Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (ß coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (ß coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by ß coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Introduction: Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. Aim: The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. Methods: This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Results: Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Conclusions: Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Plasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy.

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.

Elevated thyroid stimulating hormone and metabolic syndrome risk in patients with first-episode and drug-naïve major depressive disorder: a large-scale cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is common in major depressive disorder (MDD), but its relationship with thyroid hormones remains unclear. We aimed to examine the association of thyroid hormones and MetS in first-episode drug-naïve (FEDN) MDD patients. METHODS: We recruited 1718 unmedicated MDD patients in this cross-sectional study. MetS was defined based on the 2004 Chinese Diabetes Society Criteria. Serum thyroid hormones including free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb) were examined. We used the logistic regression model to determine risk factors for MetS and examined the performance of the regression model by using the Area Under the Curve (AUC). In addition, we performed the trend test to test whether the results were robust. RESULTS: The prevalence of MetS in unmedicated MDD patients was 34.4%. MDD patients with MetS had higher levels of serum TSH, TGAb, and TPOAb (all P < 0.001). Concurrently, serum TSH levels were independent risk factors for MetS in MDD patients (OR:1.49, 95%CI: 1.40-1.58), which could also distinguish MDD patients with and without MetS (AUC was 0.77). Additionally, in the trend test, the results also indicated a similar trend when TSH was used as a categorical variable (P for trend < 0.001). CONCLUSIONS: This study suggests that TSH levels were independent risk factors for MetS in FEDN MDD patients (OR:1.49). The examination of thyroid function may contribute to the early detection of MetS.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

The value of dynamic changes in FT3 level for predicting 90-day prognosis of HBV-ACLF patients.

OBJECTIVE: To explore the effect of dynamic changes in free triiodothyronine (FT3) level for predicting the 90 day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data of 122 hospitalised patients with HBV-ACLF between September 2018 and January 2020 were collected and divided into a survival group (77 cases) and a death group (45 cases) according to the 90 day prognosis. We statistically analysed the characteristics of FT3 changes in the two groups of patients. Binary logistic regression one-way analysis was used to assess the degree of influence of each factor. The Kaplan-Meier survival curve and receiver operating characteristic curve were used to evaluate the effect of a single change in FT3 level difference (single △FT3) and the FT3 level change range (△FT3 range) in predicting the 90-day prognosis of patients. RESULTS: There were only three types of changes in FT3 levels, which included 19 (15.6%) cases of continuous normal type, 35 (28.7%) cases of continuous decrease type and 68 (55.7%) cases of U-shaped change type. The difference in survival curves between the three types of patients was statistically significant (P < 0.001). CONCLUSION: The dynamic change type of FT3 is related to the disease severity and 90-day prognosis of patients with HBV-ACLF. The single FT3 value and FT3 range could be used as a predictive factor for the 90-day prognosis of patients with HBV-ACLF. These results have a degree of research value and are worth further exploration in the future.

Iopanoic acid alters thyroid hormone-related gene expression, thyroid hormone levels, swim bladder inflation, and swimming performance in Japanese medaka.

Disruption of the thyroid hormone system by synthetic chemicals is gaining attention owing to its potential negative effects on organisms. In this study, the effects of the dio-inhibitor iopanoic acid (IOP) on the levels of thyroid hormone and related gene expression, swim bladder inflation, and swimming performance were investigated in Japanese medaka. Iopanoic acid exposure suppressed thyroid-stimulating hormone ß (tshß), tshß-like, iodotyronin deiodinase 1 (dio1), and dio2 expression, and increased T4 and T3 levels. In addition, IOP exposure inhibited swim bladder inflation, reducing swimming performance. Although adverse outcome pathways of thyroid hormone disruption have been developed using zebrafish, no adverse outcome pathways have been developed using Japanese medaka. This study confirmed that IOP inhibits dio expression (a molecular initiating event), affects T3 and T4 levels (a key event), and reduces swim bladder inflation (a key event) and swimming performance (an adverse outcome) in Japanese medaka.

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

BACKGROUND: 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. OBJECTIVES: To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. ANIMALS: Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study.

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Variations in thyroid hormone levels in endangered St. Lawrence Estuary belugas: Potential linkage with stress and organohalogen contaminant exposure.

The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and their metabolites reverse T3 and 3,5-diiodothyronine [3,5-T2]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T4, rT3 and 3,5-T2. Specifically, there was a weak significant negative association between T4 and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T3 and Σ34PBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.

Impact of methimazole-induced hypothyroidism on postnatal swine.

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.

A Horizontal and Longitudinal Study on the Changes of Aging Thyroid Function in Elderly Male Population.

OBJECTIVES: There are few follow-up studies on thyroid function in the same group for many years. Therefore, the purpose of this study was to retrospectively analyze the changes of thyroid function in a group of people for 8 years and to explore the changes of thyroid function in elderly men with normal thyroid function with age. METHODS: Reviewing the records of elderly men who underwent physical examination in the Beijing Hospital physical examination center from 2013 to 2020, 354 subjects were included in the study. According to age, they are divided into 4 groups. The differences in thyrotropin (TSH), anti-triiodothyronine (rT3), free triiodothyronine (FT3), and free thyroid hormone (FT4) among different age groups in initial time (2013) were compared. Longitudinal comparison of changes of thyroid function in the same age group for 8 years was compared too. RESULTS: At the initial time, age was negatively correlated with FT3 (r = 0.349, p < 0.001), positively correlated with rT3 and TSH (r = 0.182, p < 0.001, r = 0.212, p < 0.001), but not correlated with FT4. The results of eight years of analysis show that, for TSH, during the whole follow-up period, the TSH of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The 70-79 age group was higher than the <60 years group at different time points, except for the age group <60 years. The other three groups showed an increasing trend with age, especially in the group of ≥80 years. For FT3, in 2013, the age ≥80 years group was significantly lower than that of the 70-79 years, 60-69 years, and <60 years old groups (p < 0.05). The analysis results at different time points in each age group showed a downward trend and then an upward trend. For FT4, there was no significant difference in FT4 among different age groups in 2013. Still, during the follow-up period, the age group ≥80 was lower than other age groups in 2019 and lower than the <60 years groups in 2014, 2015, 2019, and 2020, and the difference was statistically significant. The change rule of FT4 with the increase of age was not clear. For rT3, during the whole follow-up period, the rT3 of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The analysis results at different time points in each age group showed a trend of rising first, then falling, and finally rising. After 2017, the rT3 of the 70-79 years and ≥80 years groups increased with age. CONCLUSIONS: The thyroid function index of elderly men changes with age. In transverse analysis, the value of TSH is the highest, and FT3 is the lowest in the group ≥80 years old. There are differences between the changes in the longitudinal analysis and the results of the horizontal analysis. Therefore, the law of thyroid function changing with age in different individuals is not the same as that of the same individual with age, which should be paid more attention in medical research and clinical diagnosis and treatment.

Triiodothyronine Supplementation for Children Undergoing Cardiopulmonary Bypass: A Meta-Analysis.

Specific pediatric populations have exhibited disparate responses to triiodothyronine (T3) repletion during and after cardiopulmonary bypass (CPB). Objective: To determine if T3 supplementation improves outcomes in children undergoing CPB. We searched randomized controlled trials (RCT) evaluating T3 supplementation in children aged 0-3 years undergoing CPB between 1/1/2000 and 1/31/2022. We calculated Hazard ratios (HR) for time to extubation (TTE), ICU length of stay (LOS), and hospital LOS. 5 RCTs met inclusion criteria with available patient-level data. Two were performed in United States (US) and 3 in Indonesia with 767 total subjects (range 29- 220). Median (IQR) age 4.1 (1.6, 8.0) months; female 43%; RACHS-1 scores: 1-1%; 2-55%; 3-27%; 4-13%; 5-0.1%; 6-3.9%; 54% of subjects in US vs 46% in Indonesia. Baseline TSH and T3 were lower in Indonesia (p < 0.001). No significant difference occurred in TTE between treatment groups overall [HR 1.09 (CI, 0.94-1.26)]. TTE numerically favored T3-treated patients aged 1-5 months [HR 1.24 (CI, 0.97-1.60)]. TTE HR for the Indonesian T3 group was 1.31 (CI, 1.04-1.65) vs. 0.95 (CI, 0.78-1.15) in US. The ICU LOS HR for the Indonesian T3 group was 1.19 vs. 0.89 in US (p = 0.046). There was a significant T3 effect on hospital LOS [HR 1.30 (CI, 1.01-1.67)] in Indonesia but not in US [HR 0.99 (CI, 0.78-1.23)]. T3 supplementation in children undergoing CPB is simple, inexpensive, and safe, showing benefit in resource-limited settings. Differences in effects between settings likely relate to depression in baseline thyroid function often associated with malnutrition.

The paradox of spring: Thyroid and glucocorticoid responses to cold temperatures and food availability in free living Carneddau ponies.

In seasonal environments, maintaining a constant body temperature poses challenges for endotherms. Cold winters at high latitudes, with limited food availability, create opposing demands on metabolism: upregulation preserves body temperature but depletes energy reserves. Examining endocrine profiles, such as thyroid hormone triiodothyronine (T3) and glucocorticoids (GCs), proxies for changes in metabolic rate and acute stressors, offer insights into physiological trade-offs. We evaluated how environmental conditions and gestation impact on faecal hormone metabolites (fT3Ms and fGCMs) from late winter to spring in a free-living population of Carneddau ponies. Faecal T3Ms were highest in late February and March, when temperatures were lowest. Then, fT3Ms concentrations decreased throughout April and were at the lowest in May before increasing towards the end of the study. The decline in fT3M levels in April and May was associated with warmer weather but poor food availability, diet diversity and diet composition. On the other hand, fGCM levels did not display a clear temporal pattern but were associated with reproductive status, where pregnant and lactating females had higher fGCM levels as compared to adult males and non-reproductive females. The temporal profile of fT3Ms levels highlights metabolic trade-offs in a changing environment. In contrast, the ephemeral but synchronous increase in fGCM concentrations across the population suggest a shared experience of acute stressors (i.e., weather, disturbance or social). This multi-biomarker approach can evaluate the role of acute stressors versus energy budgets in the context of interventions, reproduction, seasonality and environmental change, or across multiple scales from individuals to populations.

Thyroid hormone concentrations in female baboons: Metabolic consequences of living in a highly seasonal environment.

How female mammals adapt metabolically in response to environmental variation remains understudied in the wild, because direct measures of metabolic activity are difficult to obtain in wild populations. However, recent advances in the non-invasive measurement of fecal thyroid hormones, triiodothyronine (T3), an important regulator of metabolism, provide an opportunity to understand how female baboons living in the harsh Amboseli ecosystem in southern Kenya adapt to environmental variability and escape strict reproductive seasonality. Specifically, we assessed how a female's activity budget, diet, and concentrations of fecal T3 metabolites (mT3) changed over the course of the year and between years. We then tested which of several environmental variables (season, rainfall, and temperature) and behavioral variables (female activity budget and diet) best predicted mT3 concentrations. Finally, we determined if two important reproductive events - onset of ovarian cycling and conception of an offspring - were preceded by changes in female mT3 concentrations. We found female baboons' mT3 concentrations varied markedly across the year and between years as a function of environmental conditions. Further, changes in a female's behavior and diet only partially mediated the metabolic response to the environment. Finally, mT3 concentrations increased in the weeks prior to menarche and cycling resumption, regardless of the month or season in which cycling started. This pattern indicates that metabolic activation may be an indicator of reproductive readiness in female baboons as their energy balance is restored.

Hypothyroidism and autoimmune thyroid disorders in rheumatoid arthritis: relationship with disease activity.

Background and aims: Thyroid function abnormalities and thyroid autoantibodies have previously been described in rheumatoid arthirits (RA) with limited data. In some studies, a relationship was found between thyroid autoantibodies and RA disease activity. However, there are not strong studies in the literature indicating the relationship between thyroid diseases and RA. The aim of this study was to determine the frequency of hypothyroidism and to investigate the relationship between thyroid hormone levels, autoantibodies and disease activity in patients with rheumatoid arthritis (RA). Methods : 1017 patients with the diagnosis of RA were recruited. This observational study was conducted between January 2014 and July 2015. Demographic variables were recorded. Anti-nuclear antibodies (ANA), anti-cyclic citrulli-nated peptide antibody (anti-CCP), Rheumatoid Factor (RF), C reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-microsomal antibody (anti-TPO )and anti-thyroglobulin antibody (anti-TG) were determined. Visual analog score and Disease Activiy Score 28 (DAS-28) ESR and DAS-28 CRP were recorded. The relationship between thyroid hormone levels and thyroid antibodies and disease activity parameters were determined. Results: 98 (%9,7) patients had hypothyroidism and 61 (%6) patients had hyperthyroidism. 210 (20,7%) patients with RA was positive for TPOAb and 165(16,3%) for anti-TG. Positive correlation was detected between anti-TPO positivity and anti-CCP levels (p:0.005, r:0,274). In anti-TG antibody positive patients, there was a significant positive correlation of thyroid hormone levels with CRP and DAS 28-CRP (p:0.01, r:0,120; p:0.01, r:0,169). Conclusion: Thyroid autoantibodies were found to be positive in 16-21% of patients with RA. Though hypothyroidism is not very frequent in RA patients, autoimmune thyroid disease is quite common, which may be related to disease activity.

Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Investigating the effect of combined use of selenium and Myo-inositol supplements on thyroid function and autoimmune characteristics in thyroid disorders: a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review the effect of selenium and inositol combination on thyroid function, autoimmune characteristics in thyroid diseases. RESEARCH DESIGN AND METHODS: To identify eligible studies, a systematic search was conducted in the PubMed/MEDLINE, Science-Direct, CINHAL, EMBASE, SCOPUS, Psychinfo, Cochrane, ProQuest, and Web of Science were searched using the main concepts, and all English-written articles that were published between 2007 and 2022 and had an available full text were examined. RESULTS: The data analysis of this research revealed that after the simultaneous use of selenium and inositol supplements, the level of Triiodothyronine(T3) increased by 0.105 in patients with thyroid disorders although this increase was not significant (P-value: 0.228). The level of Thyroxine (T4) significantly increased by 0.06 (P-value: 0.04). Anti-Thyroid Peroxidase Antibody (TPOAb) titer decreased by 119.36%, which was not significant (P-value: 0.070). Finally, the level of Thyroid-stimulating hormone (TSH) decreased by 1.45%, which was a significant change (P-value: 0.001). CONCLUSION: It was observed that simultaneous use of selenium and inositol supplements did not change the T3 and TPOAb titer levels; however, it leads to a decrease in TSH and increase in T4 levels. Further studies are required due to the limited number of studies.