat traits, ambient air pollution except for SO2 was significantly related to increased TSH and decreased FT4 concentrations in the high adiposity group (all p < 0.05), but not in the normal adiposity group. Among the air pollutants, PM10 showed an association with an increase of TSH concentration in all group with high adiposity, including high VAT, high SAT, and high VSR groups (all p < 0.05). In case of FT4, CO showed a similar pattern. Among the abdominal fat-related traits, the VSR in the high adiposity group had the largest effect on the relationship between exposure to air pollutants and thyroid hormone.ConclusionsThis study suggests the first clue that the relationship between air pollution exposure and thyroid hormone differs according to abdominal fat distribution among Korean adult males.

FRI491 The Impact Of Insulin Resistance On Thyroid Function In Pregnancy

Abstract Disclosure: M. Trofimiuk-Muldner: None. A.J. Nowak: None. J. Podlewski: None. A. Hubalewska-Dydejczyk: None. The influence of hyperinsulinemia on thyroid function is debatable. Insulin as an anabolic hormone may be responsible for thyroid hypertrophy and nodular development. The interplay between insulin and the function of the pituitary-thyroid axis may influence thyroid tests’ results and their interpretation. This study evaluated the association between thyroid hormones and insulin resistance in pregnant women. The study group was recruited from the Polish National Program for Elimination of Iodine Deficiency, conducted between 2007-2017. We assessed the fasting glucose, insulin levels, thyroid hormones (TSH, FT4, FT3), and ATPO antibodies in 1069 pregnant women (median age 29 years, IQR 6 years). Based on calculated HOMA-IR, participants were stratified into three subgroups HOMA1 (324 women with HOMA-IR &amp;lt; 1), HOMA 2 (570 women with HOMA-IR ≥1&amp; &amp;lt;2.5) and HOMA3 (175 women with HOMA-IR ≥ 2.5). Results: Median (IQR) TSH concentrations were 1.42 (1.33) mIU/L, 1.65 (1.31) mIU/L, and 1.77 (1.29) mIU/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) FT4 concentrations were 12.9 (3.0) pmol/L, 12.48 (2.85) pmol/L, and 11.38 (2.8) pmol/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) FT3 concentrations were 4.79 (1.75) pmol/L, 4.6 (1.02) pmol/L, and 4.47 (0.88) pmol/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) aTPO concentrations were 10 (11.34) IU/L, 11.59 (8.54) IU/L, and 10.15 (7.5) mIU/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. HOMA1 and HOMA2 subgroups differed significantly in TSH (p=0.026) and FT3concentrations (p=0.001). HOMA2 and HOMA3 subgroups differed significantly in FT4 (p&amp;lt;0.001) and aTPO concentrations (p=0.045). HOMA1 and HOMA3 patients differed in TSH (p=0.001), FT4 (p&amp;lt;0.001), and FT3 (p=0.001) concentrations. aTPO-positivity was not related to HOMA-IR values (mean HOMA-IR in aTPO-positive andaTPO-negative women were 1.63 and 1.80 respectively, p=0.32). Conclusions: Insulin resistance may impact thyroid function in pregnancy independently of thyroid autoimmunity, with higher TSH and lower thyroid hormones concentrations in pregnant women with higher HOMA-IR indices. Presentation: Friday, June 16, 2023

OR26-06 Cardiovascular Morbidity And Mortality In Patients With Resistance to THYROID Hormone (RTH): A Linked Record Study

Abstract Disclosure: O. Okosieme: None. D. Usman: None. P. Taylor: None. C. Dayan: None. G. Lyons: None. C.M. Moran: None. V.K. Chatterjee: None. A. Rees: None. Introduction: Individuals with Resistance to Thyroid Hormone β (RTH-β) may develop cardiac disease, including cardiomyopathy or arrhythmia. Long-term survival outcomes in this group of patients have not been systematically evaluated. Objectives: We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTH-β in endocrine clinics in Wales. Methods: In a retrospective cohort study using linked datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank, Welsh patients with genetically-proven RTH-β were identified from laboratory records (n=55), matched to population controls by age and sex (n=2750), and linked to outcomes in SAIL. We used Kaplan-Meier and Cox regression models to analyse the association of RTH-β with all-cause mortality, acute myocardial infarction, atrial fibrillation, heart failure, strokes and major adverse cardiovascular events (MACE; a composite of cardiovascular death, acute myocardial infarction, heart failure, and strokes). We also investigated any association between baseline thyroid hormone concentrations and outcomes using restricted cubic splines. Results: Compared to controls, patients had an increased risk of all-cause mortality (Hazard ratio [HR] 2.84, 95% Confidence Interval [95%CI] 1.59-5.08), MACE (HR 3.49, 95%CI 2.04-5.99), atrial fibrillation (HR 10.56, 95%CI 4.72-23.63), and heart failure (HR 6.35, 95%CI 2.26-17.86). Positive associations between FT4 concentration at diagnosis and subsequent cardiovascular morbidity or death were observed, with a 7% increased risk of death per pmol/L increase in FT4. The relationship between FT4 and outcomes was non-linear, with increased risk associated with FT4 concentration exceeding 30 pmol/L. When compared to no intervention, treatment with antithyroid drugs, radioiodine/surgical ablation or levothyroxine, alone or in combination, did not effectively control thyroid hormone excess in the long-term. Conclusion: Patients with RTH-β have increased mortality and cardiovascular outcomes that correlates with high, circulating thyroid hormone levels. Ideal future therapies would target both thyroid hormone excess and tissue resistance and could potentially reduce cardiovascular risk in this disorder. Presentation: Saturday, June 17, 2023

FRI485 High Interlaboratory Variability In Free Thyroxine Measurement Indicates Need For Method Standardization

Abstract Disclosure: A. Ribera: None. U. Danilenko: None. O. Sugahara: None. L. Collins: None. T. Buchannan: None. N. Vazquez: None. F. Pokuah: None. D. Wirtz: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None. Thyroid function tests are critical to diagnose diseases of the thyroid. Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. In response to these concerns, the CDC Clinical Standardization Program (CSP) has created a standardization program for FT4 based on the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system and is partnering with IFCC to standardize FT4 and harmonize TSH testing globally. As part of this program, CDC developed an accurate and sensitive reference measurement procedure (RMP) to assign reference values to individual donor sera. Assay manufacturers and research and clinical laboratories can use these sera to assess the analytical performance of their measurements, and monitor analytical performance over time. To obtain initial information about the analytical performance of FT4 and TSH measurements, an interlaboratory study among commercial assays and laboratory developed test was conducted. A panel of 40 blinded, fresh-frozen single donor patient serum samples with FT4 concentration ranging between 11-32 pmol/L concentrations was measured by participants and compared to the results obtained by CDC RMP for FT4. In addition, commercial assay manufacturers were asked to measure thyroid-stimulating hormone (TSH). Results from sixteen commercial assays and four laboratory developed test (LDT) participated. Preliminary results indicate a negative mean bias for all commercial FT4 assays ranging from -34.46% to -5.08%. Some of the assays agreed more closely to the RMP than others (four assays had mean bias over -25%). An equilibrium dialysis mass spectrometry-based assays had mean biases ranging from -8.86% to - 1.72% agreeing well with RMP. The data suggest that the observed bias can be effectively minimized through recalibration to the RMPs operated by the CDC CSP and the IFCC reference laboratory network. The mean TSH concentrations ranged from 0.34 to 21.56 uIU/mL with mean %CV of 11.42% (95%CI 8.07%-14.76%) suggesting good agreement between various platforms. Findings from this study will be used to customize CDC’s protocols and procedures for standardizing FT4 measurements. Presentation: Friday, June 16, 2023

Thyroid-Related Hormones Changes Predict Changes in Anthropometric Measures and Incidence of Obesity in Chinese Euthyroid Persons.

The purpose of this study was to investigate the correlation of thyroid-related hormones changes within the reference range with the changes in anthropometric measures and incidence of obesity. The study included 4850 subjects with normal thyroid-related hormones at baseline and at follow-up. We evaluated the relationship of changes in thyroid-related biomarkers with anthropometric measures changes and incidence of obesity. In euthyroid persons, changes in serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) concentrations and FT3/FT4 ratio were independent predictors of changes in body mass index (BMI) and waist circumference (WC) in men, changes in serum FT3 and FT4 concentrations and FT3/FT4 ratio were independent predictors of changes in BMI and WC in women. Every single unit increment in ΔFT3/FT4 was accompanied by a 7.144 and 7.572 times risk of having obesity in men and women, respectively. Every single unit decrement in ΔFT4 was accompanied by a 21.0% and 26.9% lower risk of having obesity in men and women, respectively. In conclusion, in euthyroid individuals, changes in thyroid-related hormones were associated with anthropometric measures changes and incidence of obesity.

A-059 Evaluation of Free Thyroxin Levels in Patients with Low Thyroxin Binding Globulin Concentrations: Is There Interference in the FT4 Indirect Method?

Abstract Background Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in serum. Variations in the serum concentration of TBG determine proportional variations in the total serum concentrations of T4 and T3, without implying changes in function, as long as the free fraction remains normal. Several common clinical conditions lead to significant alterations in TBG levels, the most important factor behind low levels being genetic defects. As TBG is encoded by a gene located on the X chromosome, the defects are more easily manifested in males. Differences in FT4 concentrations were observed in sera from subjects with TBG abnormalities, when FT4 are measured by different immunoassays, specially at extremes of TBG concentrations. The objective of this study was to evaluate FT4 levels by indirect method in patients with low TBG concentrations. Methods We analyzed blood samples requesting serum TBG, TSH and FT4 levels from patients admitted to a private reference clinical laboratory in Brazil, from January 01, 2017 to December 31, 2022. Anonymized data on laboratory tests was available from a database of the local Laboratory Information System. All the patients included had TSH within the reference range, 0.4–4.3 mUI/mL (ECLIA, Modular, Roche). FT4 was measured by ECLIA (0.7–1.8 ng/dL) and TBG by ICMA, Immulite, Siemens, 13–39 mcg/mL. Results 357 patients with low TBG levels were evaluated, 220 (62%) men, 137 (38%) women; mean age 35 yrs (19 d to 88 yrs). They were divided in six groups according TBG levels (mcg/mL): &amp;lt;3.5–17 (M 15, F2); 3.5 to 6.0 - 26 (M 20, F 6); 6.1 to 8.0 - 30 (M 25, F 5); 8.1 to 9.9 - 59 ( M 32, F 27); 10.0 to 11.9 - 139 (M 78, F 61); 12.0 to 12.9 - 86 (M 50, F 36). Three patients had FT4 levels above 1.8 (1.85; 1.87 and 1.96) ng/mL, all them male, with TBG levels &amp;lt;3.5; 5.79 and 9.53 ng/mL, respectively. Conclusion FT4 Indirect methods are developed taking into account the presence, in the serum, of a thyroxine binding capacity within the normal range, a fact that does not occur in individuals with extreme TBG deficiency. In this study, we found only one slightly elevated FT4 value among 17 patients with TBG values below 3.5 mcg/mL, suggesting little interference of very low TBG levels in this indirect free T4 method.

A-032 Comparative Serum Free Thyroxine Measurements between Immunoassays and ID-LC/MS/MS Procedure Based on Equilibrium Dialysis

Abstract Background Serum free thyroxine (FT4) measurement is one of the most important clinical laboratory tests for diagnosis and classification of thyroid disorders. Currently serum FT4 is commonly measured with Immunoassays (IAs) in patient care. However, there are concerns about the accuracy of FT4 IAs. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for standardization of routine FT4 IAs. As FT4 RMP is not intended for routine clinical application, in the current study, we aim to develop a high-throughput routine FT4 method based on ED-isotope dilution liquid chromatography tandem mass spectrometry (ED-ID-LC/MS/MS). FT4 RMP was used as a reference to evaluate the measurement accuracy of our ED-ID-LC/MS/MS method and an IA method, respectively. Methods FT4 in dialysate was isolated from protein-bound T4 in serum by using a commercially available micro-ED plate after 18-h ED. The 13C6 labeled T4 was added into dialysate as an internal standard. FT4 in dialysate was purified with 96-well C18 SPE plate. FT4 in the dialysate samples was analyzed by using LC/MS/MS. The T4 certified primary reference material (IRMM-468) was used for assay calibration. FT4 IA measurement was conducted in clinical analyzers (Roche e411). A set of 40 single donor sera, covering a FT4 concentration range of 11.2–32.1 pmol/L were measured by IA and our ED-ID-LC/MS/MS, respectively. Deming regression analysis was performed to compare the results obtained by these two methods with the reference values assigned by FT4 RMP. Results The described high-throughput method based on ED-ID-LC/MS/MS could simultaneously quantified T4, T3, reverse triiodothyronine (rT3) in the dialysate within 4.5 min. The linear range of the routine FT4 assay covered 1–100 pg/mL. The assay sensitivity allowed detection of 0.3 pg/mL FT4 in serum, which is sufficient for FT4 measurement in clinically relevant ranges including hypothyroid patient samples. The throughput of the ED-ID-LC/MS/MS method could be further improved by application of automated liquid handling system. Deming regression analysis showed good agreement between RMP and the routine ED-ID-LC/MS/MS method with a slope close to 1 (P &amp;gt; 0.05) and an intercept close to 0 (P &amp;gt; 0.05), indicating that the results generated from the platform of high-throughput ED-ID-LC/MS/MS could be tracible to FT4 RMP. However, proportional bias (P &amp;lt; 0.05) with slope of 0.74 and constant bias (P &amp;lt; 0.05) with intercept of 2.6 was observed between RMP and IA tested, indicating calibration bias should be addressed to standardize IA. Conclusion In summary, the accuracy, sensitivity, and throughput of ED-ID-LC/MS/MS method are appropriate for FT4 measurements in clinical laboratories and in large epidemiologic studies to establish accurate reference intervals for FT4. Population data generated by FT4 ED-ID-LC/MS/MS method will support the use of standardized FT4 measurements.

A-080 Overcoming Challenges of Equilibrium Dialysis-Based Free Thyroxine Measurements

Abstract Background Thyroid function tests are widely used to detect diseases of the thyroid. Concerns about the accuracy and reliability of free thyroxine (FT4) measurements have been stated by the clinical laboratory community. To address these concerns, CDC established a reference measurement procedure (RMP) for FT4 based on equilibrium dialysis (ED). ED-based methods have advantages over traditional direct immunoassays. As with all analytical methods, factors affecting accuracy and reliability of ED-based methods need identification and understanding. To investigate potential sources of error, the CDC FT4 RMP was used to evaluate T4 stability at different of storage conditions, adsorption of FT4 to common labware surfaces, and the effect of dialysis membrane materials on the measured FT4 in serum. Methods FT4 was measured in serum using the IFCC RMP (1). FT4 was separated from the protein-bound form during the equilibrium dialysis step of the RMP. Dialysates were spiked with internal standard (13C6-T4) and the analyte was further isolated by C18 solid phase extraction (SPE) and liquid-liquid extraction (LLE) in ethyl acetate prior to injection on an UHPLC system coupled with a triple quadrupole mass spectrometer. Bracketed calibration and primary reference materials were used to determine FT4 concentration in serum. This procedure was used to evaluate stability of serum FT4 during storage at −70 to 5 °C. Short- and long-term T4 stability of calibrator solutions at −70 °C to ambient temperature and the extent of adsorption of T4 calibrator solutions to the commonly used labware surfaces were evaluated. Furthermore, the suitability of 4 different dialysis membranes was assessed. In addition, three alternatives to the currently used SPE and LLE extraction steps were tested: LLE using cyclohexane and ethyl acetate, LLE with ethyl acetate, and supported liquid extraction with cyclohexane and ethyl acetate. Results T4 calibrator solution was stable in 1.7% ammonium hydroxide in ethanol for at least 2.9 years at −70 °C and up to 7 days at ambient temperature. Exposure of various calibrator solutions such as T4 in ethanol, ethanol with 1.7% ammonium hydroxide, 10% acetonitrile with 0.1% formic acid to common labware resulted in up to 10.1% loss of the analyte. FT4 in serum and T4 in dialysates and extracts were stable at −70 to 5 °C. Use of alternative dialysis membranes resulted in up to −8.8% mean bias to the reference membranes. Recoveries of the analyte using four extraction methods were 85.4%–95.0%. None of the tested extraction conditions significantly changed the results obtained with the original FT4 RMPs. Conclusion Although FT4 RMP must strictly adhere to the ED conditions described for the RMP, other parts of the sample preparation procedures can deviate from the originally published procedure. Careful selection of procedure for calibrator solvents, dialysis membranes, labware, and storage conditions is required to ensure accurate and reproducible FT4 measurements.

The effects of common genetic variation in 96 genes involved in thyroid hormone regulation on TSH and FT4 concentrations

The effects of common genetic variation in 96 genes involved in thyroid hormone regulation on TSH and FT4 concentrations

Clinical and thyroid profile in patients with COVID-19 hospitalized in an intensive care unit.

This study aimed to summarize the epidemiological and clinical features of thyroid function in COVID-19 patients in the intensive care unit (ICU) of Civil Fray Antonio Alcalde Hospital in Mexico. This is a cross-sectional study that included 63 ICU patients with COVID-19 from August 2021 to December 2021. Thyroid function was evaluated through the TSH, T4, T3, and FT3 measures. Comorbidities such as diabetes mellitus type 2 (T2DM), arterial hypertension (HT), body mass index (BMI), and biochemical biomarkers, including procalcitonin (PCT) and C reactive protein (CRP), were also analyzed. A total of 63 patients with COVID-19 were hospitalized in the ICU; 42 (67%) were male, and 21 (33%) were female, with a mean age of 47 (range of 26-76 years). A total of 49 (78%) patients were non-vaccinated, 5 (8%) had an incomplete vaccination schedule, and 4 (6%) had completed the vaccination schedule. Regarding BMI, 10 (16%) were overweight, and 26 (40%) reported obesity. When assessing thyroid function, 8 (13%) patients were euthyroid, and 55 (87%) showed alterations on the thyroid hormonal axis, mainly a low concentration of TSH (0.56±0.79; p=0.0001) and FT3 (2.34±0.52; p=0.0006). In addition, increased PCT concentrations were associated with a higher risk to decease (1.22 vs. 8.21; p=0.0001) in this group of patients. Based on our findings, it appears that COVID-19 patients with low TSH and FT3 levels, who have not been vaccinated against SARS-CoV-2, are overweight or obese, and exhibit high levels of PCT are more likely to experience a poor prognosis and even mortality.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial

BackgroundUnderstanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients.MethodsRadioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 μg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 − 24 were calculated at the last visit.ResultsSerum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 − 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group.ConclusionCombined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested.IRCT registration numberIRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13. Registration date: 08/12/2021.

Characteristics of euthyroid sick syndrome in patients with breast cancer

Purpose. Determination of thyroid hormones (TH) and cortisol levels in blood in patients with breast cancer (BC) without previously detected endocrine pathology in the anamnesis.Patients and methods. Twenty-five primary luminal A breast cancer patients before and aſter surgical removal of the tumour and 25 breast cancer patients with secondary metastatic brain lesions were examined. The levels of total and free forms of TH (T4, FT4, T3 FT3) and cortisol were determined in serum by RIA method.Results. Before treatment in all patients with breast cancer the level of T3 was decreased 1.3 times and FT3 was increased 1.3 times (p &lt; 0.05) against the background of normal TTH content. In 80 % of patients, blood cortisol concentration was 2 times higher than normal, and in 16 % of patients, T4 level was 1.8 times higher than normal (p &lt; 0.05). Aſter tumour removal, FT3 levels in all patients and cortisol levels in 40 % of patients did not differ from normal. T4 content in 40 % of patients, and T3 and TTH in 28 % of women were above normal. A distinctive feature of patients with brain metastases of breast cancer was low T4 and cortisol levels in 36 % of patients against the background of low T3 levels.Conclusions. Euthyroid sick syndrome was detected in all patients with BC: low serum T3 levels against the background of normal serum levels of TTH. Patients with primary BC were characterized by high concentrations of FT3 and cortisol, which could promote proliferation of malignant cells and decrease antitumour immunity. The condition of 1/3 of patients with brain metastases was aggravated by low levels of T4 and cortisol which could indicate the depletion of the main regulatory systems and an unfavorable disease prognosis.