Measurement Of Thyroxine Research Articles

Development of an equilibrium dialysis ID-UPLC-MS/MS candidate reference measurement procedure for free thyroxine in human serum

BackgroundAccurate and reliable measurement of human serum free thyroxine (FT4) is critical for the diagnosis and treatment of thyroid diseases. However, concerns have been raised regarding the performance of FT4 measurements in patient care. Centers for Disease Control and Prevention Clinical Standardization Programs (CDC-CSP) address these concerns by creating a FT4 standardization program to standardize FT4 measurements. The study aims to develop a highly accurate and precise candidate Reference Measurement Procedure (cRMP), as one key component of CDC-CSP, for standardization of FT4 measurements. MethodsSerum FT4 was separated from protein-bound thyroxine with equilibrium dialysis (ED) following the recommended conditions in the Clinical and Laboratory Standards Institute C45-A guideline and the published RMP [20,21,23]. FT4 in dialysate was directly quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization. Gravimetric measurements of specimens and calibrator solutions, calibrator bracketing, isotope dilution, enhanced chromatographic resolution, and T4 specific mass transitions were used to ensure the accuracy, precision, and specificity of the cRMP. ResultsThe described cRMP agreed well with the established RMP and two other cRMPs in an interlaboratory comparison study. The mean biases of each method to the overall laboratory mean were within ±2.5%. The intra-day, inter-day, and total imprecision for the cRMP were within 4.4%. The limit of detection was 0.90 pmol/L, which was sufficiently sensitive to determine FT4 for patients with hypothyroidism. The structural analogs of T4 and endogenous components in dialysate did not interfere with the measurements. ConclusionOur ED-LC-MS/MS cRMP provides high accuracy, precision, specificity, and sensitivity for FT4 measurement. The cRMP can serve as a higher-order standard for establishing measurement traceability and provide an accuracy base for the standardization of FT4 assays.

In situ characterization of human fingernails by optical front-face fluorescence for the identification of primary hypothyroidism

Primary hypothyroidism is classified as a public health issue by the World Health Organization. The technique for diagnosing hypothyroidism is the measurement of thyroid stimulating hormone (TSH) and thyroxine (FT4). It is necessary to develop new methods that are more accessible, especially for developing countries. The aim of this work is the in-situ use of nail fluorescence for a simple and rapid preliminary diagnosis of primary hypothyroidism. The choice of the nail as biological tissue is justified because nails have a long-term memory, act as a mirror of health, and serve as an early warning system as well as a window of systemic disease. The in situ analysis of the nails of the patients shows good results. Specially, a clear separation was obtained between healthy controls and patients and also between low- and high-level hypothyroidism. Moreover, a strong correlation between fluorescence spectra and TSH values for the population with hypothyroidism was clearly established. Moreover, linear discriminant analysis shows that it is possible to predict the state of test patients after the training of a fraction of the population.

Challenges in Thyroid Function Testing: Interferences and Clinical Implications

In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry. The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions. Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism. The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands. Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention. Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome. In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.

PS-B04-3: SHORT-TERM LOW IODINE DIET EXACERBATES VASCULAR REACTIVITY WITHOUT ALTERING THYROID HORMONE PROFILES IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: Iodine is an essential microelement required for thyroid hormone (TH) synthesis and regulation. Recent evidence links iodine to direct cardiovascular functional changes independent of TH. We aimed to determine the short-term effect of a low iodine diet on cardiovascular parameters in young Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats. Design and method: 5-week-old WKY and SHRSP males and females (n = 5–7 per group) were assigned a normal (NID) or low iodine (LID) diet for 4 weeks. Iodine content was 1.2 mg/kg for NID and 0.211 mg/kg for LID. Tail cuff blood pressure (BP) and body weight were measured pre-diet and weekly. Transthoracic echocardiography, food intake, water consumption, and urine production were determined pre-diet and fortnightly. At sacrifice, thyroid tissue was weighed and snap-frozen for sodium iodide symporter (NIS) gene expression. Plasma was collected for thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) measurement. Third-order mesenteric arteries were assessed for vascular function using wire myography. Results: Baseline TSH, fT3, and fT4 levels were not significantly different between strains. LID did not influence food intake, body weight, thyroid weight, left ventricular (LV) mass, relative wall thickness (RWT) or BP. TSH levels, but not fT3 or fT4, significantly increased by 63.3% in SHRSP males (p = 0.0002) and 74.5% in females fed LID (p = 0.018) but not in WKY when compared to strain, sex- and age-matched rats fed NID. NIS expression significantly increased by 3.27-fold in WKY males fed LID when compared to WKY males fed NID (p = 0.03) but not in SHRSP males. A similar trend in NIS expression was observed in WKY females fed LID. Water intake/urine output ratio significantly increased by 53.62% in SHRSP females fed LID compared to SHRSP females fed NID (p = 0.04). Trends towards reduced stroke volume (SV) and cardiac output (CO) were observed in males fed LID compared to those fed NID irrespective of strain. Vascular reactivity to U46619 in third-order mesenteric resistance arteries was significantly increased by 24.9% in SHRSP males fed LID compared to SHRSP males fed NID (p = 0.03). A similar trend was evident in SHRSP females fed LID when compared to SHRSP females fed NID. Conclusions: Our results demonstrate that short-term LID increases vascular reactivity in SHRSP male rats and is associated with altered expression of genes that encode iodine transport proteins yet independent of thyroid hormone levels.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS.The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism.Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Cut-offs for thyroid peroxidase and thyroglobulin antibodies in early pregnancy.

Thyroid disease in women of reproductive age is mainly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers. Adding to this, much focus in pregnancy is on euthyroid women who are thyroid antibody positive. Evidence to substantiate the cut-offs for the definition of thyroid autoantibody positivity in early pregnant women is warranted. Stored serum samples from 14,030 Danish pregnant women were used for the measurement of TPO-Ab, Tg-Ab, TSH, and free thyroxine (ADVIA Centaur XPT, Siemens Healthineers). Among all women, a reference cohort of 10,905 individuals was identified for the establishment of antibody cut-offs. Percentile cut-offs for TPO-Ab and Tg-Ab were determined using regression on order statistics (the reference cohort). The established cut-offs were then applied (the full cohort), and frequencies of early pregnancy as well as later diagnosis of hypothyroidism were evaluated. The highest established cut-offs (95th, 97.5th, and 99th percentiles) were 59, 68, and 81 U/mL for TPO-Ab and 33, 41, and 52 U/mL for Tg-Ab. When the cut-offs were applied in the full cohort, 11.0, 10.2, and 9.7% were TPO-Ab positive, whereas 13.3, 12.3, and 11.2% were Tg-Ab positive. Antibody-positive women (TPO-Ab and/or Tg-Ab) had higher median TSH and were more likely to have hypothyroidism in early pregnancy and to be diagnosed with hypothyroidism during follow-up. This large study established and evaluated pregnancy-specific cut-offs for TPO-Ab and Tg-Ab. The findings are important regarding the classification of exposure in pregnancy and assessment of thyroid autoimmunity per se.

Pregnancy disrupts the accuracy of automated fT4 immunoassays.

Thyroid hormone measurements are often performed in pregnant women, as hypo- and hyperthyroidism during pregnancy can severely affect the fetus. Serum free thyroxine (fT4) measurements are well known for their analytical challenges, due to low serum concentrations and the subtle equilibrium between free and bound T4 (to thyroid-binding globulin (TBG), transthyretin and albumin). Pregnant women have high TBG concentrations due to an increase in human chorionic gonadotropin (hCG) and estrogen and lower albumin concentrations which change the equilibrium and may affect the validity of fT4 measurements in their samples. As accurate serum fT4 measurements in pregnant women are important for the long-term health of the fetus, we aimed to evaluate the accuracy of several fT4 immunoassays in the serum of pregnant women. FT4 was measured in healthy controls and pregnant women using a candidate-reference method (LC-MS/MS) and five commercially available automated immunoassays (Alinity (Abbott), Atellica (Siemens), Cobas (Roche), Lumipulse (Fujirebio) and UniCel DXI (Beckman Coulter)). Method comparisons (Bland Altman plots and Passing and Bablok analyses) were performed. Serum samples from both healthy controls (n = 30) and pregnant women (n = 30; mean gestational age, 24.8 weeks) were collected. The fT4 immunoassays deviated +7 to +29% more from the LC-MS/MS in serum samples of pregnant women than healthy controls (falsely high). Our results indicate that immunoassays overestimate fT4 in pregnant women, which might lead to an overestimation of thyroid status. Physicians and laboratory specialists should be aware of this phenomenon to avoid drawing false conclusions about thyroid function in pregnant women.

ODP479 Equilibrium Dialysis ID-LC/MS/MS Procedure for Routine Measurement of Free Thyroxine in Serum

Abstract Free thyroxine (FT4) test is essential for diagnosis of thyroid diseases. Most FT4 tests used in patient care are immunoassays (IAs). However, concerns about the accuracy of FT4 IAs have been raised in the clinical laboratory community. Reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established and are well recognized. While FT4 RMP is highly accurate and precise, it is not intended for routine clinical use. Our aim is to develop an ED-based FT4 assay that is traceable to the RMP and suitable for routine measurements such as investigations in epidemiologic studies. The described assay is based on ED-LC-MS/MS. FT4 in serum was isolated from protein-bound T4 in serum according to the CLSI C45-A guideline. FT4 levels achieved equilibrium in a commercially available micro-ED plate after 18 hours. The dialysate was collected and spiked with internal standard (13 C 6 -T4). The IRMM-468 certified primary reference material (JRC, Belgium) of T4 was used for assay calibration. FT4 in dialysate was extracted with ISOLUTE-96-well C18 SPE plates (Biotage) before LC-MS/MS analysis. T4 could be resolved from Triiodothyronine (T3), reverse triiodothyronine (rT3), and other interferences in the dialysate on a C18 UPLC column with an elution time of less than 8 min. Selective reaction monitoring in positive electrospray ionization mode was used for detection. The measuring range covered 1-100 pg/mL of FT4. The assay sensitivity allowed detection of 0.5 pg/mL FT4, which is sufficient for detection of FT4 in normal and hypothyroid patient samples. The difference of this method to the CDC FT4 RMP was within ±5%. The imprecision of the routine assay, evaluated over four different days, was less than 10% CV. The slopes of calibration curves in dialysate matrix and water were comparable with each other indicating no significant matrix effect on FT4 quantification. The use of micro-ED plates in combination with an automated liquid handling system allows for effective automation of the procedure. The stability of T4 calibrator stock and working solutions were confirmed at various conditions. Currently, a comprehensive comparison study is underway between the newly developed routine method and the CDC FT4 RMP. The described routine FT4 assay can significantly improve throughput. The sensitivity, precision, and accuracy are suitable for routine FT4 measurements in clinical laboratories and conducting large epidemiologic studies. Applying this FT4 routine method to generate population data will support the use of standardized FT4 measurements and to address data needs on FT4 in general population. Presentation: No date and time listed

Development of solid support using protein A for the measurement of free thyroxine in human serum

Development of solid support using protein A for the measurement of free thyroxine in human serum

Association between phenols and thyroid hormones: The role of iodothyronine deiodinase genes

Previous literature on prenatal phenol exposure and thyroid hormone (TH) alteration is conflicting, and the possible mechanisms of action involved remain unclear. We aimed to examine the association between prenatal phenol exposure and levels of maternal and neonatal THs, as well as the possible role of iodothyronine deiodinase (DIO) gene polymorphisms in this relation.We studied 387 Spanish mother–neonate pairs with measurements of maternal phenols, total triiodothyronine (TT3) and free thyroxine (FT4), maternal and neonatal thyroid-stimulating hormone (TSH), and maternal genotypes for single nucleotide polymorphisms in the DIO1(rs2235544) and DIO2(rs12885300) genes. We implemented multivariate linear and weighted quantile sum (WQS) regressions to examine the association between phenols and THs (including sex-stratified models for neonatal TSH) and investigated effect modification of genotypes in the maternal phenol-TH associations.In single exposure models, we found negative associations between maternal triclosan (TCS) and neonatal TSH (% change [95%CI]: −2.95 [-5.70, -0.11], per twofold phenol increase) – stronger for girls – and less clearly for maternal ethylparaben (EPB) and TSH (−2.27 [-4.55, 0.07]). In phenol mixture models, we found no association with THs. In the genetic interaction models, we found some evidence of effect modification of DIO gene polymorphisms with stronger negative associations between methylparaben (MPB), propylparaben (PPB), butylparaben (BPB) and TT3 as well as bisphenol A (BPA) and FT4 for DIO1(rs2235544)-CC. Stronger inverse associations for genotypes DIO2(rs12885300)-CC and DIO2(rs12885300)-CT and positive ones for DIO2(rs12885300)-TT were also reported for BPA and FT4.In conclusion, we found some evidence of an association between phenols and TSH during pregnancy and at birth in single exposure models, the latter being stronger for girls. Since no association was observed between maternal levels of phenols and TT3 or FT4, the possible role of the genetic background in these associations warrants further investigation.

The effects of thyroidectomy on healing fracture in rabbits model

This research aims to investigate the fracture healing effects caused by thyroidectomy. The experiment involved sixteen matured male rabbits of local breed which divided into 2 equal groups (control and treated). Rabbits anesthetized by premedicated atropine sulphate, then 15 minutes later, a mixture of Xylazine Ketamine was used. The control group rabbits were induced with mid-shafted femoral fracture, with that, the fixation by intramedullary pinning was considered Meanwhile, the treated group rabbits were induced with same method mentioned above, but fracture were fixed after thyroidectomy and measurement of thyroxin a week after thyroidectomy. Results which were obtained from the clinic revealed signs of severe inflammatory reaction in control group which were higher comparing to treated group. These sings were disappeared within 4-5 days in treated group, while, it took 5-6 days in control animals. Also, radiological results of 2 groups showed that a periosteal reaction was observed towards the end of the 2nd week in the control group, whereas, the treated group showed its reaction at the end of fourth week, there was an invisible fracture line for both control and treated groups at the end of fourth and seventh week, respectively. In addition, bony bridge in the control groups became remodeled into a lamellar bone earlier than treated group. The results of measuring thyroxin hormone before and after the thyroidectomy confirmed the essential role of this hormone in fracture healing. To conclude that the fracture healing maturity was greater in control group than in treated group.

Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans

Cardiovascular disease is the leading cause of death in the United States. Synthetic thyroid hormones are among the 3 most commonly prescribed medications, yet studies evaluating the association between the intensity of thyroid hormone treatment and cardiovascular mortality are scarce. To evaluate the association between thyroid hormone treatment intensity and cardiovascular mortality. This retrospective cohort study used data on 705 307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004, and December 31, 2017, with a median follow-up of 4 years (IQR, 2-9 years). Two cohorts were studied: 701 929 adults aged 18 years or older who initiated thyroid hormone treatment with at least 2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373 981 patients with at least 2 free thyroxine (FT4) measurements. Data were merged with the National Death Index for mortality ascertainment and cause of death, and analysis was conducted from March 25 to September 2, 2020. Time-varying serum thyrotropin and FT4 levels (euthyroidism: thyrotropin level, 0.5-5.5 mIU/L; FT4 level, 0.7-1.9 ng/dL; exogenous hyperthyroidism: thyrotropin level, <0.5 mIU/L; FT4 level, >1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT4 level, <0.7 ng/dL). Cardiovascular mortality (ie, death from cardiovascular causes, including myocardial infarction, heart failure, or stroke). Survival analyses were performed using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates. Of the 705 307 patients in the study, 625 444 (88.7%) were men, and the median age was 67 years (IQR, 57-78 years; range, 18-110 years). Overall, 75 963 patients (10.8%) died of cardiovascular causes. After adjusting for age, sex, traditional cardiovascular risk factors (eg, hypertension, smoking, and previous cardiovascular disease or arrhythmia), patients with exogenous hyperthyroidism (eg, thyrotropin levels, <0.1 mIU/L: adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32-1.47; FT4 levels, >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (eg, thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55-2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50-1.63) had increased risk of cardiovascular mortality compared with individuals with euthyroidism. This study suggests that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

Biomarkers indicating tissue thyroid hormone status: ready to be implemented yet?

Currently, thyroid hormone status is predominantly determined by the measurement of serum thyroid-stimulating hormone and free thyroxine. Although it is assumed that serum thyroid hormone (TH) concentrations within the reference range represent euthyroidism, it is unknown whether this reflects euthyroidism in all tissues (e.g. brain, muscle, bone and liver). To date, no serum marker has been established for clinical use that represents TH status within tissues accurately. However, several biomarkers have been investigated and innovative techniques have been used to unravel new biomarkers. This review provides an overview of proposed serum biomarkers that reflect tissue TH status in humans. Furthermore, we discuss the feasibility of these serum markers in clinical practice.

M254 Improving the accuracy and reliability of free thyroxine (FT4) measurements through the CDC clinical standardization programs (CSP) using the IFCC reference system for FT4

M254 Improving the accuracy and reliability of free thyroxine (FT4) measurements through the CDC clinical standardization programs (CSP) using the IFCC reference system for FT4

Effects of calorie intake and sampling time on thyroid stimulating hormone concentration

BackgroundThis study aimed to investigate the effects of blood sampling after calorie intake on thyroid stimulating hormone (TSH) level, compared with blood sampling in fasting state.MethodsThis was a prospective, randomized, controlled study. Subjects from the outpatients in the department of endocrinology without evidence of thyroid diseases were included and then randomized into the fasting group, diet intake group, and glucose intake group, respectively. Fasting blood was collected from all subjects at 7:00 am for the measurement of TSH and free thyroxine (FT4) concentrations. Afterwards, the subjects were maintained at fasting state (fasting group), had an intake of the mixed diet with 400 kcal calories (diet intake group), and had an intake of 75 g glucose (glucose intake group), respectively, and blood was collected again 2 h later (9:00 am on the same day) for TSH and FT4 level measurement and comparison.ResultsA total of 150 subjects were enrolled, of whom 146 met the inclusion criteria, with 48, 48, and 50 in the diet intake group, glucose intake group, and fasting group, respectively. The TSH in the diet intake group was significantly lower at 9:00 am (TSH9am) than the level at 7:00 am (TSH7am) (P < 0.001), with a median variation of -0.71 mU/L, and a median variation rate of -32.4%. In the glucose intake group, TSH9am was also significantly lower than TSH7am (P < 0.001), with a median variation of -0.73 mU/L, and a median variation rate of -31.5%. For the fasting group, TSH9am decreased slightly but was significantly lower than TSH7am (P < 0.001), with a median variation of -0.1 mU/L, and a median variation rate of -5.2%. According to TSH7am measurements, 9 subjects (3 subjects in each group) met the diagnostic criteria of subclinical hypothyroidism. However, according toTSH9am measurements, only 2 patients in the fasting group met the diagnostic criteria of subclinical hypothyroidism.ConclusionCompared with the fasting state, the TSH level at 2 h after the calorie intake was decreased by about 30%, which might influence the diagnosis of subclinical hypothyroidism.Trial registrationChiCTR2100047454 (18/06/2021).

Free thyroxine measurement by analogue immunoassay and equilibrium dialysis in dogs with non-thyroidal illness

ObjectivesMeasurement of free T4 by analogue immunoassay (fT4a) is popular but its ability to differentiate hypothyroidism from non-thyroidal illness (NTI) is unclear. The aims were to assess fT4a concentrations in dogs with NTI and to explore diagnostic agreement with total T4 and free T4 measured by equilibrium dialysis (fT4d). MethodsfT4a was measured in dogs classified with mild, moderate and severe NTI. Total T4 and fT4d were measured in a subgroup of these dogs. Results146 dogs were included of which 84, 35 and 27 had mild, moderate and severe NTI, respectively. Median (range) fT4a concentrations (pmol/L) were significantly lower (P = 0.023 and P < 0.001) in dogs with severe (3.86 (3.86–23.60)) compared with moderate (11.10 (3.86–34.70)) and mild (15.25 (3.86–48.60)) NTI. Overall, 49 (33.6% [95% CI, 26.4–41.6]) dogs had low fT4a concentration. All thyroid hormones were measured in 74 dogs. Agreement was substantial between total T4 and fT4a (κ=0.79 [95% CI, 0.65–0.92]) and fT4a and fT4d (κ =0.63 [95% CI, 0.47-0.79]) but moderate between total T4 and fT4d (κ=0.49 [95% CI, 0.32–0.66]). Of 42 dogs with low total T4 concentration, five (11.9% [95% CI, 5.19–24.99]) and 18 (42.9% [95% CI, 29.12–57.80]) had fT4a and fT4d within reference interval, respectively. Conclusions and clinical importancefT4a and fT4d cannot be used interchangeably. Measurement of fT4a provides limited further diagnostic information over measurement of total T4 in dogs with NTI. This study raises concerns regarding the ability of fT4a to differentiate NTI from hypothyroidism in dogs with low total T4 concentrations.

Association of serum thyroid hormone levels with positron emission tomography imaging in non-demented older adults.

Although increasing evidence indicates that even variations in normal range thyroid function are associated with Alzheimer's disease (AD), the association between serum thyroid hormone levels within the reference range and AD biomarkers remains unclear. This study examined whether variations in thyroid hormones within the reference range are associated with brain amyloid burden and cortical glucose metabolism in older adults without dementia. One hundred and two non-demented older adults underwent 11 C-Pittsburgh Compound B positron emission tomography (PiB-PET), 18 F-fluorodeoxyglucose (FDG)-PET, and measurement of serum thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels. The discrimination between PiB-negative and PiB-positive subgroup was made on the basis of a subject's cortical uptake value ratio greater than 1.4. The association of serum thyroid hormone levels with global PiB or FDG uptake, and PiB or FDG uptake in each region of interest, including frontal and temporoparietal lobes and posterior cingulate gyrus, was analysed using a multiple regression model with adjustment for covariates, including age, gender, years of education, apolipoprotein E4 status or PiB uptake value. In the PiB-positive subgroup, the serum TSH levels positively associated with the global FDG uptake (β=0.471, P=0.003) and FDG uptake in the frontal and temporoparietal lobes (β=0.466, P=0.003, β=0.394, P=0.012, respectively); the serum-free T3 levels negatively associated with the FDG uptake in the temporoparietal lobe and posterior cingulate region (β=-0.351, P=0.033, β=-0.544, P=0.002, respectively). The PiB-negative subgroup showed no significant associations. The serum thyroid hormone levels did not correlate with the global PiB uptake and PiB uptake in each region. The variations in the thyroid hormones within the reference ranges are associated with glucose metabolism, particularly in the specific regions affected by the neuropathologic changes of AD, in non-demented older adults with brain amyloid burden.

Worse Outcomes in Patients With Depression Linked to Low Thyroid Hormones

Worse Outcomes in Patients With Depression Linked to Low Thyroid Hormones

A Comparative Study of the Levels of Heat Shock Protein 70, Some Biochemical and Hormonal in the Blood of Cows Suffering from Follicular Cystic Ovarian and Endometritis

Twenty- four reproductive systems of Frisian cross breed cows, aged between (3-5years) were obtained from Basrah abattoir during the period of (2nd March 2020 - 30th June, 2020). They were divided into 3 groups of cows with ovarian follicular cystic (n=8), cows with endometritis (n = 8), and healthy cows (n=8) depending on clinical signs. The main gall of this paper compare and report the different values of heat shock protein 70 (HSP70), some biochemical and hormonal levels in those cows in the native Basrah climate. Samples of blood were collected from all cows subjected to this study and serum was harvested from each individual sample by centrifugation. Heat shock protein 70 (Hsp70), total protein (TP), albumin(Alb), globulin, total cholesterol (Cho), triglyceride (TG), low density lipo-protein(LDL), aspartate aminotransferase (AST), cortisol, testosterone, thyroid stimulation hormone (TSH), thyroxin (T4) and triiodothyronine hormones(T3) were measured in serum samples. Results revealed a significant increase (p≤0.05) in the level of Hsp70, and thyroid stimulation hormones (TSH) of cows with two pathological cases (endometritis and follicular cysts) compared with those healthy cow. Significant decrease (p≤0.05) in the measurement of total protein, albumin, globulin, thyroxin (T4), triiodothyronine (T3) hormones, cholesterol, triglyceride, and low density lipoprotein (LDL) in cows having those two genital diseases compared with normal cows. The results also were revealed a significant increase (p≤0.05) in the level of testosterone hormone in cows with follicular cystic ovarian case compared with endometritis case and control ones. Finally, significant increase (p≤0.05) in cortisol hormone level and aspartate aminotransferase (AST) activity in cows with endometritis case compared with the control one and follicular cystic ovarian cases.