TT4 Concentrations Research Articles

Evaluation of a point-of-care test for quantitative determination of total thyroxine in feline serum.

Total thyroxine (TT4) evaluation is the most commonly used first-line test for the diagnosis and monitoring of cats with hyperthyroidism. Vcheck T4 is a point-of-care immunoassay that measures TT4 using a Vcheck V200 analyser. This study aimed to evaluate the analytic performance of the Vcheck T4 assay in feline sera and the agreement in the classification of normal, high and low TT4 concentrations of Vcheck T4 with those measured by an enzyme immunoassay (EIA). Assay precision, reproducibility and linearity were evaluated for the Vcheck T4. For method comparison, TT4 concentrations in 73 serum samples were analysed by both methods. Vcheck T4 demonstrated good precision, reproducibility (intra- and inter-assay coefficients of variation between 3% and 13.5%) and linearity in the diagnostic range of <0.5 and >8 μg/dl. The correlation coefficient was 0.87, Passing-Bablok regression showed a proportional, but not constant bias, Bland-Altman plots revealed a mean difference of +0.5 μg/dl. The overall inter-rater agreement (K) between TT4 EIA and Vcheck results was substantial (K = 0.69), with 82.2% of concordant results. As a diagnostic test for hyperthyroidism, Vcheck T4 showed a sensitivity and specificity of 88.9% and 84.4%, and a positive predictive value (PPV) and negative predictive value (NPV) of 44.5% and 98.2%, respectively. Vcheck T4 assay provided precise and reproducible results in substantial agreement with the EIA. Given the high NPV, Vcheck T4 is useful in ruling out hyperthyroidism when screening cats, but, based on low PPV, samples with results with high TT4 need to be analysed by another reference method. Further analysis with haemolytic, icteric and lipaemic samples is needed to assess the test performance. Finally, the reference intervals provided by the manufacturer require verification, and TT4 intervals specific to this method must be established in future studies.

Prevalence of feline hyperthyroidism in a laboratory-based sample of 27,888 cats in Spain.

The objective of the study was to investigate the prevalence of hyperthyroidism in Spain, including its geographical distribution and prevalence across different age groups. A cross-sectional study was conducted. Samples submitted to a reference laboratory to evaluate serum total thyroxine concentration (TT4) during a 3-year period were evaluated (n = 27,888). A cat was considered hyperthyroid if the TT4 concentration was greater than 60.4 nmol/l (4.7 μg/dl). Hyperthyroid cats were classified based on their TT4 concentration at diagnosis as mildly (TT4 60.4-124.8 nmol/l [4.7-9.7 μg/dl]), moderately (TT4 124.8-249.68 nmol/l [9.7-19.4 μg/dl]) or severely (TT4 >249.6 nmol/l [>19.4 μg/dl]) hyperthyroid. The samples were also grouped by life stage, into young adults (1-6 years old), mature adults (7-10 years old) and seniors (>10 years old). The study included samples from 17 regions of Spain and geographical mapping was based on seven domains. One thousand seven hundred and twenty-two out of 27,888 cats (6.2%, 95% confidence interval [CI] = 5.9-6.5) were classified as hyperthyroid. Within the hyperthyroid group, ages ranged from 2 to 25 years old, with a median of 14 years. Within the hyperthyroid population, 14/368 (3.8%), 27/368 (7.3%) and 327/368 (88.8%) were young adults, mature adults and seniors, respectively. The prevalence of hyperthyroidism in this laboratory-based sample in Spain was 2.7 (95% CI = 0.4-5.7) to 6.9% (95% CI = 6.4-7.4), depending on the geographical region. During the study period, 8.2% of cases that were initially non-hyperthyroid were later diagnosed with hyperthyroidism. Prevalence of hyperthyroidism in Spain is 6.2% (95% CI = 5.9-6.5) overall and 7.9% (95% CI = 7.2-8.8) in cats older than 10 years. The distribution of the disease is heterogeneous between different geographical regions. Further large-scale prospective studies are required to determine the risk factors in each region and understand the reasons for this variation.

Triiodothyronine (T3), but not resting metabolic rate correlates positively with per- and polyfluoroalkyl substances (PFAS) in Arctic terns

In Arctic seabirds, positive correlations between per- and polyfluoroalkyl substances (PFAS) and thyroid hormones (THs) and resting metabolic rate (RMR) have been documented. Herein we investigated levels and patterns of PFAS in Arctic terns (Sterna paradisaea) nesting in Kongsfjorden, Svalbard (Norway), and if circulating concentrations of PFAS correlated with their circulating concentrations of TH, and the RMR of the birds. The hypothesis was that there will be positive correlations between PFAS, TH, and RMR, indicating that PFAS-induced increases in plasma THs could be responsible for the increased RMR. The dominating PFAS in the terns were perfluorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA) and perfluorotridecanoate (PFTrDA). The PFAS pattern was similar to what has been found in other seabirds in Kongsfjorden. There were positive correlations between several PFAS and total triiodothyronine (TT3) concentrations in the terns. When sex was accounted for there were significant correlations in female terns, but not in males. There were no correlations between PFAS and RMR or between TT3 and RMR. This indicates that there is no link between a PFAS-induced increase in plasma TT3 concentrations and a resultant increased RMR. The positive associations between blood PFAS concentrations and plasma TT3 concentrations may be a passive association, as both PFAS and T3 bind to thyroid hormone binding proteins (THBP). We recommend that interrelationships between circulating concentrations of PFAS, THs and THBP are investigated further to identify the role of PFAS as TH disrupting chemicals and chemicals that may affect the RMR in birds.

Thyroid function tests in healthy kittens aged between 2 and 16 weeks.

This study aimed to determine thyroid hormone concentrations in a cohort of healthy kittens due to the paucity of information in the literature, and the potential for congenital hypothyroidism (CH) to contribute to fading kitten syndrome (FKS). The serum concentrations of total thyroxine (TT4), free thyroxine (fT4), total triiodothyronine (TT3), free triiodothyronine (fT3) and thyroid-stimulating hormone (TSH) were measured in 19 healthy kittens aged 2-16 weeks. Mean TT4, fT4, TT3 and fT3 concentrations significantly differed across age groups. Mean TT4 and fT4 concentrations peaked at 6 and 5 weeks of age, respectively. The TT4 concentration exceeded the adult cat reference interval (ACRI) in 54% (32/59) of samples at week 6, with the highest TT4 concentration being 7.1 µg/dl (91 nmol/l). Mean TT3 and fT3 concentrations also peaked at 6 weeks of age. Mean TT3 concentration started below the ACRI until 4 weeks of age, after which it remained within the ACRI. The mean fT3 concentration was within the ACRI at all ages. The mean TSH concentration did not differ across age groups and remained within the ACRI in nearly 100% of samples. Peak TT4, fT4, TT3 and fT3 concentrations in healthy kittens at 5 and 6 weeks of age are likely due to changes in the maternal transfer of thyroid hormones after weaning and organ system development. Knowing healthy neonatal and pediatric thyroid hormone concentrations in a cohort of kittens might help a veterinarian interpret thyroid hormone levels when trying to rule out CH in a kitten with FKS.

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.

Objective: To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. Methods: This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon signed ranks tests and generalized estimated equations to assess effects on thyroid and metabolic markers, and receiver operating characteristics curves to predict optimal dose. Results: Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day. Thyrotropin concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Conclusion: Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans.

Retrospective comparison of thyroid hormones in Steller sea lions Eumetopias jubatus under professional care with and without thyroid disease.

An evaluation of morbidity and mortality in Steller sea lions (SSLs) Eumetopias jubatus under professional care identified a high prevalence of thyroid disease in aged animals. While studies have investigated the effects of age, season, nutrition, stressors, and pollutants on thyroid hormones in pinnipeds, data from individuals with known thyroid disease are lacking. Histopathological reports of adult SSLs in North American aquariums from 1979 to 2022 with banked serum (n = 14) were reviewed. Radioimmunoassays, which have been validated in this species, were used to determine triiodothyronine (TT3), total thyroxine (TT4), and free thyroxine (fT4). A solid-phase chemiluminescent immunometric assay for thyroid-stimulating hormone (TSH) quantification was validated by testing inter- and intra-assay repeatability, recovery, and parallelism. Lesions included follicular cysts (n = 5), adenoma with thyroglossal duct or follicular cysts (n = 2), medullary or follicular C-cell carcinoma with follicular cysts and nodular hyperplasia (n = 1), neuroendocrine carcinoma with follicular cysts (n = 1), and sarcomatoid carcinoma metastasis to the thyroid (n = 1). Significantly lower concentrations of TT3, TT4, and fT4 in SSLs with thyroid disease (n = 10) versus those without (n = 4) were attributed to space-occupying lesions, advanced age, and/or season. TSH was not significantly different between groups. Fifty percent of diseased SSL profiles were within reference ranges, and all individuals with lesions were clinically euthyroid. These data expand the current understanding of thyroid disease in SSLs and underscore the need for additional diagnostics (e.g. cervical ultrasound) concurrently with hormone assays to effectively screen for underlying abnormalities.

Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary-Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats.

Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary-thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats.

Total thyroxine, triiodothyronine, and thyrotropin concentrations during acute nonthyroidal illness and recovery in dogs.

Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03-0.65] vs 0.11 ng/mL [range (0.05-0.26)], mean difference = 0.09 ng/mL; P = .03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs.

Effect of recombinant human thyroid stimulating hormone on radioactive iodine uptake by thyroid carcinoma in dogs.

The high doses of radioiodine-131 (131I) and, subsequently, the high radioactive burden for dog and environment warrants optimization of 131I therapy in dogs with thyroid carcinoma (TC). To evaluate the effect of a revised protocol with recombinant human thyroid stimulating hormone (rhTSH) on tumor radioactive iodine uptake (RAIU) in dogs with TC. Nine client-owned dogs diagnosed with TC. A prospective cross-over study in which tumor RAIU was calculated and compared at 8 hours (8h-RAIU) and 24 hours (24h-RAIU) after injection of radioactive iodine-123 (123I), once with and once without rhTSH (ie, 250 μg, IM, 24 and 12 hours before 123I) in each dog. Simultaneously, serum total thyroxine (TT4) and TSH were measured at baseline (T0), and 6 (T6), 12 (T12), 24 (T24), and 48 hours (T48) after the first rhTSH administration. Tumor RAIU was significantly higher at 24 hours with rhTSH compared to no rhTSH (mean difference = 8.85%, 95% CI of [1.56; 16.14]; P = .03), while this was non-significant at 8 hours (mean difference = 4.54%, 95% CI of [0.35; 8.73]; P = .05). A significant change of serum TT4 (median difference T24 - T0 = 35.86 nmol/L, interquartile range [IQR] = 15.74 nmol/L) and TSH (median difference T24 - T0 = 1.20 ng/mL, IQR = 1.55 ng/mL) concentrations occurred after administration of rhTSH (P < .001). Recombinant human TSH could optimize 131I treatment in dogs with TC by increasing tumor RAIU and thus 131I treatment efficacy.

Mice Lacking α-Actinin-1 in Megakaryocytes Display the Feature of Thrombocytopenia and Impair Platelet Functions

Cytoskeleton remodeling and mitochondrial bioenergetics play important roles in platelet biogenesis and functions. α-Actinin-1, a filament crosslinker, was widely expressed in nonmuscle cells, including megakaryocytes (MKs) and platelets. The cytoskeleton is essential for normal mitochondrial morphology, motility, and distribution. In recent years, the accumulated evidence suggests that inherited mutations in α-actinin-1 are implicated in congenital macrothrombocytopenia. However, the role and underlying mechanism of α-actinin-1 in platelet biogenesis and platelet functions remain poorly studied. In this study, we generated an MK-specific α-actinin-1 knockout mouse model (referred to herein as PF4- Actn1-/-) to investigate the contribution of α-actinin-1 in platelet biogenesis and functions. Blood count tests showed that PF4- Actn1-/- mice exhibited reduced platelet counts. The decreased platelet number in PF4- Actn1-/- mice was not attributed to accelerated platelet clearance or impaired TPO generation in vivo. Platelet count changes observed in an anti-GPIbα antibody-induced thrombocytopenia model and splenectomy indicated that the diminished platelet counts in PF4- Actn1-/- mice might be due to defects in platelet biogenesis. Compared to control mice, PF4- Actn1-/- mice had normal numbers of MK progenitors, including in LSK, MPP, CMP, GMP, MEP, and PreMegE. H&amp;E staining and flow cytometry revealed a decrease in the number of MKs in BM, but an increase in the number of MKs in the spleen. The absence of α-actinin-1 significantly increased the proportion of 2N-4N MKs and decreased the proportion of 8N-32N MKs. CFU-MK colony formation and MK migration in response to SDF-1 signaling was inhibited in PF4- Actn1-/- mice. Furthermore, in vitro studies showed a reduced ratio of PPF-bearing MKs in fetal liver-derived PF4- Actn1-/- MKs. Collectively, these data suggest that α-actinin-1 deficiency in mouse MKs could impair platelet biogenesis, resulting in thrombocytopenia in PF4- Actn1-/- mice. Platelet adhesion and spreading on immobilized fibrinogen and collagen, thrombin-stimulated clot retraction, and platelet aggregation in response to various concentrations of ADP, thrombin, and collagen was significantly decreased in PF4- Actn1-/- platelets. PF4- Actn1-/- platelets also exhibited decreased integrin αIIbβ3 activation and reduced P-selectin exposure in response to various concentrations of ADP, ADP+EPI, thrombin, collagen, and convulxin. Notably, PF4- Actn1-/- platelets showed inhibited calcium mobilization, reactive oxygen species (ROS) generation, and actin polymerization in response to collagen and thrombin. Furthermore, PF4- Actn1-/- mice demonstrated significantly impaired hemostasis. No differences were observed in the PT, APTT, TT, and fibrinogen concentrations between PF4- Actn1-/- mice and Actn1f/f mice. However, tail, liver, and brain bleeding tests revealed that PF4- Actn1-/- mice had significantly prolonged bleeding time and increased bleeding volume. Kaolin-activated whole thromboelastography (TEG) mapping assay indicated that there were no differences in the R-time, K-time, and α-angle values, but the maximum amplitude was decreased in PF4- Actn1-/- mice. To explore the mechanism of α-actinin-1 in platelet biogenesis and platelet functions. Low- (2-4N) and high-ploidy (≥8N) Actn1f/f and PF4- Actn1-/- MKs were sorted for quantitative proteomics analysis. The results of 4D label-free quantitative proteomics revealed that protein expression was significantly decreased in high-ploidy MKs following α-actinin-1 knockdown. Functional enrichment analysis of differentially expressed proteins indicated that α-actinin-1 deletion reduced platelet activation and mitochondrial functions. PF4- Actn1-/- platelets exhibited reduced mitochondrial membrane potential, mitochondrial ROS generation, mitochondrial respiration and glycolysis, suggesting alterations in mitochondrial function in platelets. In this study, we report that mice with α-actinin-1 deficiency in MKs recapitulate the features of thrombocytopenia and exhibit impaired platelet functions.

A-053 Poor Clinical Utility of Free and Bioavailable Testosterone is Underscored by Overutilization

Abstract Background Symptomatic androgen deficiency has an estimate prevalence of 2%–12% in males over 40 years of age and is associated with several comorbidities such as hypertension, obesity, dyslipidemia, metabolic syndrome, diabetes, and COPD. Diagnosis relies heavily on the measurement of testosterone concentrations. While total testosterone (tT) is often sufficient to diagnose deficiency, free testosterone (fT) or bioavailable testosterone (baT; non-sex hormone binding globulin (SHBG)-bound) may be helpful in assessing patients with suspected hormone binding abnormalities. Consensus guidelines recommend relying on tT measurement and only using fT or baT testing when indicated. Despite these recommendations, requests for measured fT and baT account for a large percentage of testosterone orders in our institution. Here we examined the utilization of testosterone orders, assessed the clinical utility of measured fT and baT relative to tT alone, and devised a reflex algorithm to optimize fT and baT utilization. Methods Testosterone data was collected over a 12 month period, September 2020–August 2021. Only data from adult males with established reference intervals was included in the final cohort; ≥20 and 20–69 years of age for fT and baT, respectively. Logistic regression was used to determine the probability of low fT and baT based on tT concentration. An algorithm based on initial tT concentration was established to reflex to fT/baT when most likely to provide additional benefit. Results Of 9754 testosterone tests performed on male patients during the study period, 4514 (46%) included a measured fT and/or baT. After excluding data without established reference intervals, the final cohort consisted of 1851 fT and 2514 baT measurements. Overall concordance with tT was 70.0% and 74.8% for fT and baT, respectively. However, only 0.2% (3/1479) were found to have low fT and 8.4% (166/1988) low baT when tT was greater than the reference interval lower limit (i.e., normal or high). The probability of a patient having low fT or baT with normal tT peaked at 0.01 and 0.21, respectively, and was greatest at the tT reference interval lower limit (240 ng/dL). An algorithm was devised in which only samples with tT concentrations of 240–500 ng/dL would reflex to baT testing. In this cohort, 90% of discordant (low baT with normal tT) samples would have triggered the baT reflex while reducing the overall utilization of baT by 55%. Applying the same reflex algorithm would have also reflexed 100% of discordant fT samples. Conclusions Despite being performed with nearly half of all testosterone orders, baT, and especially fT, provided little additional clinical utility to tT alone. By determining the probability of a low baT or fT when Tt is above the reference interval lower limit, a reflex algorithm can be devised to help optimize baT and fT utilization. While this algorithmic approach has been proposed by others, the reflex values in our cohort differ significantly from previously published values suggesting that laboratories should determine limits based on their individual testosterone assays. The logistic regression method utilized here provides one such example laboratories can follow for undertaking such an analysis.

A-048 Accurate Measurement of Free Testosterone in Serum using Equilibrium Dialysis Coupled with ID-UHPLC-MS/MS

Abstract Background Assessment of free testosterone (FT) has been recommended in recent clinical practice guidelines as a biomarker for diagnosis and management of testosterone related disorders such as male testosterone deficiency due to hypogonadism and female androgen excess due to polycystic ovary syndrome (PCOS). FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques. Though the ED approach is recognized as the recommended approach, it is laborious and technically challenging for routine clinical use. The CDC Clinical Standardization Program is developing a high throughput automated method using the ED procedure coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ID-UHPLC-MS/MS) that is suitable for routine patient care and large-scale epidemiologic studies. Methods Serum samples are dialyzed in a custom-designed multi-well plate against a protein-free HEPES buffer (pH 7.4) at 37 °C until equilibrium. After isolating endogenous FT from protein-bound testosterone by ED, isotope-labeled internal standard (13C3-testosterone) was added to the dialysate for quantification. Certified pure primary reference material (National Measurement Institute-M914) was used to prepare calibrators, enabling traceability and ensuring measurement trueness. FT was further isolated from the dialysate matrix using supported liquid extraction and a chromatographic separation from interfering compounds and quantitation by tandem MS. Results The measurement ranges covered 0.2–1000 ng/dL for testosterone, with the bias within ±5% and precision less than 10% CV. A total of 45 samples with a wide range of total testosterone (TT, 21–912 ng/dL) and SHBG (11–129 nmol/L) were analyzed and showed the suitability of this assay to measure the serum free testosterone levels in normal, hypogonadal males as well as in the majority of normal females and females with androgen excess. The application of 48-well format plate and automated liquid handler system significantly improves the throughput of sample preparation. In addition, comparison of the TT results measured with the presented TT method with calculated TT concentrations, suggest that on average calculation overestimates TT concentration by 34%. Conclusion The described high throughput method for FT allows for sufficiently accurate and precise measurement for routine applications including large epidemiologic studies to help with establishing reference intervals.

Polychlorinated biphenyls and thyroid function: a scoping review.

Numerous evidence indicates the association between polychlorinated biphenyls (PCBs), an endocrine disrupter, with thyroid hormone disruption, contradictory findings also exist. Herein, we tried to address this question by performing a scoping review. The search was performed on PubMed, Scopus, Web of Science, and Google Scholar databases from 2010 onwards. Animal studies on PCBs' effect on thyroid function were searched. The SYRCLE's RoB scale assessed the risk of bias. I2 and Q tests are used for investigating heterogeneity. A random-effects model with the pooled standard means difference (SMD) and 95% confidence interval (CI) was performed for the TSH, TT4, TT3, and FT4 outcomes using Comprehensive Meta-Analyses (CMA) Software version 3. Also, we conducted subgroup analyses based on the different types of PCB. The initial search identified 1,279 publications from the main databases 26 of them fulfilled our eligibility criteria for the study, and then five studies among selected studies had sufficient data for analysis. Meta-analysis of data revealed that Aroclor 1260 (SDM: -0.47, 95% CI: -0.92, -0.01, p=0.044) and PCB 126 (SDM: 0.17, 95% CI: -0.40, 0.75, p=0.559) significantly increased TSH concentration in the exposed groups vs. the control groups. Related to the effects of PCBs on the TT4, our findings indicated a significant reduction the TT4 concentration of animals exposed to Aroclor 1260 (SDM: -5.62, 95% CI: -8.30, -2.94, p=0.0001), PCB 118 (SDM: -6.24, 95% CI: -7.76, -4.72, p=0.0001), PCB 126 (SDM: -1.81, 95% CI: -2.90, -0.71, p=0.001), and PCB 153 (SDM: -1.32, 95% CI: -2.29, -0.35, p=0.007) vs. the controls. Our meta-analysis indicated a significant increase in TT3 concentration following exposure to PCB 118 and PCB 153 (SDM: -0.89, 95% CI: -1.36, -0.42, p=0.0001, and SDM: -1.45, 95% CI: -2.15, -0.75, p=0.0001, respectively). Aroclor 1254 and PCB 126 significantly decreased TT3 concentration (SDM: 1.25, 95% CI: 0.29, 2.21, p=0.01 and SDM: 3.33, 95% CI: 2.49, 4.18, p=0.0001, respectively). PCB 126 significantly decreased FT4 in the exposed groups vs. the control groups (SDM: -7.80, 95% CI: -11.51, -5.35, p=0.0001). Our findings showed an association between PCBs exposure and hypothyroidism in rodents, fish, and chicken embryos. Regarding to the most evidence of hypothyroidism effects of PCBs in animal species, it is necessary to consider large cohort studies to address the association between PCBs exposure and thyroid function impairment in humans.

Adrenal response to ACTH challenge alters thyroid and immune function and varies with body reserves in molting adult female northern elephant seals.

Intrinsic stressors associated with life-history stages may alter the responsiveness of the hypothalamic-pituitary-adrenal axis and responses to extrinsic stressors. We administered adrenocorticotropic hormone (ACTH) to 24 free-ranging adult female northern elephant seals (NESs) at two life-history stages: early and late in their molting period and measured a suite of endocrine, immune, and metabolite responses. Our objective was to evaluate the impact of extended, high-energy fasting on adrenal responsiveness. Animals were blood sampled every 30 min for 120 min post-ACTH injection, then blood was sampled 24 h later. In response to ACTH injection, cortisol levels increased 8- to 10-fold and remained highly elevated compared with baseline at 24 h. Aldosterone levels increased 6- to 9-fold before returning to baseline at 24 h. The magnitude of cortisol and aldosterone release were strongly associated, and both were greater after extended fasting. We observed an inverse relationship between fat mass and the magnitude of cortisol and aldosterone responses, suggesting that body reserves influenced adrenal responsiveness. Sustained elevation in cortisol was associated with alterations in thyroid hormones; both tT3 and tT4 concentrations were suppressed at 24 h, while rT3 increased. Immune cytokine IL-1β was also suppressed after 24 h of cortisol elevation, and numerous acute and sustained impacts on substrate metabolism were evident. Our data suggest that female NESs are more sensitive to stress after the molt fast and that acute stress events can have important impacts on metabolism and immune function. These findings highlight the importance of considering life-history context when assessing the impacts of anthropogenic stressors on wildlife.

Effects of Quetiapine on Thyroid Function Tests in Schizophrenic Patients

To investigate the effects of quetiapine on thyroid function tests in newly diagnosed schizophrenic patients. Thirty subjects with schizophrenia, were treated openly with quetiapine .Diagnosis of schizophrenia was made according to DSM-IV criteria of American Psychiatric Association. Another thirty healthy individual participated in the study as a control group. Thyroid data, consisting of values for thyroid-stimulating hormone (TSH), total triiodothyronine (TT3 ), and total thyroxine (TT4). TSH, TT3, and TT4 were measured by radioimmunoassay. Measurements of patient’s thyroid data were done before and after 3 months of therapy (Suggested period of the research) with quetiapine and at the start of the research for the controls. Comparison of TSH, TT3 and TT4 of the control group and those of patients before treatment shows a non significant differences for all parameters. Comparison between TSH, TT3 and TT4 values before and after treatment with quetiapine shows only a significant reduction of TT4 values (P&lt;0.001). This study shows that 3 months therapy with quetiapine leads to a reduction of TT4 concentration in the serum of schizophrenic patients.

Mercury Bioaccumulation and Cortisol Interact to Influence Endocrine and Immune Biomarkers in a Free-Ranging Marine Mammal

Mercury bioaccumulation from deep-ocean prey and the extreme life history strategies of adult female northern elephant seals (Mirounga angustirostris) provide a unique system to assess the interactive effects of mercury and stress on animal health by quantifying blood biomarkers in relation to mercury (skeletal muscle and blood mercury) and cortisol concentrations. The thyroid hormone thyroxine (tT4) and the antibody immunoglobulin E (IgE) were associated with mercury and cortisol concentrations interactively, where the magnitude and direction of the association of each biomarker with mercury or cortisol changed depending on the concentration of the other factor. For example, when cortisol concentrations were lowest, tT4 was positively related to muscle mercury, whereas tT4 had a negative relationship with muscle mercury in seals that had the highest cortisol concentrations. Additionally, we observed that two thyroid hormones, triiodothyronine (tT3) and reverse triiodothyronine (rT3), were negatively (tT3) and positively (rT3) associated with mercury concentrations and cortisol in an additive manner. As an example, tT3 concentrations in late breeding seals at the median cortisol concentration decreased by 14% across the range of observed muscle mercury concentrations. We also observed that immunoglobulin M (IgM), the pro-inflammatory cytokine IL-6 (IL-6), and a reproductive hormone, estradiol, were negatively related to muscle mercury concentrations but were not related to cortisol. Specifically, estradiol concentrations in late molting seals decreased by 50% across the range of muscle mercury concentrations. These results indicate important physiological effects of mercury on free-ranging apex marine predators and interactions between mercury bioaccumulation and extrinsic stressors. Deleterious effects on animals' abilities to maintain homeostasis (thyroid hormones), fight off pathogens and disease (innate and adaptive immune system), and successfully reproduce (endocrine system) can have significant individual- and population-level consequences.

The associations between concentrations of gestational bisphenol analogues and thyroid related hormones in cord blood: A prospective cohort study

Animal studies indicated that Bisphenol analogues (BPs) exhibited potential thyroid toxicity. However, little is known of the associations between maternal BPs exposure and offspring’s thyroid related hormones in humans. On the basis of Shanghai-Minhang Birth Cohort study, we analyzed BPs in maternal urine collected at the third trimester of pregnancy. Thyroid related hormones (THs), including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured in cord blood samples. We performed multiple linear regression and Bayesian kernel machine regression (BKMR) models to explore the single and joint effects of gestational BPs exposure on thyroid related hormones in cord blood among 258 mother-child pairs. Statistically significant inverse associations of categorized BPA with FT3 and TT4 concentrations were observed. We also found a significant association between the mixture of BPs in maternal urine and increased concentration of TT3 in cord blood and a marginally significant association between BPs mixture and increased FT3 concentrations. Further associations of BPA with lower TT4/FT4 and of Bisphenol AF (BPAF) with higher TT3/FT3 were also suggestive, by BKMR model, when other BPs were fixed at 25th percentiles. It was concluded that prenatal BPs exposure was associated with THs in cord blood. Exposure to BPA and BPAF might have large contributions to the effects on thyroid function than other bisphenols.

Thyroid hormones in canine pregnancy and lactation

It is believed that thyroid function has a significant effect on fertility and fetal development in mammals. So far, however, only few studies have been published about potential effects of the reproductive cycle stage on thyroid hormone concentrations in dogs. Therefore, over the course of 122 pregnant and non-pregnant cycles in healthy bitches, Thyroid stimulating hormone (TSH), free Thyroxine (fT4), total Thyroxine (tT4) and Progesterone (P4) were measured six times to assess the influence of the cycle stage and pregnancy on hormone concentrations. The aim was to evaluate established reference intervals for the thyroid hormones in a female study population. Of the 122 bitches, 98 became pregnant. Blood samples were collected during estrus, three times in pregnancy, during lactation and after weaning, or at equivalent times during and after estrus in non-pregnant dogs. No differences between pregnant and non-pregnant animals in any of the thyroid hormones were found. Hormone concentrations, however, differed significantly between the six samplings (p < .01). TSH initially declined during pregnancy, then rose again. The mean concentration of all dogs exceeded the overall upper reference limit of 0.70 ng/mL during lactation. Concentrations of tT4 and ft4 increased during the first third of pregnancy and then subsequently declined. The overall reference limits for tT4 were 0.47–3.20 μg/dL, and for fT4 4.86–29.60 pmol/L, but the reference intervals varied between the sampling dates. The observed patterns may reflect that maternal tT4 and fT4 seem to have important effects during early pregnancy, including a pronounced negative feedback effect on TSH. The initial increase and subsequent decline of tT4 and fT4 concentrations during the course of pregnancy is in accordance with findings in humans and may support the development of fetal thyroid function. The observed peak of TSH concentrations during lactation suggests that the demand for thyroid hormones in this phase is largest. Even if the underlying causes and mechanisms of thyroid regulation are not fully understood, the results of this study show relevant changes of hormone concentrations in the course of the sexual cycle and pregnancy. In that regard, cycle stage needs to be considered when assessing thyroid function in bitches.

Laboratory indicators of hypothyroidism and TgAA-positivity in the Eurasian dog breed.

Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds. Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009-2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination. The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15-29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9-4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6-9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1-2.4%) and 2.1% (n = 32; 95% CI: 1.4-2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up. The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.

Association of the Manganese Superoxide Dismutase (Mn-SOD) Gene C47T Polymorphism with Lung Cancer: A Case-Control Study.

The objective of this study was to determine the association between manganese superoxide dismutase (Mn-SOD) gene C47 T polymorphism and the risk of malignant lung cancer in Iraqi smokers. Blood samples were obtained from 260 lung cancer patients (88 females and 172 males) and 295 healthy individuals (91 females and 204 males). DNA was extracted from blood samples and the SOD2 gene was amplified using specific primers. The nucleotide sequences of the SOD2 gene were analyzed by using BLAST server at National Center for Biotechnology Information (NCBI) and the Raptorx app. TT, CT, and CC genotypes concentrations were 48.1%, 33.2%, and 18.7%, respectively, in the control group. The concentrations of TT, CT, and CC genotypes were 43.5%, 31.5%, and 25%, respectively, in the case group. There were no statistical differences between cases and controls in terms of genotype frequency of SOD2C47T polymorphism. We observed that SOD2C47T polymorphism CT genotype did not increase the risk of lung cancer development compared to those with TT genotype (OR= 0.951, 95% CI = 0.648-1.396; P = 0.798). In addition, it was observed that CC genotype did not increase the risk of lung cancer development in comparison with TT genotype ( OR=0.673, 95% Cl=0.435-1.041: P=0.075). These results indicated that there was no association between SOD2C47T polymorphism and the risk of lung cancer development in Iraqi smokers.