The Effect and Potential Mechanism Analysis of Growth Hormone-Secreting Pituitary Adenomas on Thyroid Function.

OBJECTIVE: Current studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone-secreting pituitary adenoma (GHPA). METHODS: This was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function. RESULTS: GH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor-binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA. CONCLUSION: The study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.

The Role of Thyroid Dysfunction in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Imbalances in thyroid hormones have been linked with Alzheimer's dementia. Several studies have reported an association between thyroid disorders, such as hyper- or hypothyroidism, with Alzheimer's disease. However, there remains no consensus about the precise role of thyroid dysfunction in Alzheimer's disease. In this study we systematically searched PubMed, Embase and Scopus for clinical studies which reported the prevalence of hyper- or hypothyroidism in people with Alzheimer's disease compared to controls. Meta-analysis was performed to compare thyroid disorder prevalence in Alzheimer's disease and controls. Subgroup analysis was performed to assess the clinical and subclinical thyroid dysfunction, separately. Seven studies, including 1189 people with Alzheimer's disease and 72711 controls, were included in our sample. Hypothyroidism was significantly more prevalent in Alzheimer's disease compared with controls (6.4% vs 2.4%, p=0.01). Subgroup analysis showed that clinical hypothyroidism was not significantly different between Alzheimer's disease compared to controls (10.0% vs 5.3%, p=0.35). There was no difference in the crude overall prevalence of clinical and subclinical hyperthyroidism in Alzheimer's disease versus controls (2.4 vs 1.9%, p=0.73). Our analyses revealed a higher prevalence of hypothyroidism in Alzheimer's disease. Whether this finding is explained by hypothyroidism being a risk factor for, or consequence of, Alzheimer's disease requires longitudinal analysis. Our review supports further work into a potential role for treatment of hypothyroidism in the prevention or delay of Alzheimer's disease.

Subclinical thyroid dysfunction and chronic kidney disease: a nationwide population-based study.

BACKGROUND: Chronic kidney disease (CKD) has a significant impact on global health. Studies have shown that subclinical thyroid dysfunction may be related to CKD, but the association between subclinical thyroid dysfunction and CKD in the general population is unclear. We aimed to evaluate the risk of CKD according to thyroid function status in a large cohort. METHODS: We analyzed data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 3,257 participants aged ≥ 19 years who underwent thyroid and kidney function assessments were included in this study. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or urine albumin-creatinine ratio ≥ 30 mg/g. The risk of CKD according to thyroid function status was assessed using logistic regression, adjusted for potential confounders. RESULTS: Overall, 6.7% of the participants had CKD. There were no significant differences in thyroid-stimulating hormone and free thyroxine levels between the groups with and without CKD. The proportion of participants with CKD was significantly different among the thyroid function status groups (p = 0.012) and tended to increase significantly in the following order: subclinical hyperthyroidism (1.5%), euthyroidism (6.6%), and subclinical hypothyroidism (12.6%) (p for trend < 0.001). Subclinical hypothyroidism was a significant risk factor for CKD, even after adjusting for sex, age, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, hypertension, low high-density lipoprotein cholesterol, elevated triglycerides, hyperglycemia, free thyroxine, and thyroid-peroxidase anibody (odds ratio 2.161, 95% confidence interval 1.032-4.527, p = 0.041). CONCLUSION: Subclinical hypothyroidism is an independent predictor of CKD in the general population.

Relationship of iodine excess with thyroid function in 6-year-old children living in an iodine-replete area.

Background: Adequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea. Methods: A total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient (< 100 µg/L), adequate (100-199 µg/L), more than adequate (200-299 µg/L), mild excessive (300-999 µg/L), and severe excessive (≥ 1000 µg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated. Results: The median TSH level was 2.3 µIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 µg/L, with higher levels in boys (684 µg/L vs. 545 µg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (ß = - 0.04, p = 0.032 for mild excess; ß = - 0.04, p = 0.042 for severe excess) and T3 levels (ß = - 8.12, p = 0.009 for mild excess; ß = - 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (ß = 0.04, p = 0.046). Conclusion: Excess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation.

How does Hashimoto's thyroiditis affect bone metabolism?

Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system and bone interact with each other, coined osteoimmunology. Hashimoto's thyroiditis (HT) is one of the most common chronic autoimmune diseases which is accompanied by lymphocytic infiltration. It shows elevating thyroid autoantibody levels at an early stage and progresses to thyroid dysfunction ultimately. Different effects exert on bone metabolism during different phases of HT. In this review, we summarized the mechanisms of the long-term effects of HT on bone and the relationship between thyroid autoimmunity and osteoimmunology. For patients with HT, the bone is affected not only by thyroid function and the value of TSH, but also by the setting of the autoimmune background. The autoimmune background implies a breakdown of the mechanisms that control self-reactive system, featuring abnormal immune activation and presence of autoantibodies. The etiology of thyroid autoimmunity and osteoimmunology is complex and involves a number of immune cells, cytokines and chemokines, which regulate the pathogenesis of HT and osteoporosis at the same time, and have potential to affect each other. In addition, vitamin D works as a potent immunomodulator to influence both thyroid immunity and osteoimmunology. We conclude that HT affects bone metabolism at least through endocrine and immune pathways.

Thyroid Function and COVID-19 Susceptibility and Its Severity: A Two-Sample Mendelian Randomization Study.

Several observational studies have confirmed the relationship between thyroid hormones and coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian randomization (MR) analysis based on the largest publicly available summary datasets. Summary statistics with 49 269 individuals for free thyroxine (FT4) and 54 288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [OR] = 0.818; 95% CI, 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95% CI, 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.

Sex-specific effects of fluoride and lead on thyroid endocrine function in zebrafish (Danio rerio).

Fluoride (F) and lead (Pb) are widespread pollutants in the environment. F and Pb affect the thyroid endocrine system, but the mechanism of action between F and Pb is still unclear. In this study, in order to evaluate the effects of F or/and Pb on histopathological changes, antioxidant indices, the levels of thyroid hormones (THs), and the expression of endocrine-related genes in zebrafish thyroid. One thousand and two hundred zebrafish (female:male = 1:1) were randomly divided into four groups: control group (C group), 80 mg/L F group (F group), 60 mg/L Pb group (Pb group), and 80 mg/L F + 60 mg/L Pb group (F + Pb group) for 45 d and 90 d. Histopathological sections showed a loss of glia and follicular epithelial hyperplasia in the thyroid gland after exposure to F and Pb. Oxidative stress in the thyroid was induced after F and Pb exposure. And each oxidation index was increased after F + Pb exposure. Combined F and Pb exposure aggravated the downregulation of thyroid hormones T3 and T4 compared to exposure alone. Furthermore, F and Pb exposure altered the expression of thyroid endocrine-related genes in a time-dependent manner. These results indicate that F and Pb can affect the endocrine system of thyroid by changing the tissue structure, antioxidant capacity, thyroid hormone secretion and the levels of endocrine-related genes in thyroid. F and Pb can also produce toxic effects on thyroid, but the degree of poisoning is different in different indicators, mainly for the additive effect between them. Additionally, males are more sensitive than females to F or Pb toxicity. However, the specific molecular mechanism of the effects of F and Pb on thyroid endocrine system needs to be further studied.

The Impact of Kohlrabi Sprouts on Various Thyroid Parameters in Iodine Deficiency- and Sulfadimethoxine-Induced Hypothyroid Rats.

Brassica sprouts, as the rich source of dietary glucosinolates, may have a negative effect on thyroid function. In this study, kohlrabi sprouts diet, combined with two models of rat hypothyroidism, was tested. TSH, thyroid hormones and histopathology analysis were completed with the evaluation of immunological, biochemical, haematological parameters, cytosolic glutathione peroxidase, thioredoxin reductase in the thyroid, and plasma glutathione peroxidase. A thermographic analysis was also adapted to confirm thyroid dysfunction. The levels of TSH, fT3 and fT4, antioxidant enzyme (GPX) as well as histopathology parameters remained unchanged following kohlrabi sprouts ingestion, only TR activity significantly increased in response to the sprouts. In hypothyroid animals, sprouts diet did not prevent thyroid damage. In comparison with the rats with iodine deficiency, kohlrabi sprouts diet decreased TNF-α level. Neither addition of the sprouts to the diet, nor sulfadimethoxine and iodine deficiency, caused negative changes in red blood cell parameters, glucose and uric acid concentrations, or kidney function. However, such a dietary intervention resulted in reduced WBC levels, and adversely interfered with liver function in rats, most likely due to a higher dietary intake of glucosinolates. Moreover, the possible impact of the breed of the rats on the evaluated parameters was indicated.

Impact of Thyroid Autoimmunity on Assisted Reproductive Technology Outcomes and Ovarian Reserve Markers: An Updated Systematic Review and Meta-Analysis.

Background: Thyroid autoimmunity (TAI) has a high prevalence among women of reproductive age. Investigating its possible impact on ovarian function and fertility is, thus, of utmost relevance. The aim of this systematic review and meta-analysis was to elucidate the effect of TAI on both assisted reproductive technology (ART) outcomes and ovarian reserve. Methods: This systematic review and meta-analysis was restricted to two groups of research articles investigating the association between TAI and: (1) autologous ART outcomes (i.e., fertilization rate [FR], implantation rate, clinical pregnancy rate [CPR], miscarriage rate, and live birth rate), (2) markers of ovarian reserve (i.e., anti-Müllerian hormone, basal follicle stimulating hormone, antral follicle count, and number of oocytes retrieved). Studies including women affected by overt hypo/hyperthyroidism were excluded. Relevant studies were identified by a systematic search in PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus, from database inception to May 1, 2022. Results: From a total of 432 identified publications, 22 studies were included in Group 1 and 26 studies in Group 2. The presence of TAI was associated with a higher risk of miscarriage (7606 participants, odds ratio [OR] 1.52, confidence interval [CI 1.14-2.01], p = 0.004, I2 = 53%), lower chance of embryo implantation (7118 participants, OR 0.72, [CI 0.59-0.88], p = 0.001, I2 = 36%), and live birth (11417 participants, OR 0.73, [CI 0.56-0.94], p = 0.02, I2 = 71%). These associations were no longer observed in a subgroup analysis of patients who exclusively underwent intracytoplasmic sperm injection (ICSI). The FR and CPR as well as the mean values of surrogate markers of oocyte quantity appeared not to be affected by TAI. Conclusions: This data synthesis suggest a higher risk of adverse ART outcomes in women with positive TAI. However, the reliability of these findings is hampered by the relatively low quality of the evidence and significant heterogeneity in many of the meta-analyses. The possible protective effect of ICSI is promising but should be confirmed in controlled prospective clinical trials. PROSPERO Registration ID: CRD42021236529.

A Predictive Role of Autoantibodies Against the Epitope aa168-183 of ENO1 in the Occurrence of Miscarriage Related to Thyroid Autoimmunity.

Objective: The aim of the research is to study the association between the serum levels of autoantibodies against one important epitope (168FMILPVGAANFREAMR183, designated as P6) of α-enolase (ENO1-P6Abs) and miscarriage among euthyroid females with thyroid autoimmunity (TAI). Methods: Anti-ENO1-P6 total IgG was investigated in 432 euthyroid women, and its four subclasses were analyzed in 184 euthyroid women. The serum FT4, TSH, TgAb, and TPOAb levels were determined using an electrochemiluminescence immunoassay. The serum ENO1-P6Ab and anti-protein disulfide isomerase A3 autoantibody (PDIA3Ab) levels were determined using an enzyme-linked immunosorbent assay. Results: The serum levels of anti-ENO1-P6 total IgG, IgG2, IgG3, and IgG4 were significantly higher in euthyroid TAI females than in non-TAI controls. Additionally, anti-ENO1-P6 total IgG and its 4 subtypes were all markedly higher in euthyroid TAI females with pregnancy loss than those without miscarriage. Moreover, logistic regression analysis showed that highly expressed anti-ENO1-P6 total IgG, IgG1, IgG2, and IgG3 subtypes in the serum were all independent risk factors for euthyroid TAI-related miscarriage, and its IgG1 was also for non-TAI-related abortion. According to the trend test, the prevalence of miscarriage was increased in a titer-dependent manner with the raised levels of serum anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subtypes among euthyroid TAI females. The receiver operating characteristic curve analysis of anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subclass expressions in the serum for miscarriage prediction in euthyroid TAI females exhibited that the total areas under the curves were 0.773 ± 0.041, 0.761 ± 0.053, 0.827 ± 0.043, and 0.760 ± 0.050, respectively (all P <0.0001). Their corresponding optimal cut-off OD450 values were 0.68 (total IgG), 0.26 (IgG1), 0.97 (IgG2), and 0.48 (IgG3), with sensitivities of 70.8, 87.5, 83.3, and 85.4%, and specificities of 70.8, 59.1, 77.3, and 56.8%, respectively. There was an additive interaction between serum anti-ENO1-P6 and anti-PDIA3 total IgGs on the development of miscarriage (RERI = 23.6, AP = 0.79, SI = 5.37). Conclusion: The highly expressed ENO1-P6Abs may be important risk factors for euthyroid TAI-related miscarriage. The serum levels of ENO1-P6Abs may become good predictive markers for pregnancy loss in euthyroid TAI females, especially its IgG2 subclass expression.

Maintaining the thyroid gland in mutant thyroglobulin-induced hypothyroidism requires thyroid cell proliferation that must continue in adulthood.

Congenital hypothyroidism with biallelic thyroglobulin (Tg protein, encoded by the TG gene) mutation is an endoplasmic reticulum (ER) storage disease. Many patients (and animal models) grow an enlarged thyroid (goiter), yet some do not. In adulthood, hypothyroid TGcog/cog mice (bearing a Tg-L2263P mutation) exhibit a large goiter, whereas adult WIC rats bearing the TGrdw/rdw mutation (Tg-G2298R) exhibit a hypoplastic thyroid. Homozygous TG mutation has been linked to thyroid cell death, and cytotoxicity of the Tg-G2298R protein was previously thought to explain the lack of goiter in WIC-TGrdw/rdw rats. However, recent studies revealed that TGcog/cog mice also exhibit widespread ER stress-mediated thyrocyte death, yet under continuous feedback stimulation, thyroid cells proliferate in excess of their demise. Here, to examine the relative proteotoxicity of the Tg-G2298R protein, we have used CRISPR-CRISPR-associated protein 9 technology to generate homozygous TGrdw/rdw knock-in mice in a strain background identical to that of TGcog/cog mice. TGrdw/rdw mice exhibit similar phenotypes of defective Tg protein folding, thyroid histological abnormalities, hypothyroidism, and growth retardation. TGrdw/rdw mice do not show evidence of greater ER stress response or stress-mediated cell death than TGcog/cog mice, and both mouse models exhibit sustained thyrocyte proliferation, with comparable goiter growth. In contrast, in WIC-TGrdw/rdw rats, as a function of aging, the thyrocyte proliferation rate declines precipitously. We conclude that the mutant Tg-G2298R protein is not intrinsically more proteotoxic than Tg-L2263P; rather, aging-dependent difference in maintenance of cell proliferation is the limiting factor, which accounts for the absence of goiter in adult WIC-TGrdw/rdw rats.

Analysis of thyroid function in Japanese patients with coronavirus disease 2019.

Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.

Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica.

BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (µg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (µg/g) and blood (MnB) (µg/L), and blood lead (PbB) (µg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. RESULTS: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: ß = -0.79 (95%CI = -1.51, -0.08) and ß = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (ß = 0.04 (95%CI = 0.00, 0.07 per 1 µg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DISCUSSION: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.

Thyroid Status and Brain Circulation: The Rotterdam Study.

CONTEXT: Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown. OBJECTIVE: We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly people. METHODS: This was a population-based study of 3 subcohorts of the Rotterdam Study, starting in 1989, 2000, and 2006. A total of 5142 participants (mean age, 63.8 years; 55.4% women), underwent venipuncture to measure serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/minute). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non)linear regression models. RESULTS: FT4 (in pmol/L) levels had an inverse U-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion than middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P nonlinearity = .002) was up to -2.44 mL (95% CI -4.31; -0.56). Higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to -2.46 µm, 95% CI -4.98; 0.05 for lower FT4). CONCLUSION: These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through suboptimal brain circulation that is potentially modifiable.

Environmental arsenic exposure and its toxicological effect on thyroid function: a systematic review.

OBJECTIVES: This study was performed to review epidemiological evidence related to Arsenic (As) effects on the thyroid function by focusing on the serum thyroid hormone concentration. CONTENT: As, one of the main pollutants, has been recognized as an endocrine-disrupting agent that may affect the function of thyroid as shown by experimental studies. SUMMARY: This systematic study indicates the association between As exposure and thyroid dysfunction. The studies have shown an association between serum and urine concentration of arsenic and thyroid dysfunction. Most of them reported the association between increase in the serum or urine As levels and decrease in the triiodothyronine (T3) and thyroxine (T4), and also elevation in the thyrotropic hormone (TSH) levels. OUTLOOK: Our findings related to the effects of As on the function of thyroid in humans are still limited and future studies should be done to address this question.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Thyroid Function and Risk of Anemia: A Multivariable-Adjusted and Mendelian Randomization Analysis in the UK Biobank.

CONTEXT: Thyroid dysfunction is associated with higher anemia prevalence, although causality remains unclear. OBJECTIVE: This study aimed to investigate the association between thyroid function and anemia. METHODS: This cross-sectional and Mendelian randomization study included 445 482 European participants from the UK Biobank (mean age 56.77 years (SD 8.0); and 54.2% women). Self-reported clinical diagnosis of hypothyroidism was stated by 21 860 (4.9%); self-reported clinical diagnosis of hyperthyroidism by 3431 (0.8%). Anemia, defined as hemoglobin level of < 13 g/dL in men and < 12 g/dL in women, was present in 18 717 (4.2%) participants. RESULTS: In cross-sectional logistic regression analyses, self-reported clinical diagnoses of hypo- and hyperthyroidism were associated with higher odds of anemia (OR 1.12; 95% CI, 1.05-1.19 and OR 1.09; 95% CI, 0.91-1.30), although with wide confidence intervals for hyperthyroidism. We did not observe an association of higher or lower genetically influenced thyrotropin (TSH) with anemia (vs middle tertile: OR for lowest tertile 0.98 [95% CI, 0.95-1.02]; highest tertile 1.02 [95% CI, 0.98-1.06]), nor of genetically influenced free thyroxine (fT4) with anemia. Individuals with genetic variants in the DIO3OS gene implicated in intracellular regulation of thyroid hormones had a higher anemia risk (OR 1.05; 95% CI, 1.02-1.10); no association was observed with variants in DIO1 or DIO2 genes. CONCLUSION: While self-reported clinical diagnosis of hypothyroidism was associated with higher anemia risk, we did not find evidence supporting a causal association with variation of thyroid function within the euthyroid range. However, intracellular regulation of thyroid hormones might play a role in developing anemia.