Effect of Radioimmunoassay on Accuracy of Thyroid Hormone Detection.

At present, the most important method for the detection of thyroid hormones in hospitals in China is radioimmunoassay. Besides radioimmunoassay, there are blood test and antibody test methods for thyroid hormone detection. However, after long-term clinical investigations, the accuracy of the results of thyroid hormone detection by radioimmunoassay has been affected by many factors. Possible influencing factors include inaccurate thyroid hormone test results due to improper way of blood collection by nurses and improper way of keeping and transporting blood samples by nurses. Therefore, this paper analyzes and discusses the influencing factors of the accuracy of thyroid hormone (T4) detection by radioimmunoassay technology. In this paper, we conducted research using statistical analysis of clinical data, improved separation methods for quality control in the laboratory, and blood specimen collection methods. Radioimmunoassay occurs with antibodies. Of the 10 batches of 964 cases in the improved separation methods for quality control in the laboratory, 154 mismatched items accounted for 16%, and the error of method and operation only accounted for 5.8% of unmatched specimens, most of which were the biochemical characteristics and clinical manifestations of thyroid hormones. The blood sample collection method research found that mild hemolysis had no significant effect on the measurement results, severe hemolysis had a tendency to affect the results, and blood collection tubes had no effect on the test results. Mild hemolysis refers to the increase in the rate of red blood cell destruction due to various internal and external factors in the body. The symptoms when mild hemolysis occurs are generally not obvious. Severe hemolysis refers to a disease caused by blood group incompatibility, mainly referring to immune hemolysis caused by blood group incompatibility between mother and baby, as well as severe jaundice or severe anemia. The statistical analysis of clinical data found that, among 160 patients, the reasons for the inaccuracy of T4 results using radioimmunoassay technology were as follows: 104 patients were inaccurate due to personal factors, and the results were due to hospital factors. A total of 56 patients had inaccurate results. During the measurement of thyroid hormone, it will be affected by many factors. For this reason, the influencing factors of the accuracy of radioimmunoassay should be clarified, and appropriate measures should be taken to deal with it, so as to give full play to the role of radioimmunoassay and improve the detection.

Development of a selective fluorescence derivatization strategy for thyroid hormones based on the Sonogashira coupling reaction.

A new fluorescence derivatization technique for the determination of the thyroid hormones, 3,3',5-triiodo-L-thyronine (T3, triiodothyronine) and 3,3',5,5'-tetraiodo-L-thyronine (T4, L-thyroxine), in human serum was developed based on the Sonogashira coupling reaction. This derivatization reaction was recently utilized by our research group as a promising solution for the derivatization of ortho-substituted aryl halides that suffer from steric hindrance. T3 and T4 possess amino groups that could be derivatized by many reagents; however, these reagents are not useful in the case of biological analysis as they could non-selectively react with many biogenic amines and amino acids. Thus, herein we aimed at labeling the iodo-phenyl group of T3 and T4 as a selective fluorescence labeling approach suitable for biological analysis. The fluorescent alkyne, 2-(4-ethynylphenyl)-4,5-diphenyl-1H-imidazole (DIB-ET), can label the ortho-substituted aryl halides T3 and T4 in the presence of palladium and copper as catalysts, overcoming the steric hindrance of ortho-substitution. Furthermore, the application of the proposed method for the selective analysis of T3 and T4 in biological samples was successfully performed even in the presence of numerous biological components. The formed fluorescent derivatives produced from the reaction of DIB-ET and T3 and T4 could be determined by an HPLC system with fluorescence detection. The proposed method was successfully applied for the selective and sensitive determination of T3 and T4 in human serum with detection limits (S/N = 3) of 4.0 and 6.1 ng/mL and the recovery rate in the ranges of 84.3-92.1% and 81.3-84.9%, respectively. Therefore, the proposed method could be used as a new simple tool for the simultaneous determination of T3 and T4 in biological samples.

Associations between the thyroid panel and serum protein concentrations across pregnancy.

Establishing any characteristic associations between the serum parameters of thyroid function and serum proteins in pregnancy may aid in elucidating the role of the thyroid gland in the regulation of pregnancy-specific metabolic processes and in selecting candidate biomarkers for use in their clinical assessment. Concentrations of thyroid stimulating hormone (TSH), free tri-iodothyronine (fT3) and free thyroxine (fT4), six electrophoretically separated protein fractions (albumin, alpha-1-, alpha2-, beta-1-, beta-2- and gamma-globulins), representative proteins-albumin (ALB), transferrin (TRF), alpha-2-macroglobulin (AMG) and ceruloplasmin (CER) were measured in 136 serum samples from 65 women in their consecutive trimesters of pregnancy. The concentrations of TSH, fT4 and fT3 were significantly correlated (p < 0.05) with the concentrations of the albumin, alpha-2- and beta-1 globulin fractions. Significant correlations (p < 0.05) which were positive between fT4 and ALB and negative between fT4 and TRF were established throughout pregnancy. Significant negative correlations (p < 0.05) were demonstrated for fT3 with alpha-2-globulin, AMG and CER. Changes in the serum concentrations of thyroid hormones seen between the trimesters were found to correlate with the concentrations of high-abundance serum proteins. Opposite directions of correlations between fT4 and ALB and fT4 and TRF observed throughout pregnancy may indicate the shared biological role of these parameters in maintaining maternal homeostasis and they suggest their potential use in the clinic as a simple biomarker panel. A negative correlation of fT3 with CER in the second trimester possibly reflects their involvement in the active regulation of metabolic processes.

Prognostic role of hypothyroidism and low free-triiodothyronine levels in patients hospitalized with acute heart failure.

Low thyroid function has been widely recognized as a potential cause of heart failure (HF), but the evidence about a possible association with in-hospital, all-cause mortality in patients with acute HF (AHF) is not consistent. This study sought to investigate the prevalence and prognostic role of hypothyroidism, overt and subclinical, and of low free-triiodothyronine (fT3) levels in patients hospitalized with AHF. We retrospectively analyzed consecutive 1018 patients who were hospitalized for AHF in a single academic medical center [Fondazione Policlinico A.Gemelli IRCCS, Rome, Italy] between January 1st 2016, and December 31st 2018. Patients were divided into three groups: normal thyroid function (n = 798), subclinical hypothyroidism (n = 105), and overt hypothyroidism (n = 115). The outcome was in-hospital, all-cause mortality. Patients were 81 years of age, 55% were females and nearly two-thirds of the patients were on New York Heart Association functional class III. The three most common cardiovascular comorbidities were coronary artery disease, hypertension, and atrial fibrillation with no differences across the three groups. Overall, 138 patients (14%) died during the hospital stay. The mortality rate was 27% among patients with overt hypothyroid, 17% among those with subclinical hypothyroidism, and 11% among euthyroid patients (p < 0.001). At a multivariate Cox regression model, overt hypothyroidism (HR 2.1, 95% CI 1.4-3.2) and fT3 levels < 1.8 pg/mL (HR 3.4, 95% CI 2.3-5.1) were associated with an increased likelihood of in-hospital death. No association was found with subclinical hypothyroidism. Among patients hospitalized with AHF, overt hypothyroidism and low fT3 levels are independent predictors of all-cause mortality during the hospital stay.

Characterization of intestinal microbiota and fecal cortisol, T3, and IgA in forest musk deer (Moschus berezovskii) from birth to weaning.

Analysis of the intestinal microbiota and physiological parameters in mammalian infancy can reveal health status. In this study, we used a combination of molecular and immunochemical approaches to assess fecal microbiota as well as Cortisol (Cor), Triiodothyronine (T3), and immunoglobulin A (IgA) levels of young forest musk deer (FMD), from birth to one month after weaning (7 days of age-110 days of age). During development as the diet of FMD changes from consuming milk to eating plants, the richness and diversity of intestinal microbiota of young FMD increased significantly. Cor levels remained unchanged throughout early development while significantly increased after weaning, T3 and IgA initially were derived from milk during lactation, significantly decreased after weaning. Correlation network analysis showed that the community of food-oriented microbes were highly structured and that many genera were correlated. Overall, this study provides scientific insights into effective management strategies for the protection of FMD population.

Laboratory interference in the thyroid function test.

Thyroid hormones and thyroid-stimulating hormone (TSH) laboratory tests are commonly used worldwide, and their results have an important influence on decisions about treatment and further diagnostic processes. Any discrepancies between symptoms and laboratory results or between results of different tests should be closely investigated to avoid misdiagnosis and unnecessary treatment. Inconsistencies in hormone tests might be a result of physiological changes in hormonal balance, a disease, drug intake, or laboratory interference. Major factors that interfere with thyroid function tests are: heterophilic antibodies, macro TSH, biotin, thyroid hormones autoantibodies, anti-streptavidin, and anti-ruthenium antibodies. In this paper we discuss the influence of different factors on the procedures of hormonal immunoassays, as well as methods to minimise the risk of false results and misdiagnoses.

Study of reference intervals for free triiodothyronine, free thyroxine, and thyroid-stimulating hormone in an elderly Chinese Han population.

The clinical manifestations of thyroid diseases in elderly patients are often atypical. This study aimed to establish reference intervals for thyroid function in the elderly in order to help diagnose thyroid diseases in this population. A total of 5345 healthy individuals were examined and divided into three groups according to their age: 4297 individuals aged < 65 years (19-64), 719 individuals aged between 65 and 79 years, and 329 individuals aged between 80 and 100 years. Levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody, and thyroglobulin antibody were measured in these subjects by using a fully automated analyzer. The following free triiodothyronine, free thyroxine, and thyroid-stimulating hormone reference intervals were obtained from each age group: For individuals aged < 65 years (19-64 years), FT3, FT4, and TSH were 3.40-6.44, 10.26-19.25 pmol/L and 0.50-4.81 µIU/mL, respectively. For individuals aged between 65 and 79 years, FT3, FT4 and TSH ranged between 3.01-5.91, 10.04-19.76 pmol/L, and 0.54-5.51 µIU/mL, respectively. For individuals aged between 80 and 100 years, FT3, FT4, and TSH varied between 2.82-5.57, 9.79-21.22 pmol/L, 0.31-6.28 µIU/mL respectively. FT3 concentration was lower and the concentrations of FT4 and TSH were higher in individuals aged ≥ 65 years than in those aged <65 years (P<0.0001; P = 0.0039; P<0.0001, respectively). In conclusion, establishment of a reference interval would allow clinicians to diagnose diseases more accurately and easily.

Interpretation of thyroid function tests during pregnancy.

Thyroid hormones are crucial for normal pregnancy and fetal development. Large physiological changes occur during pregnancy, posing challenges for the correct interpretation of thyroid function tests. TSH concentrations are the principal first test to rule out thyroid disease taking into account trimester-specific reference ranges. Free T4 (FT4) measurements by immuno-assays may be subject to interference by endogenous and exogenous factors. The relevance of measuring free T3 (FT3) during pregnancy is unclear. Thyroid autoimmunity is well-reflected by the presence of antibodies against TPO. TPO-antibody positivity is associated with an increased risk of adverse pregnancy outcomes.

Altered thyroid hormone profile in patients with Alzheimer's disease.

BACKGROUND: Epidemiological studies have linked higher levels of thyroid hormones (THs) to increased risk of Alzheimer's disease (AD), whereas in advanced AD, THs have been unchanged or even decreased. In early AD dementia, little is known whether THs are related to AD neuropathology or brain morphology. METHODS: This was a cross-sectional study of 36 euthyroid AD patients and 34 healthy controls recruited at a single memory clinic. Levels of THs were measured in serum and cerebrospinal fluid (CSF). In addition, we determined AD biomarkers (amyloid-ß1-42, total tau and phosphorylated tau) in CSF and hippocampal and amygdalar volumes using magnetic resonance imaging. RESULTS: Serum free thyroxine (FT4) levels were elevated, whereas serum free triiodothyronine (FT3)/FT4 and total T3 (TT3)/total T4 (TT4) ratios were decreased, in AD patients compared to controls. In addition, serum TT4 was marginally higher in AD (p = 0.05 vs. the controls). Other TH levels in serum as well as CSF concentrations of THs were similar in both groups, and there were no correlations between THs and CSF AD biomarkers. However, serum FT3 correlated positively with left amygdalar volume in AD patients and serum TT3 correlated positively with left and right hippocampal volume in controls. CONCLUSIONS: Thyroid hormones were moderately altered in mild AD dementia with increased serum FT4, and in addition, the reduced T3/T4 ratios may suggest decreased peripheral conversion of T4 to T3. Furthermore, serum T3 levels were related to brain structures involved in AD development.

Association between Abdominal Fat Distribution and Free Triiodothyronine in a Euthyroid Population.

BACKGROUND: Obesity is closely related to thyroid hormones; however, the relationship between abdominal fat distribution and thyroid hormones has rarely been explored. OBJECTIVES: This study aimed to explore the relationship between abdominal fat distribution and free triiodothyronine (FT3) and FT3 to free thyroxine (FT4) ratio (FT3/FT4) in a euthyroid population. METHODS: The present study enrolled 1,036 participants (age range 27-81 years; 445 men and 591 women). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were determined by magnetic resonance imaging. FT3, FT4, and thyroid-stimulating hormone were measured by an electrochemical luminescence immunoassay. RESULTS: In both men and women, SFA increased according to the increase of FT3 and FT3/FT4 tertiles (p for trend <0.05), while VFA did not significantly change. In the multivariate stepwise regression analysis, SFA was independently and positively related to FT3 in both men and women, the standardized ß (95% CI) were 0.183 (0.094, 0.272) (p < 0.001) and 0.089 (0.007, 0.171) (p = 0.033), respectively. Moreover, SFA was independently and positively related to FT3/FT4 in men, the standardized ß (95% CI) was 0.196 (0.101, 0.290) (p < 0.001). However, VFA was not related to either FT3 or FT3/FT4 in both genders. CONCLUSIONS: Abdominal subcutaneous fat was independently related to increased FT3 in a euthyroid population.

Flexible MoS2-Polyimide Electrode for Electrochemical Biosensors and Their Applications for the Highly Sensitive Quantification of Endocrine Hormones: PTH, T3, and T4.

Flexibile biosensors have a lot of applications in measuring the concentration of target bioanalytes. In combination with its flexibility, electrochemical sensors containing 2D materials have particular advantages such as enlarged area compatibility, transparency, and high scalability. A flexible biosensor was fabricated by direct synthesis of molybdenum disulfide (MoS2) on a polyimide (PI) substrate, which can be used as the working electrode in electrochemistry platforms. The direct formation of 2D-MoS2 on the PI was achieved using plasma-enhanced chemical vapor deposition (PE-CVD). Since the MoS2 provides higher electrical conductivity, the MoS2-Au-PI flexible sensor is able to provide highly sensitive detection of target proteins with a relatively fast response via cyclic voltammetry. To evaluate the high performance of the fabricated sensor, we selected the endocrine-related hormones parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) as analytes because they are one of the most important markers for the determination of endocrinopathy, however, they are very difficult to quantify. The newly developed biosensor achieved highly sensitive detection of the hormones and could determine their location with high accuracy. In addition, we performed electrochemical measurements of hormones obtained from 30 clinical patients' sera with confirmed agreement and compared with the measurements performed with standard immunoassay equipment (E 170, Roche Diagnostics, Germany).

Ultra performance liquid chromatography - tandem mass spectrometer method applied to the analysis of both thyroid and steroid hormones in human hair.

Hair is increasingly used as a biological matrix of interest for the assessment of hormone secretion over extended periods of time. This study described the development and the validation of a sensitive UPLC-MS/MS method for simultaneous analysis of steroid and thyroid hormones in human hair. The gradient designed in this method enables to obtain a satisfactory separation of 9 hormones of interest: cortisol, cortisone, THE, THF, α-THF, triiodothyronine (T3) and thyroxine (T4), estradiol, and testosterone. Several methodological parameters of extraction (such as the used of "cut hair" versus "pulverized hair", the extraction time, the incubation solvent purification on SPE column and hydrolysis) that may influence the determination of hormones levels in human hair, have thus been tested here. Therefore, the results obtained highlighted the necessity of using a C18 SPE purification method for the determination of both steroid and thyroid hormones in hair. This method allows reaching suitable levels of sensitivity for cortisol and cortisone since the results obtained pointed out concentration levels of cortisol in hair of volunteers similar to those observed in the literature. This method could also offer an important impact in the field of hormone analysis since it allows, for the first time, the quantification of both T3 and T4 in human hair.

Abnormal thyroid hormone receptor signaling in osteoarthritic osteoblasts regulates microangiogenesis in subchondral bone.

AIMS: Previous study indicated that the increase of local bio-availability of 3'3'5-triiodothyronine (T3) influenced osteoarthritis (OA) initiation. We aimed to investigate the role of thyroid hormone receptors (THRs) signaling in OA osteoblasts. MATERIALS AND METHODS: THRs expression in OA was detected by immunohistochemistry, immunofluorescence, RT-qPCR and western blotting. These effects on the expression of angiogenesis-related factors were examined after THRα or THRß knockdown in OA osteoblasts. Fluorescence in situ hybridization was used to confirm the leading receptor for regulating angiogenesis-related factors. Co-culture model was utilized to observe the MMPs expression in chondrocytes after THRα knockdown in osteoblasts. The in vivo effects were also studied after intra-articular injection with THRα siRNA in OA model mice. Micro-CT and immunohistochemistry were employed to evaluate the changes of subchondral bone. KEY FINDINGS: THRs expression and nuclear translocation were upregulated in human OA osteoblasts. Immunohistochemistry showed that angiogenic activities were increased in OA subchondral bone of human and mice. VEGF, HIF-1α and IGF-1, these THR downstream genes were downregulated after THRα knockdown in OA osteoblasts. Fluorescence in situ hybridization further indicated that THRα signaling mainly regulated VEGF expression. Intra-articular injection with THRα siRNA reduced angiogenic activities in OA model mice subchondral bone and ameliorated cartilage degradation. Micro-CT analysis displayed that the aberrant subchondral bone formation in OA was promoted. SIGNIFICANCE: The microangiogenesis in subchondral bone may be partly attributed to abnormal THRα signaling in osteoblasts, and local inhibition of the THRα could be a potential target to treat OA.

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh's indirect method after exclusion of individuals younger than 15 years, subjects with repeated TSH tests and with abnormal free thyroxine (fT4), free triiodothyronine (fT3) or anti-thyroid-peroxidase antibodies. The combined effect of age and gender on TSH values was evaluated. Results RIs estimated in the selected individuals (n = 22602) were, respectively, 0.18-3.54 mIU/L (general), 0.19-3.23 mIU/L (men) and 0.18-3.94 mIU/L (women). Women showed significantly higher median TSH than men (1.46 vs. 1.39 mIU/L; p < 0.0001). Both in men and in women, median TSH decreased along with age; however, although up to 60 years in both men and women showed similar values, afterwards women showed constantly higher TSH than men. Accordingly, statistical analysis showed a significant interaction between gender and age (p = 0.001), suggesting that the effect of age on TSH is different between genders. Conclusions Our findings suggest that the indirect method, with appropriate cleaning of data, could be useful to define TSH RIs.

Negative association between free triiodothyronine level and contrast-induced acute kidney injury in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: A low FT3 level is significantly associated with a variety of kidney disease and acute myocardial infarction (AMI). However, it remains unclear whether low FT3 is associated with CI-AKI in patients who underwent pPCI. METHODS: Single-center retrospective study evaluated 363 STEMI patients undergoing pPCI. Patients were classfied into 2 groups, low FT3 group (FT3 < 3.1 pmol/L) and normal FT3 group (FT3 ≥ 3.1 pmol/L);CI-AKI was defined as an increase in the serum creatinine levels of ≥50% or 0.3 mg/dL above the baseline level within 48 h after contrast medium exposure. RESULTS: Overall, 80(22.0%) patients had low FT3, and 59(16.3%) patients developed CI-AKI. The incidence of CI-AKI and in-hospital mortality was significantly higher in patients with low FT3 than normal (31.3% vs 12.0%; 15.0% vs 3.2%, respectively, both p < 0.0001). Multivariate logistic regression analysis indicated that low FT3 was an independent predictor of CI-AKI (odds ratio [OR] = 2.62, 95%CI:1.35-5.07, p < 0.05). In addition, low FT3 was associated with an increased risk of all-cause mortality during a mean follow-up period of 20 months (hazard ratio [HR] = 2.54, 95%CI:1.15-5.60, p < 0.05). CONCLUSION: Low FT3 was associated with CI-AKI, short- and long-term mortality in STEMI patients after pPCI.

Neuroendocrine abnormalities associated with untreated first episode patients with major depressive disorder and bipolar disorder.

There are few studies that explore simultaneously the relationship of neuroendocrine hormones of the HPA, HPT and HPG axes with major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study is to examine the relationship of neuroendocrine pathways with affective disorders by comparing the differences in measures of neuroendocrine function between untreated first episode patients with MDD and BD. A cohort of 679 MDD and 83 BD patients was recruited. Thyroid stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), free thyroxin (FT4), cortisol (COR), adrenocorticotropic hormone (ACTH), estradiol (E2) and testosterone (T) were determined by chemiluminesent immunoassay for all patients. COR and ACTH were both significantly higher in the MDD group than those in BD group. The incidences of high secretion of ACTH and COR, and low thyroid hormone secretion were significantly greater in MDD patients than in BD patients. Decreased T secretion was more common in BD than MDD patients. ACTH was significantly positively correlated with HAMD total score and negatively correlated with FT3 in MDD patients. FT3 and FT4 levels were significantly negatively correlated with the somatoform factor score of HAMD in MDD patients. Untreated first episode patients with MDD have a hyperactivity of the HPA axis, lower HPT compared with BD patients. BD patients had reduced testosterone secretion. These findings indicate that ACTH, FT3 and FT4 could be used as markers for severity and symptoms of untreated first episode patients with MDD.

Determination of thyroid hormones in human hair with online SPE LC-MS/MS: Analytical protocol and application in study of burnout.

Thyroid hormones (THs) play a key role within the endocrine system. Incorporated biomarkers in hair can reflect endogenous excretion patterns over several months. We present an online solid phase extraction-liquid chromatography-mass spectrometry (online SPE-LC-MS/MS) method for quantification of THs in human hair and test it in the volunteers suffering from different severity of burnout symptom. THs were extracted from 7.5 mg hair by methanol incubation. Extracts were analyzed with LC-MS/MS in positive electrospray ionization mode. Burnout symptoms were assessed with the Maslach Burnout Inventory-General Survey (MBI-GS). THs levels were determined in 208 hair samples from adults and related to individual MBI-GS score. Intra- and inter-day coefficients of variance were between 3.1% and 10.2%. The recoveries of this method were between 88.5% and 102.1%. Hair T4 levels correlated significantly with total and free T4 in plasma. Participants with high degree of burnout had significantly higher hair T4 levels and lower T3/T4 ratio compared to those with no or moderate degree of burnout. A trend towards higher hair T3 levels was observed in subjects with high burnout score. Hair T4 levels showed a significant positive relationship with MBI-GS score, whereas no significant correlation emerged for hair T3 levels. The negative correlation between T3/T4 ratio and MBI-GS score was also significant. We have developed an online SPE-LC-MS/MS method for measurement of THs in human hair, allowing high analytical specificity and sensitivity. The novel finding of hair THs levels from individuals suffering from chronic stress in burnout underscores the relevance of this method for medical and psychological research.

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p = .051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p = .025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (protein product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in age-related TDP-43 proteinopathy.

Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer's disease.

BACKGROUND: In epidemiological studies, thyroid hormones (THs) have been associated with the risk of dementia. However, little is known of the relation between THs and risk of Alzheimer's disease (AD) or vascular dementia (VaD) in a memory clinic population. METHODS: In a mono-center study, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed in 302 patients. All patients had subjective or objective mild cognitive impairment and none received treatment with THs. Cox proportional hazards regression analyses was used to determine whether THs at baseline were associated with the risk of conversion to all-cause dementia, AD or VaD. RESULTS: During the follow-up (mean 2.8 years), 82 (28%) of the patients progressed to dementia [AD, n = 55 (18%) and VaD, n = 17 (6%)]. Serum concentrations of TSH, FT4, and FT3 did not associate with all-cause dementia or VaD. Higher serum FT3 was associated with lower risk of conversion to AD [hazard ratio (HR) = 054; 95% confidence interval (CI): 0.32-0.92 per 1 pmol/L increase]. Furthermore, patients in the lowest serum FT3 quartile had a twofold increased risk of AD compared to those in the highest quartile (HR = 2.63; 95% CI: 1.06-6.47). These associations remained after adjustment for multiple covariates. CONCLUSIONS: In a memory clinic population, there was an inverse, linear association between serum FT3 and risk of AD whereas THs did not associate with all-cause dementia or VaD. Further studies are needed to determine the underlying mechanisms as well as the clinical significance of these findings.

Effects of breeding center, age and parasite burden on fecal triiodothyronine levels in forest musk deer.

The objective of this study was to evaluate the effects of sex, breeding center and age on fecal triiodothyronine levels in captive forest musk deer Moschus berezovskii, and to explore the age-intensity model of gastrointestinal parasites. Furthermore, the association between fecal triiodothyronine levels and parasite egg shedding was also analyzed. We collected musk deer fecal samples from two breeding centers located in Shaanxi and Sichuan province, China. Enzyme-linked immunosorbent assays were utilized to estimate the fecal triiodothyronine concentrations and profiles, and fecal parasite eggs or oocysts were counted using the McMaster technique. Female deer from both breeding centers consistently showed higher triiodothyronine concentrations than those observed in males, which indicates that a distinct physiology pattern occurs by sex. The triiodothyronine concentration in Sichuan breeding center was significantly higher than that in Shaanxi center for both sexes, suggesting that differences in environment, diet and management practices are likely to affect the metabolism. In addition, a negative relationship between triiodothyronine concentrations and age was found (r = - 0.75, p < 0.001), and parasite egg shedding was also negatively associated with age (r = - 0.51, p < 0.001), by which we can infer that older animals evolves a more developed immune system. Finally, a positive association between parasite egg shedding and triiodothyronine levels was found, which could be explained by the additional energy metabolism resulting from parasitic infection. Results from this study might suggest metabolic and immunological adaptations in forest musk deer. These baseline data could be used to unveil metabolic status and establish parasite control strategies, which has great potential in captive population management as well as their general health evaluations.