Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

OBJECTIVE: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. DESIGN: Cross-sectional study. PARTICIPANTS: Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. MEASUREMENTS: Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). RESULTS: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). CONCLUSION: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Current utility of first-line FT4 and TSH in screening for central hypothyroidism.

BACKGROUND: Thyroid testing strategies vary across laboratories. First-line combined thyroid stimulating hormone (TSH) and freeT4 (FT4) have historically been preferred by many laboratories as this detects individuals with undiagnosed central hypothyroidism who can be missed with a first-line TSH-only strategy. However, an up-to-date evaluation of the utility of this approach is lacking. OBJECTIVES: We investigated the clinical utility of first-line TSH and FT4 in the detection of central hypothyroidism in current day practice. DESIGN, PATIENTS, AND MEASUREMENTS: The All-Wales laboratory information system was queried to identify thyroid function tests in patients aged ≥16 years with decreased FT4 and inappropriate TSH (low-FT4). The 1-year incidence of low-FT4 was determined using mid-year population data. Clinical information of patients with low-FT4 was reviewed to determine causes of low-FT4 and the incidence of central hypothyroidism. RESULTS: The incidence of low-FT4 varied according to FT4 assay method (range: 98-301 cases/100,000 population/year). Fifteen new cases of central hypothyroidism were detected in two health boards, equivalent to 2 cases/100,000 population/year. Positive predictive value of low-FT4 for central hypothyroidism was 2%-4%. In a cross-section of primary care patients, low-FT4 was detected in 0.5% of all thyroid tests with assay-related differences in detection rates. CONCLUSIONS: Although low-FT4 is a common laboratory finding, the incidence of central hypothyroidism remains rare. With the currently increased rates of thyroid testing and increased use of medications that decrease FT4, low-FT4 has a much lower predictive value for central hypothyroidism than previously reported. Thyroid screening strategies will need to balance the yield from first line TSH and FT4 testing with the cost of investigating individuals with non-pathological laboratory abnormalities.

Early identification of postoperative remission for thyrotropin-secreting adenomas.

OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study.

PURPOSE: Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study. METHODS: Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates. RESULTS: Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029-1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy. CONCLUSIONS: This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Neural thyroid hormone metabolism integrates seasonal changes in environmental temperature with the neuroendocrine reproductive axis.

We asked if environmental temperature alters thyroid hormone metabolism within the hypothalamus, thereby providing a neuroendocrine mechanism by which temperature could be integrated with photoperiod to regulate seasonal rhythms. We used immunohistochemistry to assess the effects of low-temperature winter dormancy at 4 °C or 12 °C on thyroid-stimulating hormone (TSH) within the infundibulum of the pituitary as well as deiodinase 2 (Dio2) and 3 (Dio3) within the hypothalamus of red-sided garter snakes (Thamnophis sirtalis). Both the duration and, in males, magnitude of low-temperature dormancy altered deiodinase immunoreactivity within the hypothalamus, increasing the area of Dio2-immunoreactivity in males and females and decreasing the number of Dio3-immunoreactive cells in males after 8-16 weeks. Reciprocal changes in Dio2/3 favor the accumulation of triiodothyronine within the hypothalamus. Whether TSH mediates these effects requires further study, as significant changes in TSH-immunoreactive cell number were not observed. Temporal changes in deiodinase immunoreactivity coincided with an increase in the proportion of males exhibiting courtship behavior as well as changes in the temporal pattern of courtship behavior after emergence. Our findings mirror those of previous studies, in which males require low-temperature exposure for at least 8 weeks before significant changes in gonadotropin-releasing hormone immunoreactivity and sex steroid hormones are observed. Collectively, these data provide evidence that the neuroendocrine pathway regulating the reproductive axis via thyroid hormone metabolism is capable of transducing temperature information. Because all vertebrates can potentially use temperature as a supplementary cue, these results are broadly applicable to understanding how environment-organism interactions mediate seasonally adaptive responses.

The influence of gender-specific factors influencing severe anxiety in psychotic major depression: role of thyroid hormones and depression severity.

BACKGROUND: Psychotic major depression (PMD) is characterized by major depressive disorder (MDD) accompanied by delusions or hallucinations. While the prevalence of PMD and its association with anxiety have been studied, gender-specific differences and the role of thyroid hormones in PMD-related anxiety remain less explored. METHODS: A total of 1718 first-episode and drug-naïve MDD patients was assessed for the presence of PMD and severe anxiety. Clinical assessments, including Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions-Severity (CGI-S) scale, were conducted to assess depression, anxiety, psychotic symptoms, and clinical severity, respectively. Blood samples were collected to measure thyroid function parameters. RESULTS: The prevalence of severe anxiety was higher in PMD patients compared to non-psychotic MDD patients (71.3% vs. 5.3%). No significant gender differences were observed in the prevalence of severe anxiety among PMD patients. However, elevated thyroid-stimulating hormone (TSH) levels and increased depression severity (HAMD scores) were identified as independent risk factors for severe anxiety in female PMD patients. In contrast, no significant risk factors were found in male PMD patients. The area under the receiver operating characteristic (AUCROC) analysis revealed that the HAMD score and TSH level showed acceptable discriminatory capacity for distinguishing between female PMD patients with and without severe anxiety. CONCLUSION: This study highlights the heightened prevalence of severe anxiety in PMD patients, with TSH levels and depression severity emerging as gender-specific risk factors for anxiety in females. These findings suggest the importance of thyroid hormone assessment and tailored interventions for managing anxiety in female PMD patients.

Seasonality of Reproduction in a Subtropical Free-Living Finch Amandava amandava: Plasticity of Adenohypophyseal Gonadotropes, Lactotropes, and Thyrotropes.

INTRODUCTION: This study sought to decipher the mechanism of transitions between life-history stages in a seasonally reproducing subtropical finch, Amandava amandava delineating the plasticity of the gonadotropes (LH cells), lactotropes (PRL cells), and thyrotropes (TSH cells) in the pituitary gland including the pars tuberalis, with regard to the in situ expression, morphological characteristics, and alteration in the plasma levels of hormones. METHODS: Immunohistochemistry of LH, PRL, TSH cells, morphometry and densitometry of expressed hormones (Image J software analysis), and ELISA for plasma hormonal levels were performed. RESULTS: LH, PRL, and TSH cells showed remarkable plasticity during the annual seasonal reproductive cycle. In the PT, all the 3 cell types were detected during the breeding phase, with additional detection of the TSH immunoreactivity during the pre-breeding and the PRL immunoreactivity during post-breeding phases. Pars distalis (PD) expressions and the plasma levels of the LH and TSH were at the peak during the breeding phase, but the PRL peak was during the post-breeding phase. In addition to PRL in the neurohypophysis and in the median eminence, hypothalamic PRL, and TSH were also elucidated. CONCLUSIONS: This study suggests activation of the gonadal axis by the PT TSH which might transduce seasonal cues, but not specifically photoperiod, in the birds of the tropics/subtropics. Post-breeding phase sustained high plasma TSH and peak plasma PRL might coordinate the transition to the non-breeding phase including the trigger of parental care as the later hormone assigned with. Hypothalamic TSH and PRL might influence events of seasonality through central modulation.

Changes in thyroid hormones predict weight regain in patients with obesity who undergo metabolic surgery.

AIM: To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. METHODS: This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. RESULTS: The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. CONCLUSIONS: Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Periodontitis and thyroid function: A bidirectional Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Previous studies suggest interaction between periodontitis and thyroid function, while the causality has not yet been established. We applied the Mendelian randomization (MR) method to assess bidirectional causal association between periodontitis and thyroid-related traits, including free thyroxine (FT4), thyroid stimulating hormone (TSH), hypothyroidism, hyperthyroidism and autoimmune thyroid disease (AITD). METHODS: Genetic instruments were extracted from large-scale genome-wide association studies on normal-range FT4 (N = 49 269) and TSH (N = 54 288) levels, TSH in full range (N = 119 715); hypothyroidism (discovery/replication cohorts: N = 53 423/334 316), hyperthyroidism (discovery/replication cohorts: N = 51 823/257 552), AITD (N = 755 406) and periodontitis (N = 45 563). Here, the inverse variance weighted (IVW) method was applied as the primary analysis, and robustness of results were assessed by several pleiotropic-robust methods. Results were adjusted for Bonferroni correction thresholds with significant p < .004 (0.05/13) and suggestive p between .004 and .05. RESULTS: The IVW analysis revealed a suggestively causal linkage between genetic predisposition to periodontitis and the increased risk of hypothyroidism (discovery cohort: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.05-1.46, p = .012; replication cohort: OR = 1.06, 95% CI = 1.01-1.11, p = .011). No evidence was found for supporting the impact of periodontitis on hyperthyroidism and AITD risks (associated p ≥ .209), as well as thyroid-related traits on periodontitis risk (associated p ≥ .105). These findings were robust and consistent through sensitivity analysis with other MR models. CONCLUSION: This bidirectional MR reveals periodontitis should not be attributed to variations in thyroid function but it has potential causal effect on hypothyroidism risk, which provides a better understanding of the relationship between periodontitis and thyroid function, and potential evidence for the clinical intervention of hypothyroidism. Further investigations are warranted to elucidate the nature and underlying mechanisms of this finding.

Association between maternal age and sex-based neonatal free triiodothyronine levels.

BACKGROUND: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. OBJECTIVE: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. METHODS: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. RESULTS: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. CONCLUSION: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function.

Correlation between thyroid hormone sensitivity and the risk of polycystic ovary syndrome.

OBJECTIVE: There has been some confusion in earlier research on the connection between thyroid function and polycystic ovary syndrome (PCOS). This research is aimed to probe into the correlation between thyroid condition and the risk of PCOS from a new standpoint of thyroid hormone sensitivity. METHODS: This research comprised 415 females with PCOS from Drum Tower Hospital Affiliated with the Medical School of Nanjing University, and 137 non-PCOS individuals were selected as the normal control. Based on free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH), we calculated the thyroid hormone sensitivity indices, which consist of Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI) and Free Triiodothyronine /Free thyroxine (FT3/FT4). The binary logistic regression model was adopted to investigate the correlation between thyroid hormone sensitivity indices with the risk of PCOS. Pearson or Spearman correlation analysis was employed to explore the association among thyroid-related measures with metabolic parameters in PCOS. RESULTS: Results of this research showed that females with PCOS had rising TFQI, TSHI, TT4RI, and FT3/FT4 levels compared with the control group. After adjustment for the impact of various covariates, there was no significant correlation between FT3/FT4 and the risk of PCOS; However, the odds ratio of the third and fourth vs. the first quartile of TFQI were 3.57(95% confidence interval [CI]:1.08,11.87) and 4.90(95% CI:1.38,17.38) respectively; The odds ratio of the fourth vs. the first quartile of TSHI was 5.35(95% CI:1.48,19.37); The odds ratio of the second vs. the first quartile of TT4RI was 0.27(95%CI 0.09,0.82). In addition, no significant correlation was observed between thyroid-related measures and metabolic measures in females with PCOS. CONCLUSIONS: A reduction in the sensitivity of central thyroid hormone is closely correlated with a higher risk of PCOS. Further research is necessary to corroborate our findings and the supporting mechanisms.

Thyroid function spectrum in Cushing's syndrome.

PURPOSE: Thyroid disorders have been reported in hypercortisolism patients. Endogenous Cushing's syndrome (CS) potentially complicates its metabolic sequelae. We investigated thyroid function in CS patients to determine this relationship. METHODS: In this cross-sectional study, we screened CS patients from 2016 to 2019 at our hospital. Patient demographic, medical history, and laboratory data were collected. Additionally, we performed a meta-analysis to demonstrate the prevalence of thyroid dysfunction in patients with CS. RESULTS: Among 129 CS patients, 48.6% had triiodothyronine (TT3), 27.9% had thyroxine (TT4), 24.6% had free T3 (FT3), 27.7% had free T4 (FT4), and 6.2% had thyroid-stimulating hormone (TSH) levels below the reference values. Those with clinical CS showed more pronounced thyroid suppression than did those with subclinical CS. Cortisol levels were markedly greater in patients with pituitary hypothyroidism (P < 0.001). Serum cortisol levels throughout the day and post low-dose dexamethasone-suppression test (LDDST) results correlated with thyroid hormone levels, particularly in ACTH-independent CS. Correlations varied by thyroid status; FT3 and TSH were linked to cortisol in euthyroid individuals but not in those with low T3 or central hypothyroidism. TSH levels notably halved from the lowest to highest cortisol tertile post-LDDST. Finally, meta-analysis showed 22.7% (95% CI 12.6%-32.9%) central hypothyroidism in 528 CS patients of nine studies. CONCLUSION: Thyroid hormone levels are significantly correlated with cortisol levels and are impaired in patients with CS. However, the physiological adaptation and pathological conditions need further study.

Association between multipollutant exposure and thyroid hormones in elderly people: A cross-sectional study in China.

Environmental chemicals have been indicated to cause disruption of thyroid homeostasis in human populations. However, previous studies mostly focused on single group of chemicals. Herein, we investigate the independent and combined effects of multiple pollutants on thyroid homeostasis, including thyroid-stimulating hormone (TSH), total and free thyroxine (tT4 and fT4) and total and free triiodothyronine (tT3 and fT3) in elderly people. These environmental pollutants (n = 144) are from ten categories, including phenols, parabens, perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), synthetic pyrethroids (SPs), herbicides, and metals. Few studies have evaluated the health risks of these 144 chemicals, especially their joint effects. In single-pollutant evaluations, multiple linear regression (MLR) models were used to estimate the independent associations between multiple exposures and thyroid biomarkers. In multi-pollutant evaluations, elastic net regression and Bayesian kernel machine regression (BKMR) models were used to estimate the combined associations. The MLR models showed that 41 chemicals were significantly related to THs levels. BKMR models revealed the most important chemical groups: metals for TSH, PAHs, SPs and PCBs for tT4, herbicides and SPs for tT3. This study will contribute to the understanding of multipollutant exposure and help prioritize specific chemical groups related to thyroid hormone disruption.

Associations between short-term exposure to air pollution and thyroid function in a representative sample of the Korean population.

BACKGROUND: Disruption of thyroid function can profoundly affect various organ systems. However, studies on the association between air pollution and thyroid function are relatively scarce and most studies have focused on the long-term effects of air pollution among pregnant women. OBJECTIVES: This study aimed to explore the associations between short-term exposure to air pollution and thyroid function in the general population. METHODS: Data from the Korea National Health and Nutrition Examination Survey (2013-2015) were analyzed (n = 5,626). Air pollution concentrations in residential addresses were estimated using Community Multiscale Air Quality models. The moving averages of air pollution over 7 days were set as exposure variables through exploratory analyses. Linear regression and quantile g-computation models were constructed to assess the effects of individual air pollutants and air pollution mixture, respectively. RESULTS: A 10-ppb increase in NO2 (18.8-µg/m3 increase) and CO (11.5-µg/m3 increase) was associated with 2.43% [95% confidence interval (CI): 0.42, 4.48] and 0.19% (95% CI: 0.01, 0.36) higher thyroid-stimulating hormone (TSH) levels, respectively. A 10-µg/m3 increase in PM2.5 and a 10-ppb increase in O3 (19.6-µg/m3 increment) were associated with 0.87% (95% CI: 1.47, -0.27) and 0.59% (95% CI: 1.18, -0.001) lower free thyroxine (fT4) levels, respectively. A simultaneous quartile increase in PM2.5, NO2, O3, and CO levels was associated with lower fT4 but not TSH levels. CONCLUSIONS: As the subtle changes in thyroid function can affect various organ systems, the present results may have substantial public health implications despite the relatively modest effect sizes. Because this was a cross-sectional study, it is necessary to conduct further experimental or repeated-measures studies to consolidate the current results.

Impaired sensitivity to thyroid hormones is associated with different grades of hypertension: A multicenter cross-sectional study.

BACKGROUND AND AIM: Accumulating evidence suggests a potential link between thyroid function with hypertension. However, the research results are limited, and there is no research to explore the relationship between central and peripheral thyroid hormones (THs) sensitivity and different grades of hypertension in patients with coronary heart disease (CHD). This study aims to prove the complex interaction between thyroid system and blood pressure, and provides new ideas for the assessment of hypertension in patients with CHD. METHODS AND RESULTS: Calculate parameters representing central and peripheral sensitivity to THs. Logistic regression analysis was used to analyze the relationship between central and peripheral THs sensitivity of CHD patients and different grades of hypertension, especially in different ages, sexes, blood glucose levels, smoking, and drinking statuses. Among the 34,310 participants, 19,610 (57.16 %) were diagnosed with hypertension. The risk of hypertension and TSHI (OR: 0.88; 95 % CI: 0.87-0.90; P < 0.001), TT4RI (OR: 0.998; 95 % CI: 0.998-0.999; P < 0.001), TFQI (OR: 0.63; 95 % CI: 0.60-0.67; P < 0.001), PTFQI (OR: 0.63; 95 % CI: 0.59-0.67; P < 0.001) was negatively associated. The risk of hypertension was positively associated with FT3/FT4 (OR: 1.20; 95 % CI: 1.17-1.22; P < 0.001). After stratified analysis, these associations remained significant at different ages, sexes, blood glucose levels, grades of hypertension, smoking, and drinking statuses (P < 0.001). CONCLUSIONS: This study shows that the decrease in central THs sensitivity index and the increase in peripheral THs sensitivity index are associated with a higher risk of hypertension in CHD patients.

Non-linear relationship between TSH and psychotic symptoms on first episode and drug naïve major depressive disorder patients: a large sample sized cross-sectional study in China.

INTRODUCTION: Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. METHODS: A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. RESULTS: Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p < 0.05). Smoothing plots showed a nonlinear relationship between TSH and PD, with the inflection point of TSH being 4.94 mIU/L. On the right of the inflection point, for each unit increase in serum TSH level on the right side of the inflection point, the probability of PD increased substantially by 47% (OR = 1.47, 95% CI: 1.25 to 1.73, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 0.87, 95% CI: 0.67 to 1.14, p = 0.32). CONCLUSION: Our investigation showed a nonlinear TSH-PD relationship in FEDN MDD patients, thus contributing to effective intervention strategies for psychotic symptoms in depression patients.

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.