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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. Objective s : 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. [ABSTRACT FROM AUTHOR]

Aim: To weight the prognostic value of thyroid hormones in catastrophic acute‐on‐chronic liver failure (ACLF). Methods: A retrospective cohort (n = 635) and two prospective cohorts (n = 353, and 198) were enrolled in this study. The performance of a novel developed prognostic score was assessed from aspects of reliability, discrimination, and clinical net benefit. Results: Thyroid‐stimulating hormone (TSH) was identified to have the most potential as a prognostic predictor for hepatitis B virus‐related ACLF among thyroid hormones. The novel score (modified chronic liver failure–organ failure score [mCLIF‐OFs]) was developed with weighted TSH and other scored organs in the CLIF‐OFs using the retrospective cohort (n = 635). The predicted risk and observed probabilities of death were comparable across the deciles of mCLIF‐OFs (Hosmer–Lemeshow χ2 = 4.28, p = 0.83; Brier scaled = 11.9). The C‐index of mCLIF‐OFs (0.885 [0.883–0.887]) for 30‐day mortality was significantly higher than that of the CLIF‐OFs, chronic liver failure–sequential organ failure assessment score (CLIF‐SOFAs), CLIF‐C ACLFs, Model of End‐stage Liver Disease (MELD), and Child–Pugh (all p < 0.001). The absolute improvements of prediction error rates of the mCLIF‐OFs compared to the above five scores were from 19.0% to 61.1%. After the analysis of probability density function, the mCLIF‐OFs showed the least overlapping coefficients (27.9%) among the above prognostic scores. Additionally, the mCLIF‐OFs showed greater net benefit than the above five prognostic scores over a wide range of risk threshold of death. Similar results were validated in two prospective ACLF cohorts with HBV and non‐HBV etiologies. Conclusion: Weighted TSH portended the outcome of ACLF patients, which could be treated as a "damaged organ" of the hypothalamic–pituitary–thyroid axis. The novel mCLIF‐OFs is a reliable prognostic score with better discrimination power and clinical net benefit than CLIF‐OFs, CLIF‐SOFAs, CLIF‐C ACLFs, MELD, and Child–Pugh. [ABSTRACT FROM AUTHOR]

Objective: Prevalence of subclinical thyroid disease increases with age, but optimal detection and surveillance strategies remain unclear particularly for older men. We aimed to assess thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations and their longitudinal changes, to determine the prevalence and incidence of subclinical thyroid dysfunction in older men. Design, Participants and Measurements: Longitudinal study of 994 community‐dwelling men aged ≥70 years without known or current thyroid disease, with TSH and FT4 concentrations assessed at baseline and follow‐up (after 8.7 ± 0.9 years). Factors associated with incident subclinical thyroid dysfunction were examined by logistic regression and receiver operating characteristic analyses. Results: At baseline, 85 men (8.6%) had subclinical hypothyroidism and 10 (1.0%) subclinical hyperthyroidism. Among 899 men euthyroid at baseline (mean age 75.0 ± 3.0 years), 713 (79.3%) remained euthyroid, 180 (20.0%) developed subclinical/overt hypothyroidism, and 6 (0.7%) subclinical/overt hyperthyroidism. Change in TSH correlated with baseline TSH (r =.16, p <.05). Change in FT4 correlated inversely with baseline FT4 (r = −0.35, p <.05). Only higher age and baseline TSH predicted progression from euthyroid to subclinical/overt hypothyroidism (fully‐adjusted odds ratio [OR] per year=1.09, 95% confidence interval [CI] = 1.02‐1.17, p =.006; per 2.7‐fold increase in TSH OR = 65.4, CI = 31.9‐134, p <.001). Baseline TSH concentration ≥2.34 mIU/L had 76% sensitivity and 77% specificity for predicting development of subclinical/overt hypothyroidism. Conclusions: In older men TSH concentration increased over time, while FT4 concentration showed little change. Subclinical or overt hypothyroidism evolved in one fifth of initially euthyroid men, age and higher baseline TSH predicted this outcome. Increased surveillance for thyroid dysfunction may be justified in older men, especially those with high‐normal TSH. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid disorders and diabetes mellitus coexist and are prevalent endocrinopathies among adult population. Thyroid dysfunction contributes to metabolic imbalances, increase beta‐cell apoptosis and glucose intolerance. There is paucity of data and contradicting findings on how thyroid dysfunction influence glycaemic control. Therefore, we evaluated thyroid dysfunction and glycaemic control among Type 2 diabetes mellitus (T2DM) patients in Ghana. Methods: A comparative cross‐sectional study was conducted among 192 T2DM patients from Effia Nkwanta Regional Hospital. Three consecutive monthly fasting plasma glucose (FBG) and glycated haemoglobin (HbA1c) were analysed and the results were classified as, moderate hyperglycaemia (MH) (FBG = 6.1–12.0 mmol/L, HbA1c < 7%), severe hyperglycaemia (SH) (FBG ≥ 12.1 mmol/L, HbA1c > 7%) and good glycaemic controls (GC) (FBG = 4.1–6.0 mmol/L, HbA1c < 7%). Thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), body mass index (BMI) and other clinical parameters were measured. Data analysis was done using R language version 4.0.2 and p <.05 was considered statistically significant. Results: There were no significant differences in age (years) between patients in the various glycaemic groups (p =.9053). The overall prevalence of thyroid disorders was 7.8% among T2DM patients. The prevalence of thyroid disorders was higher in patients with SH (11.7%) followed by those with MH (7.5%) and then those with GC (5.4%). Serum levels of TSH and FT3/FT4 ratio were significantly lower in T2DM patients with SH compared to those with MH and the GC (p <.0001). However, FT4 was significantly higher in SH patients compared to the good glycaemic controls (p <.01). The first tertiles of TSH [aOR = 10.51, 95% CI (4.04–17.36), p <.0001] and FT3 [aOR = 2.77, 95% CI (1.11–6.92), p =.0290] were significantly and independently associated with increased odds of hyperglycaemia. Conclusion: The prevalence of thyroid dysfunction is high in T2DM and increases with hyperglycaemia. Reduced TSH and T3 may worsen glycaemic control. Periodic monitoring of thyroid function should be incorporated into management guidelines among T2DM patients in Ghana. [ABSTRACT FROM AUTHOR]

Background: Cats commonly develop thyroid disease but little is known about the long‐term biological variability of serum thyroid hormone and thyrotropin (thyroid‐stimulating hormone; TSH) concentrations. Objectives: We aimed to determine the long‐term biological variation of thyroid hormones and TSH in clinically healthy cats. Methods: A prospective, observational study was carried out. Serum samples for analysis of total thyroxine (T4, by radioimmunoassay [RIA] and homogenous enzyme immunoassay [EIA]), triiodothyronine (T3), free T4 (by dialysis), and TSH were obtained every 8 weeks for 1 year from 15 healthy cats, then frozen until single‐batch analysis. Coefficients of variation (CV) within individual cats (CVI) and among individual cats (CVG), as well as the variation between duplicates (ie, analytical variation [CVA]) were determined with restricted maximum likelihood estimation. The indices of individuality (IoI) and reference change values (RCVs) for each hormone were calculated. Results: Some thyroid hormones showed similar (total T4 by EIA) or greater (TSH) interindividual relative to intraindividual variation resulting in intermediate to high IoI, consistent with previous studies evaluating the biological variation of these hormones weekly for 5–6 weeks. By contrast, total T4 (by RIA) and free T4 had a low IoI. Total T3 had a high ratio of CVA to CVI; therefore, interindividual variation could not be distinguished from analytical variation. No seasonal variability in the hormones could be demonstrated. Conclusions: Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations for analytes with intermediate‐high IoI (total T4, TSH) for individual cats and applying RCVs to subsequent measurements. [ABSTRACT FROM AUTHOR]

Objective: Thyroid‐stimulating hormone (TSH) harmonization is effective in minimizing differences between the results of immunoassays in healthy subjects. However, the effectiveness of TSH harmonization in clinical practice has not been investigated. The aim of this study was to evaluate the instability of TSH harmonization in clinical practice. Methods: We compared the reactivities of four harmonized TSH immunoassays using combined difference plots of 431 patients. We selected patients with statistically significant deviations in TSH levels and analyzed their thyroid hormone levels and clinical characteristics. Results: The combined difference plots showed that one harmonized TSH immunoassay exhibited markedly different reactivity even after TSH harmonization compared with the other three immunoassays. Among 109 patients with mild‐to‐moderate elevation of TSH levels, we selected 15 patients with statistically significant deviations in TSH levels according to the difference plots of three harmonized TSH immunoassays, excluding one immunoassay that showed different reactivity. The thyroid hormone levels of three patients were misclassified as hypothyroidism or normal due to deviating TSH levels. In terms of clinical characteristics, these patients were in poor nutritional status and general condition, possibly due to their severe illness (e.g., advanced metastatic cancer). Conclusion: We have confirmed that TSH harmonization in clinical practice is relatively stable. However, some patients showed deviating TSH levels in the harmonized TSH immunoassays, indicating the need for caution, particularly in poorly nourished patients. This finding suggests the presence of factors that contribute to the instability of TSH harmonization in such cases. Further investigation is warranted to validate these results. [ABSTRACT FROM AUTHOR]

Aim: Thyroid dysfunction in infants born to mothers with Graves' disease (GD) is influenced by maternal factors including thyroid status, thyroid‐stimulating hormone (TSH) receptor antibody (TRAb) concentration and antithyroid drug use. Thyroid dysfunction during early life could affect growth and development later in life. The aim of this study is to evaluate thyroid function tests (TFTs), and long‐term growth and development of children born to mothers with GD. Methods: A retrospective chart review of children born to mothers with GD at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, between January 2000 and December 2019 was performed. Clinical data including age of children at enrolment, sex, gestational age, birthweight, maternal thyroid status, maternal TRAb level, maternal GD treatment during pregnancy, neonatal TSH screening and TFT results, and growth and development outcomes of children were collected. Results: There were 262 children (148 males) enrolled. Twelve (4%) infants had neonatal GD. Five (2%) infants had hypothyroidism requiring levothyroxine treatment: four had secondary hypothyroidism and one patient had congenital primary hypothyroidism. Seven (3%) infants had transient TSH elevation, which fell to normal by 2 weeks of age. The remaining 238 children had normal TFT results. Three out of 12 children with neonatal GD had either delayed growth or development. Conclusions: A number of infants born to mothers with GD had abnormal TFTs requiring specific management, and some of them had abnormal growth and development. Careful evaluation of TFTs and long‐term follow‐up are mandatory for those children. [ABSTRACT FROM AUTHOR]

Summary: Sleep is essential for the maintenance of health and systemic homeostasis. Decreased sleep time and sleep quality have been associated with a wide range of diseases. To evaluate the effects of obstructive sleep apnea (OSA) and total or selective rapid eye movement (REM) sleep deprivation on male reproductive function, we performed a three‐arm parallel study with one pre‐defined OSA group and a group of healthy volunteers who were then randomised into total or REM sleep deprivation groups. Questionnaires were completed and overnight polysomnography was undertaken, and blood and sperm samples were collected at the Sleep Institute, São Paulo, Brazil. OSA was diagnosed using questionnaires and polysomnography. Male sexual function was assessed through the questionnaires, blood tests, and semen samples. Data showed an association between OSA and lower circulating levels of total and free testosterone and high‐density lipoproteins, as well as a lower proportion of healthy sperm cells and decreased sperm concentration, in comparison to volunteers. Volunteers subjected to either total or REM sleep deprivation had increased circulating levels of thyroid‐stimulating hormone, insulin, and higher homeostatic model assessment of insulin resistance (HOMA‐IR) values. Both sleep‐deprived groups also shown decreased cholesterol, and low‐density lipoproteins when compared to their baseline levels, but had no alterations in their spermograms. We observed a reduction in total testosterone following total sleep deprivation, but no effect after REM sleep deprivation. OSA was associated with a hormonal imbalance, which is probably linked with impaired reproductive function and associated comorbidities, such as sleep fragmentation/loss and obesity. [ABSTRACT FROM AUTHOR]

Despite the high vaccination coverage, potential COVID‐19 vaccine‐induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID‐19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID‐19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (β = −0.27, 95% confidence interval [CI], −0.42, −0.12), and the mean TSH levels were higher by 0.08 mIU/L (β = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID‐19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID‐19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID‐19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels. [ABSTRACT FROM AUTHOR]

Purpose: This paper aimed to assess the incidence of radiotherapy‐induced hypothyroidism (RIHT) in breast cancer patients and correlate it with different factors. Methods: Patients with nonmetastatic breast cancer who received supraclavicular lymph node irradiation as a part of adjuvant radiotherapy from October 2019 to July 2020 were recruited and followed up for 18 months. All patients underwent three‐dimensional conformal radiotherapy and underwent computed tomography simulation. The levels of serum thyroid‐stimulating hormone (TSH), free triiodothyronine and free thyroxine levels were assessed at baseline (before starting radiotherapy) and 9,12, and 18 months after radiotherapy using immunochemilluminescence. Univariate and multivariate analyses were performed to identify significant factors associated with developing hypothyroidism. Results: Twenty patients out of 96 (20.8%) developed hypothyroidism. Baseline TSH (cutoff value >1.42 μIU/ml) was significantly correlated with hypothyroidism. Conclusion: Routine thyroid function tests assessment is recommended for all breast cancer patients at baseline and after radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Guillain‐Barré syndrome (GBS) is generally considered to be monophasic, but some patients have recurrences. The purpose of this study was to clarify the possible link between thyroid parameters and recurrent GBS (RGBS) patients in China. Methods: In this retrospective study we enrolled patients who were admitted to the Department of Neurology of The First Affiliated Hospital of Zhengzhou University from 2014 to 2020 and fulfilled the diagnostic criteria of GBS or Miller Fisher syndrome. We evaluated clinical characteristics; cerebrospinal fluid parameters; and serum levels of thyroid‐stimulating hormone (TSH), free thyroxine, and free triiodothyronine in 320 individuals, including 302 with monophasic GBS and 18 with recurrent GBS. Results: Serum levels of TSH in monophasic GBS patients were significantly lower than those in RGBS patients (P <.001), whereas FT3 levels were higher in the monophasic GBS group (P =.022). Age at onset, incidence of antecedent illness, time from onset to nadir, proportion with acute inflammatory demyelinating polyradiculoneuropathy, and Hughes Functional Grading Scale score at nadir were statistically significant between monophasic GBS patients and RGBS patients (P <.05). The multivariate regression analysis revealed that antecedent illness, AIDP, and high TSH were independent risk factors for RGBS. Our receiver‐operating characteristic curve analysis showed that the risk of recurrence in GBS patients increases when the TSH concentration is higher than 3.87 μIU/mL. Discussion: Our results demonstrate an association between TSH and RGBS. Oxidative stress is one of the possible interpretations for this association. [ABSTRACT FROM AUTHOR]

Hypothyroidism affects up to 5% of the global population. Incidence increases with age and is more common in women and individuals with prolonged estrogen exposure when compared with people who have not been exposed to estrogen. Symptoms can develop slowly and often mimic symptoms of other disorders, including menstrual cycle abnormalities. Understanding risk factors and common presenting symptoms is important in providing high‐quality primary and reproductive care. Diagnosis relies on simple‐to‐obtain, fairly inexpensive testing of thyroid‐stimulating hormone (TSH) levels and confirmation with levels of thyroxine. Management of hypothyroidism usually involves monotherapy with levothyroxine taken on an empty stomach. There are 2 methods for beginning levothyroxine treatment, and outpatient primary care clinicians can use shared decision‐making to determine the best initiation method for each individual. Follow‐up involves regular assessment of levels of TSH and symptom relief. Although some patients may need referral for specialist treatment, the majority of individuals with hypothyroidism can be diagnosed and treated by their outpatient primary care providers. [ABSTRACT FROM AUTHOR]

Maternal thyroid hormones are critical for the growth and development of a healthy fetus. During pregnancy, maternal thyroid hormone production is increased to meet the demands of fetal growth. The purpose of this review is to provide clinicians with current evidence about possible adverse maternal and fetal effects of hypothyroidism in pregnancy, including the role of hypothyroidism in recurrent pregnancy loss. In addition, clinical presentation, evidence‐based screening guidelines, and evidence‐based treatments are discussed. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a common metabolic disorder in the general population, which may arise in hypothyroidism. Apelin is an endogenous ligand that acts as an adiponectin, and is involved in energy storage and metabolism. This study evaluated the effects of apelin administration per se or in combination with T4 on the serum level of thyroid‐stimulating hormone (TSH), body weight, and lipid profile, along with the serum level of apelin, and its mRNA expression in heart, in 6‐propyl‐2‐thiouracil (PTU)‐induced hypothyroid rats. Male Wistar rats were assigned to five different groups: control, H (hypothyroid), H+A, H+T, and H+A+T. All groups except the control one received PTU (0.05%) in the drinking water for 6 weeks. In addition to PTU, the H+A, H+T, and H+A+T groups received apelin (200 μg/kg/day, i.p.), l‐thyroxin (T4) (20 μg/kg/day, via gavage tube), and apelin+T4 during the last 14 days of the trial, respectively. A combined application of T4 and apelin in the H+A+T group effectively diminished mean TSH level, low‐density‐lipoprotein cholesterol/high‐density‐lipoprotein cholesterol ratio, and atherogenic index in these animals when compared with these values for the H group. Coadministration of apelin with T4 may offer valuable therapeutic benefits, specifically lowering blood plasma TSH, lipid disorder, and atherosclerosis biomarkers in PTU‐induced hypothyroid rats. [ABSTRACT FROM AUTHOR]

Objective: Papillary thyroid carcinoma is treated in China mostly with surgery, including total ablation, lobectomy, and lobe and isthmus resection. Therefore, whether thyroid status affects the FNA‐Tg cutoff value in the diagnosis of cervical lymph node metastasis deserves our attention. In addition, we investigated the influence of serum Tg, TSH, and TgAb on the accuracy of using FNA‐Tg for diagnosis. Methods: Our retrospective analysis included 189 suspected cervical lymph nodes, and we determined whether the cutoff value of FNA‐Tg was affected by thyroid status, sTg, sTSH, and sTgAb. Results: In thyroid present cases, the optimal cutoff value of FNA‐Tg was 2.3 ng/ml (sensitivity 96.2%, specificity 100%), and in the thyroid absent cases, the optimal cutoff value of FNA‐Tg was 0.7 ng/ml (sensitivity 97.6%, specificity 96.0%). Although serum Tg, TSH, and TgAb were weakly correlated with FNA‐Tg values, they did not affect the diagnostic performance of the optimal cutoff value of FNA‐Tg according to thyroid status. Conclusions: The optimal cutoff value of FNA‐Tg should be selected according to the thyroid status (2.3 ng/ml for thyroid present cases and 0.7 ng/ml for thyroid absent cases) to ensure the efficient diagnosis of cervical metastatic lymph nodes of papillary thyroid carcinoma. It was determined that sTg, sTSH, and sTg‐Ab cannot influence the diagnostic performance of FNA‐Tg. The combination method of FNA‐Tg and FNAC is the most optimal choice for the diagnosis of lymph nodes metastasis. [ABSTRACT FROM AUTHOR]

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population‐based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid‐stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio‐economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine‐deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries. [ABSTRACT FROM AUTHOR]

Objective: In this study, we investigated the effect of thyroid‐stimulating hormone (TSH) level on the outcomes of in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Data pertaining to 60 patients who underwent IVF between May 2017 and May 2018 were included in the study. Thirty‐two patients were diagnosed as PCOS (PCOS group) and 28 patients had tubal infertility (control group). Serum and follicular fluid TSH levels and follicular cyclic AMP (cAMP) level were detected by ELISA. TSH receptor (TSHR) expression level in granulosa cells was quantified by RT‐PCR and Western blot. Results: In the PCOS group, oocyte maturation rate and fertilization rate were significantly lower than in the control group. Serum and follicular fluid TSH levels and ovarian cAMP level were higher in the PCOS group with an upregulation of ovarian TSHR. On multivariate linear regression analysis, fertilization rate showed a negative correlation with TSH levels in serum (B = −0.106, P = 0.005) and follicular fluid (B = −0.107, P = 0.001). Conclusion: In PCOS patients, TSH levels, both in serum and follicular fluid, were negatively correlated with IVF oocyte maturation rate and fertilization rate. The effect of TSH on controlled ovarian hyperstimulated oocyte growth was likely mediated by the TSHR/cAMP signaling pathway. Synopsis: Thyroid‐stimulating hormone levels in serum and follicular fluid are negatively correlated with both oocyte maturation rate and fertilization rate during IVF. [ABSTRACT FROM AUTHOR]

Background: Radioiodine (131I) is the treatment of choice for hyperthyroidism in cats, but current 131I‐dosing protocols can induce iatrogenic hypothyroidism and expose azotemia. Objectives: To develop a cat‐specific algorithm to calculate the lowest 131I dose to resolve hyperthyroidism, while minimizing risk of iatrogenic hypothyroidism and subsequent azotemia. Animals: One thousand and four hundred hyperthyroid cats treated with 131I. Methods: Prospective case series (before‐and‐after study). All cats had serum concentrations of thyroxine (T4), triiodothyronine (T3), and thyroid‐stimulating hormone (TSH) measured (off methimazole ≥1 week). Using thyroid scintigraphy, each cat's thyroid volume and percent uptake of 99mTc‐pertechnatate (TcTU) were determined. An initial 131I dose was calculated by averaging dose scores for T4/T3 concentrations, thyroid volume, and TcTU; 80% of that composite dose was administered. Twenty‐four hours later, percent 131I uptake was measured, and additional 131I administered, as needed, to deliver an adequate radiation dose to the thyroid tumor(s). Serum concentrations of T4, TSH, and creatinine were determined 6 to 12 months later. Results: The median calculated 131I dose was 1.9 mCi (range, 1.0‐10.6 mCi); 1380 cats required additional 131I administration on day 2. Of the cats, 1047 (74.8%) became euthyroid, 57 (4.1%) became overtly hypothyroid, 240 (17.1%) became subclinically hypothyroid, and 56 (4%) remained hyperthyroid. More overtly (71.9%) and subclinically (39.6%) hypothyroid cats developed azotemia than euthyroid cats (14.2%; P <.0001). Conclusions and Clinical Importance: Our algorithm for calculating individual 131I doses resulted in cure rates similar to historical treatment rates, despite much lower 131I doses. This algorithm appears to lower prevalence of both 131I‐induced overt hypothyroidism and azotemia. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported that the thyroid‐stimulating hormone (TSH) reference interval is susceptible to external factors, such as age, sex, race, region and iodine intake. However, no meta‐analysis has comprehensively explored the effect of these factors on the TSH reference interval. Methods: Articles published from January 1960 to January 2020 were searched in PubMed, Embase, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 19 studies were ultimately included. All data were analysed using Review Manager 5.3, STATA 16.0 software, GraphPad Prism 8.0 and Microsoft Excel 2010 to draw the TSH concentration curve. Results: The TSH reference interval was significantly influenced by sex and age. The mean of TSH concentration in females was 0.27 mIU/L higher than that in males. Reference interval of TSH is divided into 20–59 years old and >60 years old age groups in males, and 20–39 years old and >40 years old age groups in females. Regardless of sex, TSH concentrations all increase with age. In iodine‐deficient areas, TSH reference intervals were generally lower than those in iodine‐sufficient or iodine‐excessive areas. The TSH reference interval in Asia and North American countries was generally higher than that in most European countries. In the subgroup analyses of sample size, region and assay methods and manufacturers, the between‐group differences were significant. Conclusion: The TSH reference interval was significantly influenced by sex, age, iodine intake, sample size, region, and assay methods and manufacturers, but other factors should not be ignored. Therefore, it is necessary for each laboratory to validate an appropriate TSH reference interval based on local conditions. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG. Material and methods: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4. Results: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47‐3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36‐3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty‐one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03). Conclusions: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to prospectively evaluate whether TSH levels at baseline were associated with incident depression after four years of follow‐up in a cohort of middle‐aged adults, the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil). Methods: TSH and free‐thyroxine (FT4) levels were evaluated at baseline. Depression diagnoses were performed using the Clinical Interview Schedule—Revised (CIS‐R) at baseline and after a 4‐year follow‐up. Poisson regression models (95% Confidence Intervals) were built to evaluate the association between TSH quintiles at baseline and incident depression. All analyses were stratified by sex. Models were presented crude, adjusted for age and sex; and further adjusted for race, education, BMI, smoking, alcohol consumption, use of antidepressants/benzodiazepines, kidney function and comorbidities. Results: Mean age was 51.5 years, and 51.2% were women. Overall, low TSH levels (1st quintile) were associated with incident depression (adjusted RR = 1.36, 95% CI 1.02–1.81), remaining significant for women (adjusted RR = 1.64, 95% CI 1.15–2.33), but not for men. The same results were found when restricting analysis to euthyroid participants (adjusted RR = 1.46, 95% CI 1.08–1.99), also significant for women only (adjusted RR = 1.63, 95% CI 1.12–2.38). Conclusions: Our results showed that low TSH levels were positively associated with incident depression, particularly among women. Similar results were found when restricting the analysis to euthyroid participants. In contrast, high TSH levels were inversely associated with incident depression, also among women. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the extent of thyroid function control among pregnant women who had previously undergone a therapeutic thyroidectomy. Design: Retrospective cohort study. Setting: The largest health maintenance organization in Israel. Participants: All female patients who were pregnant between May, 2001 and September, 2012 and had a medical history of thyroid surgery. Main outcome measure: The thyroid‐stimulating hormone (TSH) levels throughout the pregnancy were compared to recommended trimestral values. A multivariate analysis was performed to determine risk factors for not attaining TSH recommended range. Results: A total of 477 females with a history of thyroid surgery had given 701 births during the study period. Forty‐three percent (n = 203), had thyroidal malignancy. Nearly half of the women underwent total thyroidectomy (43.4%, n = 207). The women's TSH values were within the recommended range in only 60% (n = 350) of the pregnancies during the first trimester (0.1‐2.5 mIU/L), in 61% (n = 335) during the second trimester (0.2‐3 mIU/L), and in 70% (n = 338) during the third trimester (0.3‐3 mIU/L). In multivariate analysis, women that underwent a total thyroidectomy due to a benign thyroid disease, were at the highest risk for not attaining target TSH levels. Conclusions: This very large cohort of pregnant women with a past history of thyroid surgery demonstrated a significant percentage of pregnancies with TSH values above the recommended range. Women that underwent a total thyroidectomy due to benign thyroid disease were at the highest risk for gestational hypothyroidism. [ABSTRACT FROM AUTHOR]

Middle‐aged and elderly women are at a higher risk of subclinical hypothyroidism (SHypo). Menopause is an important period of metabolic change in women and thyroid hormones are closely related to metabolic status. Neck circumference (NC) is a simple anthropometric index that reflects upper body fat accumulation. Therefore, this study aimed to explore the relationship between NC and thyroid hormones in postmenopausal women. A total of 1050 postmenopausal women were enrolled from Shanghai Zhabei communities (888 euthyroid subjects and 162 SHypo patients). Anthropometric parameters, including NC, were measured. The measurements of serum thyroid hormones were performed by electrochemical luminescence immunoassay. The results showed NC was positively correlated with thyroid‐stimulating hormone (TSH) (r =.064, P =.039). TSH and the proportion of SHypo patients increased significantly in those with elevated NC (both P <.05). In logistic regression analysis, the risk of SHypo increased by 46.4% in those with elevated NC (OR = 1.464 [1.035–2.071], P =.031). After adjusting for metabolic confounding factors, the positive association disappeared (P =.112). Multiple linear regression analysis showed there were no significant correlations between NC and TSH in either univariate or multivariate model in the total population (both P >.05). And in the subgroup analysis of euthyroid and SHypo individuals, NC was also not related to TSH (all P >.05). In conclusion, there was no independent association between NC, a simple anthropometric index for upper body fat accumulation, and serum TSH levels in Chinese euthyroid and SHypo postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: For the biochemical follow‐up of benign thyroid nodules, some authors recommend periodic lifelong measurement of thyroid‐stimulating hormone (TSH) to assess for the development of toxic nodules over time. The purpose of this retrospective study was to assess the incidence of thyroid dysfunction over time in patients with benign thyroid nodule(s), with a normal TSH at diagnosis and to identify any factors that may predict biochemical dysfunction over time. Methods: Medical records of patients with the diagnosis of thyroid nodule(s) between January 2011 and August 2014 were reviewed. Patients who had TSH measurement within 1 year of initial diagnostic ultrasound (US) were included. Results: One‐hundred fifty‐seven patients identified with thyroid nodule(s) satisfied inclusion criteria. At a median follow‐up of 45 (34‐63) months, 13 (8.3%) patients developed thyroid dysfunction. The mean initial TSH in the group which developed subclinical hyperthyroidism (0.65 mIU/mL) was statistically different from the group that did not develop thyroid dysfunction (1.37 mIU/mL, P: 0.007). More patients with TSH <1 mIU/L developed thyroid dysfunction as compared to subjects with TSH ≥1 mIU/L (P:.022). There was no significant difference in the incidence of thyroid dysfunction on the basis of gender, race, smoking status, TPO Ab positivity and number of nodules at diagnosis. Conclusions: We recommend re‐examining the current practice and clinical utility of frequent TSH monitoring in all patients with thyroid nodules, particularly if initial TSH level is ≥1 mIU/L. [ABSTRACT FROM AUTHOR]

Metal nanoparticle surfaces are used for peroxidase‐ and oxidase‐like nanozymes but not for esterase‐like nanozymes. It is challenging to obtain rapid catalytic hydrolysis on a metal surface and even more so without a catalytically labile substrate. Here, we report that metal nanoparticle surfaces rapidly catalyze non‐redox ester hydrolysis in the presence of redox H3N−BH3 (AB). Metal hydrides are readily generated on a Pt nanoparticle (PtNP) from AB, and as a result the PtNP becomes electron‐rich, which might assist nucleophilic attack of H2O on the carbonyl group of an ester. The nanozyme system based on PtNP, AB, and 4‐aminonaphthalene‐1‐yl acetate provides an electrochemical signal‐to‐background ratio much higher than natural enzymes, due to the rapid ester hydrolysis and redox cycling involving the hydrolysis product. The nanozyme system is applied in a sensitive electrochemical immunosensor for thyroid‐stimulating hormone detection. The calculated detection limit is approximately 0.3 pg mL−1, which indicates the high sensitivity of the immunosensor using the PtNP nanozyme. [ABSTRACT FROM AUTHOR]

Background: In cats, nonthyroidal illness affects serum thyroid hormone concentrations. Serum thyroxine (T4) and triiodothyronine (T3) concentrations commonly decrease, whereas free T4 (fT4) concentrations vary unpredictably. Limited information exists regarding effects on serum thyrotropin (thyroid‐stimulating hormone [TSH]) concentrations in cats with nonthyroidal illness syndrome (NTIS). Objectives: To characterize alterations in thyroid function that develop in cats with NTIS and to correlate these alterations with severity and outcome of the nonthyroidal illness. Animals Two hundred and twenty‐two cats with NTIS and 380 clinically normal cats of similar age and sex. Methods: Prospective, cross‐sectional study. All cats had serum T4, T3, free T4, and TSH concentrations measured. Cats were grouped based on illness severity and 30‐day survival. Results: Cats with NTIS had lower serum T4 and T3 concentrations than did normal cats (P <.001). Serum fT4 and TSH concentrations did not differ between groups. Serum T4, T3, and fT4 concentrations progressively decreased with increasing disease severity (P <.001). The 56 cats that died had lower T4, T3, and TSH concentrations than did the 166 survivors, with no difference in fT4 concentration. Multivariable logistic regression modeling indicated that serum T4 and TSH concentrations both predicted survival (P <.02). Conclusions and Clinical Importance: Cats with NTIS commonly develop low serum T4, T3, and TSH concentrations, the prevalence and extent of which increases with disease severity. Clinicians should consider evaluating thyroid function in cats with severe NTIS, because doing so could help determine probability of successful treatment responses before investing considerable time, effort, and finances in addressing the underlying disease. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the response to the thyrotropin‐releasing hormone (TRH) stimulation test in very low‐birth weight (VLBW) infants to elucidate the aetiology of transient hypothyroxinaemia of prematurity (THOP). Design and Methods: We performed TRH stimulation tests on 43 VLBW infants. Subjects were divided into two groups; a THOP group (N = 11; basal TSH < 15 mU/L and basal FT4 ≤ 0.8 ng/dL) and a non‐THOP group (N = 32; basal TSH < 15 mU/L and basal FT4 > 0.8 ng/dL). Basal FT4 and FT3 were measured before, and TSH (0, 30, 60, 90, 120 and 180 minutes) was measured after, the administration of TRH (7 µg/kg). We calculated the ratio of TSH 180 minutes to THS 0 minute as the primary outcome. We also collected data on T3 and rT3 in this study. Results: In both groups, TSH 30 minutes values were the highest. However, the ratios of TSH 180 minutes to THS 0 minutes in the non‐THOP group and the THOP group were (median [IQR]) 1.3 [1.0‐1.7] and 3.0 [1.5‐5.3] (P <.01). No significant differences were observed in T3 (1.0 [0.8‐1.3] and 0.7 [0.4‐0.7] ng/mL, P =.06). However, in the THOP group, rT3 was significantly lower than that of the non‐THOP group (168.0 [148.1‐197.0] and 92.9 [74.7‐101.6] pg/mL, P <.01). Conclusions: The delayed decrease in the TSH concentration after the peak for the TRH tests and decreased levels of rT3 suggest that the main aetiology for THOP is suppression at the level of the hypothalamus, but not inactivation of peripheral thyroid hormone metabolism. [ABSTRACT FROM AUTHOR]

Whether thyroid dysfunction plays a causal role in the development of cancer remains inconclusive. We conducted a two‐sample Mendelian randomization study to investigate the associations between genetic predisposition to thyroid dysfunction and 22 site‐specific cancers. Single‐nucleotide polymorphisms associated with four traits of thyroid function were selected from a genome‐wide association meta‐analysis with up to 72,167 European‐descent individuals. Summary‐level data for breast cancer and 21 other cancers were extracted from the Breast Cancer Association Consortium (122,977 breast cancer cases and 105,974 controls) and UK Biobank (367,643 individuals). For breast cancer, a meta‐analysis was performed using data from both sources. Genetically predicted thyroid dysfunction was associated with breast cancer, with similar patterns of associations in the Breast Cancer Association Consortium and UK Biobank. The combined odds ratios of breast cancer were 0.94 (0.91–0.98; p = 0.007) per genetically predicted one standard deviation increase in TSH levels, 0.96 (0.91–1.00; p = 0.053) for genetic predisposition to hypothyroidism, 1.04 (1.01–1.07; p = 0.005) for genetic predisposition to hyperthyroidism and 1.07 (1.02–1.12; p = 0.003) per genetically predicted one standard deviation increase in free thyroxine levels. Genetically predicted TSH levels and hypothyroidism were inversely with thyroid cancer; the odds ratios were 0.47 (0.30–0.73; p = 0.001) and 0.70 (0.51–0.98; p = 0.038), respectively. Our study provides evidence of a causal association between thyroid dysfunction and breast cancer (mainly ER‐positive tumors) risk. The role of TSH and hypothyroidism for thyroid cancer and the associations between thyroid dysfunction and other cancers need further exploration. What's new? Whether thyroid dysfunction plays a causal role in the development of cancer remains inconclusive. This two‐sample Mendelian randomization study investigated the associations between genetic predisposition to thyroid dysfunction and 22 site‐specific cancers. Evidence of a causal inverse association was found between thyroid‐stimulating hormone levels and overall cancer. Increased thyroid‐stimulating hormone levels and hypothyroidism were associated with decreased risk of thyroid and breast (mainly ER‐positive) cancer, whereas hyperthyroidism and increased free thyroxine levels were associated with a higher risk of breast (mainly ER‐positive) cancer. The results suggest that treatment of subclinical and diagnosed hyperthyroidism may be an efficient cancer prevention strategy. [ABSTRACT FROM AUTHOR]

In contrast to most rhodopsin‐like G protein‐coupled receptors, the glycoprotein hormone receptors (GPHR) have a large extracellular N‐terminus for hormone binding. The hormones do not directly activate the transmembrane domain but mediate their action via a, thus, far only partially known Tethered Agonistic LIgand (TALI). The existence of such an intramolecular agonist was initially indicated by site‐directed mutation studies and activating peptides derived from the extracellular hinge region. It is still unknown precisely how TALI is involved in intramolecular signal transmission. We combined systematic mutagenesis studies at the luteinizing hormone receptor and the thyroid‐stimulating hormone receptor (TSHR), stimulation with a drug‐like agonist (E2) of the TSHR, and structural homology modeling to unravel the functional and structural properties defining the TALI region. Here, we report that TALI (a) is predisposed to constitutively activate GPHR, (b) can by itself rearrange GPHR into a fully active conformation, (c) stabilizes active GPHR conformation, and (d) is not involved in activation of the TSHR by E2. In the active state conformation, TALI forms specific interactions between the N‐terminus and the transmembrane domain. We show that stabilization of an active state is dependent on TALI, including activation by hormones and constitutively activating mutations. [ABSTRACT FROM AUTHOR]

Background: There is no clear cutoff value for thyroid‐stimulating hormone (TSH) level that defines subclinical hypothyroidism (SCH). Moreover, TSH levels can be affected by numerous factors. Although mild SCH has been implicated in miscarriage, the relationship between TSH levels and miscarriage remains unelucidated. Methods: We reviewed nine known risk factors affecting TSH levels and 28 studies investigating the potential association between mild SCH and miscarriage, examining whether these factors were considered. Main findings: Among 28 studies that examined whether mild SCH (TSH > 2.5 mIU/L) contributed to miscarriage, thyroid antibodies were measured in only 15. TSH measurement methods were described in 18 studies. Although the iodinated contrast medium used in hysterosalpingography (HSG) is stored in the body for a long time and is a risk factor for mild SCH, only one study described its potential impact on TSH levels. Nine studies, which concluded that mild SCH contributed to miscarriage, had thyroid status evaluated only after the onset of pregnancy, but not before. Conclusion: TSH levels can be significantly affected by patient demographics and health history, country of origin, and fertility treatment. It is important to consider these factors while evaluating mild SCH. It remains unclear how mild SCH contributes to miscarriage. [ABSTRACT FROM AUTHOR]

Background and Aim: Hypothyroidism might play a crucial role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The association of subclinical hypothyroidism with NAFLD has been inconsistent. The relationship of NAFLD with thyroid function parameters and subclinical hypothyroidism was determined. Methods: This cross‐sectional study included 70 patients with subclinical hypothyroidism and 70 controls with euthyroidism matched according to gender, age, and body mass index (BMI). NAFLD was diagnosed via abdominal ultrasonography. The association between NAFLD and subclinical hypothyroidism was analyzed. Results: The prevalence of NAFLD was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Multivariate analysis showed that subclinical hypothyroidism was an independent risk factor of NAFLD adjusted by metabolic‐related factors, such as BMI, triglyceride, high‐density lipoprotein‐cholesterol, hypertension, and diabetes. Thyroid‐stimulating hormone (TSH) was an independent risk factor of NAFLD adjusted by the same metabolic‐related factors, but free thyroxine (FT4) was not a risk factor. The FIB‐4 index, a noninvasive marker of liver fibrosis was significantly higher in patients with subclinical hypothyroidism than in those with euthyroidism. Compared with patients with euthyroidism, the proportion of the FIB‐4 index ≥2.67 was significantly higher, and the proportion of the FIB‐4 index <1.30 was lower in patients with subclinical hypothyroidism. Conclusions: TSH elevation even within the euthyroid range is an independent risk factor of NAFLD and may influence the progression of liver fibrosis, even with a normal FT4 level. [ABSTRACT FROM AUTHOR]

Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population‐based, case–control study among a sample of children born during 2000–2003 in Southern California. We examined neonatal thyroid‐stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early‐onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln‐transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj‐OR: 1.00, 95% CI: 0.79–1.26) nor ID (adj‐OR = 1.01, 95% CI: 0.73–1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj‐OR: 0.50, 95% CI: 0.26–0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444–455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc. Lay Summary: Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research. [ABSTRACT FROM AUTHOR]

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid‐stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C‐reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = −0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis. [ABSTRACT FROM AUTHOR]

Purpose: To study the effects of mildly elevated thyroid‐stimulating hormone (TSH) levels and thyroid antibodies on pregnancy rates among infertile women and their potential contribution to prolonged infertility treatment. Methods: This case‐control study included 1479 women who underwent infertility treatment between March 2015 and August 2017. Cumulative pregnancy and miscarriage rates after assisted reproductive technology (ART) or non‐ART treatments were compared between women with TSH <2.5 mIU/L and those with TSH 2.5‐3.5 mIU/L and between women with and without thyroid antibody positivity. Results: The cumulative pregnancy rate of women with TSH 2.5‐3.5 mIU/L was similar to that of women with TSH <2.5 mIU/L in the non‐ART (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.56‐1.23) and ART (HR, 1.17; 95% CI, 0.93‐1.47) groups. Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) had no correlation with cumulative pregnancy rates. In the non‐ART and ART groups, HRs for TgAb were 0.87 (95% CI, 0.55‐1.32) and 1.09 (95% CI, 0.84‐1.39) and HRs for TPOAb were 0.88 (95% CI, 0.52‐1.39) and 1.29 (95% CI, 0.97‐1.68), respectively. Conclusions: Cumulative pregnancy rates and miscarriage rates were similar between women with TSH <2.5 mIU/L and those with TSH 2.5‐3.5 mIU/L and were independent of thyroid antibody positivity. [ABSTRACT FROM AUTHOR]

Background: This study was to investigate the association of fasting serum glucose (FSG), thyroid‐stimulating hormone (TSH), and thyroid hormones with papillary thyroid cancer (PTC). Methods: A total of 649 participants were included in this case‐control study. The associations of FSG, TSH, free triiodothyronine (FT3) and free thyroxine (FT4) with PTC were estimated using an unconditional logistic regression. Results: Compared with the lowest quintile of TSH levels, odds ratios (ORs) and 95% confidence intervals (CIs) for association between PTC risk and highest quintile of TSH levels were 1.67 (95% CI, 0.99‐2.83). However, this risk correlation was more significant in PTC cases with ≤1.0 cm tumor size (adjusted OR, 1.95; 95% CI, 1.08‐3.54; adjusted P‐trend, 0.05). The PTC risk was also inversely associated with the serum FT3 level in all participants (adjusted P‐trend, 0.001), but positively associated with the serum FT4 (adjusted P‐trend, 0.001) and FSG (adjusted P‐trend, 0.01) levels. Among the participants without diabetes, the individuals with high FSG levels and abnormal TSH concentration had an increased PTC risk (adjusted OR, 3.38; 95% CI, 1.78‐6.42). Conclusion: The current study provides evidence for the association of FSG, TSH, and thyroid hormones (FT3 and FT4) with PTC risk. However, larger relative studies are needed. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationship of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels with hypertension subtypes. 1056 euthyroid adults were included as research samples. They underwent measurement of clinic blood pressure and 24-hours ambulatory blood pressure monitoring. Then, they were divided into normotension (NT), white coat hypertension (WCH), masked hypertension (MHT), and sustained hypertension (SHT) groups. The 24-hours dynamic electrocardiogram was performed to analyze the heart rate variability (HRV), so as to reflect the cardiac autonomic function. The relationship between hypertension subtypes, thyroid function, and HRV was analyzed. The TSH concentration was significantly higher in the SHT group than in the NT group (P = 0.001). The FT3 concentration was higher in the SHT group than in the NT and MHT groups (P = 0.013, P = 0.008), while the FT4 concentration was significantly higher in the WCH group than in the NT group (P = 0.002). The changes in HRV were observed between the SHT, WCH, and MHT groups and the NT groups, as well as between the SHT and the MHT groups. The multiple linear regression analysis also showed that FT3, HRV (RMSSD and PNN50), and blood pressure levels linearly correlated with one another (P < 0.05). Meanwhile, the linear regression analysis showed a linear negative correlation between FT4 and HRV (SDANN) in the WCH + NT group (P = 0.001). Thyroid function was closely related to hypertension subtypes such as WCH probably due to the changes in the cardiac autonomic function. [ABSTRACT FROM AUTHOR]

Introduction: Iodine is essential for thyroid function, and iodine deficiency during pregnancy is common in Europe and the USA. However, no published studies have examined the role of iodine deficiency in the relation between thyroid function and gestational diabetes mellitus (GDM).Material and Methods: We conducted a population-based, nested case-control study within the Finnish Maternity Cohort using pregnancy and perinatal outcome data from the Finnish Maternal Birth Register. We randomly selected 224 GDM cases with singleton pregnancies and 224 controls without GDM from all singleton births occurring in Finland during 2012-2013. Blood was drawn at 10-14 weeks' gestation and analyzed for serum iodide, thyroglobulin, and thyroid-stimulating hormone (TSH) concentrations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of GDM.Results: Very high thyroglobulin concentration (>95% percentile; >83 μg/L) was not associated with significantly altered odds of GDM compared to those with normal levels (OR 0.41; 95% CI: 0.12, 1.38). High concentrations of TSH were also not associated with increased odds of GDM compared to normal levels of TSH (OR 0.45; 95% CI: 0.06, 3.18). Women in the lowest 5th percentile (<1.58 ng/mL) of iodine did not have increased odds of GDM compared to those with iodide in the highest quartile (OR 0.39; 95% CI: 0.11, 1.35).Conclusions: Low levels of iodide and thyroid function in early pregnancy are not associated with increased risk of GDM in this mildly iodine-deficient population. [ABSTRACT FROM AUTHOR]

Objective: The re‐emergence of iodine deficiency in the UK has recently been reported in a large cohort of teenage girls including from Northern Ireland (NI) using the gold standard spot urinary iodine concentration. We wished to explore and confirm this by analysing neonatal thyroid‐stimulating hormone (nTSH) levels in the NI population. Design: We analysed the nTSH heel prick tests results from the NI national screening database between 2003 and 2014. The WHO proposes a definition for population iodine sufficiency at <3% of the population with nTSH results >5 mIU/L. Methods: Anonymized results from 288 491 nTSH tests were retrieved, and prevalence rates of results at increasing cut‐offs including >2 mIU/L and >5 mIU/L calculated. We also assessed for possible seasonal variation in nTSH results. Results: An overall population prevalence of 0.49% with TSH >5 mIU/L was found, indicating population iodine sufficiency with no year attaining a prevalence >3%. The prevalence of nTSH >2 mIU/L decreased to 4.1% in 2007 and subsequently increased to 9.8% in 2014. Modest seasonal variation was also detected, with higher levels among April/May births. Conclusions: The neonatal TSH database suggests iodine sufficiency in the NI population. However, the rising frequency of results >2 mIU/L may indicate an emerging mild iodine deficiency. This is one of the largest and longest studies of its kind in the UK and the first carried out in NI. The summer months may be a time of increased risk of iodine deficiency in our pregnant women whose requirements are increased and who are not currently targeted by any iodine fortification programme in the UK. [ABSTRACT FROM AUTHOR]

Thyroid hormones (THs) have profound effects on cardiovascular functions, suggesting that THs may contribute to the development of elevated blood pressure (BP). Few studies, however, have systematically assessed the relationship between THs and elevated BP. We therefore conducted a cross-sectional study to examine how serum THs concentrations are related to the prevalence of elevated BP in a euthyroid population. This study (n = 12 487) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay. Elevated BP was defined according to the JNC 8 criteria. Analysis of covariance and multiple logistic regression models were used to assess the relationships between FT3, FT4, and TSH quartiles and elevated BP. The multivariable-adjusted odds ratios (95% confidence interval) of elevated BP for gradual increase in the FT3, FT4, and TSH quartiles, when compared to the lowest quartiles were 1.08 (0.97, 1.21), 1.24 (1.12, 1.39), and 1.32 (1.18, 1.47); 1.18 (1.06, 1.32), 1.18 (1.06, 1.31), and 1.24 (1.11, 1.38); 1.06 (0.96, 1.19), 1.06 (0.95, 1.18), and 1.03 (0.93, 1.15), respectively. Our study demonstrated that FT3 and FT4 are positively related to the prevalence of elevated BP in euthyroid adults, but no significant relationship was found between TSH and elevated BP. [ABSTRACT FROM AUTHOR]

Abstract: Aim: A sustained proportion of advanced hepatocellular carcinoma (HCC) patients worldwide received either chemotherapy or sorafenib. However, to date, effective and convenient biomarkers to predict their therapeutic outcomes remained elusive. Hypothyroidism was associated with favorable anticancer treatment outcomes in several advanced cancers. Here, we aimed to investigate the potential of using thyroid‐stimulating hormone (TSH) and free T4 (FT4) levels as biomarkers to predict clinical outcomes in HCC patients receiving chemotherapy or sorafenib. Methods: Total 123 advanced HCC patients at Barcelona Clinical Liver Cancer Stage C were included. They were separated into two cohorts, one treated by sorafenib (n = 62) and the other by chemotherapy (n = 61). Clinical data including TSH and FT4 were retrieved and correlated with treatment outcomes. Results: Because of restriction in local insurance policy, the baseline liver function reserve was better in patients receiving sorafenib. Therefore, the two cohorts were analyzed separately. The results showed that a higher (> median) TSH × FT4 value was independently associated with favorable time‐to‐tumor progression (P = 0.006) and overall survival (P = 0.002) if chemotherapy was provided; whereas it was associated with unfavorable time‐to‐tumor progression (P = 0.017) and overall survival (P = 0.001) if sorafenib was administrated. These opposite associations remained valid when patients with Child–Pugh class A liver function from either cohort were included for analysis. Conclusion: A novel thyroid function index, TSH × FT4, significantly predicted opposite clinical outcomes in advanced HCC patients receiving sorafenib or chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate predictors of low thyroid‐stimulating hormone (TSH) persisting beyond the first trimester and associated pregnancy outcomes. Methods: We retrospectively assessed the association between low first‐trimester TSH and obstetric outcomes of singleton pregnancies in southern Israel between 2001 and 2011. We included women with first‐trimester TSH and at least one other THS measurement. Clinical data were from maternity and community medical records. Results: Among 3761 women, 185 (4.9%) had a TSH of 0.10 mIU/L or less in the first trimester. Multiple of the median human chorionic gonadotropin was higher in women with TSH of 0.40 mIU/L or less versus 0.41–4.0 mIU/L, but was not associated with higher rates of persistent low TSH. Maternal age (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00–1.16; per yearly increment), free thyroxine (FT4; OR 1.11, 95% CI 1.03–1.20; per ng/dL increment), and TSH of 0.10 mIU/L or less (OR 3.06, 95% CI 1.38–6.80 vs 0.21–0.40 mIU/L) were independent predictors of persistent low TSH. No adverse pregnancy outcomes occurred in women with low first‐trimester TSH. Conclusions: Low TSH persisting beyond the first trimester was more common with increasing maternal age, elevated FT4, and TSH below 0.10 mIU/L, but was not associated with obstetric complications. [ABSTRACT FROM AUTHOR]

Summary: Uncorrected thyroid dysfunction in pregnancy has well‐recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre‐empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves’ disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. [ABSTRACT FROM AUTHOR]

Aim: Subclinical hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) levels with the normal concentrations of thyroxine (T4) or free thyroxine (fT4), and its clinical significance is unclear. The purpose of this study is to investigate the prevalence of subclinical hypothyroidism in children and adolescents and determine the relationship between lipid profiles, insulin resistance and thyroid hormones.Methods: A retrospective, cross-sectional study was performed using data from a subset of the KNHANES VI. The subjects whose ages were in the range of 10-19 years were enrolled when their thyroid function tests were available (n = 1104), and their laboratory and anthropometric data were analysed.Results: Subclinical hypothyroidism was more commonly identified in the obese group (27 of 111) compared to the other groups (127 of 993) (24.3 vs. 12.8%, P = 0.002). Total cholesterol and triglyceride levels were higher in a group with subclinical hypothyroidism. Body mass index (BMI) was positively correlated with serum concentrations of the TSH and negatively correlated with serum concentrations of fT4 after adjusting for age. The concentrations of total cholesterol and triglyceride were positively correlated with the TSH concentrations following adjustment for age and BMI standard deviation scores. The fT4 concentrations were negatively linked with total cholesterol after adjusting for age and BMI standard deviation scores. No significant correlation was found between insulin resistance index and TSH and fT4.Conclusions: Subclinical hypothyroidism was common in the obese group, and the concentrations of TSH were linked with the lipid profile. Subclinical hypothyroidism in obese children or adolescents should be closely monitored while also evaluating metabolic risk factors. [ABSTRACT FROM AUTHOR]

Summary: Objective: Thyroid hormones (THs) are primarily responsible for the regulation of energy homeostasis and metabolism. However, few prospective studies have assessed the association between THs and metabolic syndrome (MetS) in a general population. We therefore designed a cohort study to examine whether serum TH levels within the reference range are predictive factors for developing MetS in adults. Design: Prospective cohort study. Participants: A prospective study (n = 6119) was performed in Tianjin, China. Participants without a history of MetS were followed up for 1 to 3 years with a median follow‐up duration of 2 years. Measurements: Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid‐stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay. MetS was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. THs, TSH levels and MetS were assessed yearly during the follow‐up. Adjusted Cox proportional hazards regression models were used to assess the associations between FT3, FT4 and TSH quintiles and MetS. Results: The incidence of MetS was 17.7% (96 per 1000 person‐years). In the final multivariate models, the hazard ratios (95% confidence interval) for MetS across serum FT3 quintiles were 1.00 (reference), 1.03 (0.84, 1.25), 1.14 (0.94, 1.38), 1.09 (0.90, 1.32) and 1.33 (1.11, 1.61), respectively (P for trend <.01). However, no significant associations between FT4, TSH and MetS were observed. Conclusions: This population‐based prospective cohort study suggests that increased serum FT3 level, rather than FT4 and TSH, is an independent predictor for developing MetS in euthyroid subjects. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism. [ABSTRACT FROM AUTHOR]

Background: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. Objectives: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. Animals: Two hundred and sixty‐two hyperthyroid cats and 206 aged‐matched, clinically normal cats. Methods: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4, and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131I) and classified 131I‐treated cats as azotemic or nonazotemic based on persistent, post‐treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. Results: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4–8 months (median, 6 months) after 131I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre‐azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. Conclusions and Clinical Importance: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false‐positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats). [ABSTRACT FROM AUTHOR]

Background Previous data on the association of thyroid function with total mortality, cardiovascular disease ( CVD) outcomes and sudden cardiac death ( SCD) are conflicting or limited. We investigated associations of thyroid-stimulating hormone ( TSH) with these outcomes in a nationwide population-based prospective cohort study. Methods We examined 5211 participants representative of the Finnish population aged ≥30 years in 2000-2001 and followed them for a median of 13.2 years. Using Cox proportional hazards regression models adjusted for baseline age, gender, smoking, diabetes, systolic blood pressure and total and high-density lipoprotein cholesterol, we assessed the associations of continuous baseline TSH and TSH categories (low [<0.4 mU/L], reference range [0.4-3.4 mU/L] and high [>3.4 mU/L]) with incident total mortality, SCD, coronary heart disease events, stroke, CVD, major adverse cardiac events and atrial fibrillation. Results High TSH at baseline was related to a greater risk of total mortality ( HR 1.34, 95% CI 1.02-1.76) and SCD ( HR 2.28, 95% CI 1.13-4.60) compared with TSH within the reference range. High TSH was not associated with the other outcomes ( P ≥ .51), whereas low TSH was not associated with any of the outcomes ( P ≥ .09). TSH at baseline over the full range did not have a linear relation with any of the outcomes ( P ≥ .17). TSH showed a U-shaped association with total mortality after a restricted cubic spline transformation ( P = .01). Conclusions Thyroid function abnormalities could be linked with higher risks of total mortality and SCD. Large-scale randomized studies are needed for evidence-based recommendations regarding treatment of mild thyroid failure. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The exact mechanism of arterial stiffness in fibromyalgia (FM) remains unclear. The present study aimed to evaluate the association between thyroid function and markers of arterial function in postmenopausal FM patients. Methods: This study included 163 postmenopausal FM patients without any known cardiovascular diseases and within a normal reference range of thyroid‐stimulating hormone (TSH) level. Clinical parameters including the Fibromyalgia Impact Questionnaire (FIQ), the pain visual analogical scale (VAS) and tender point counts were measured. Vascular function was assessed by brachial‐ankle pulse wave velocity (baPWV) and flow‐mediated dilation (FMD). We evaluated the associations between arterial markers and serum TSH, free thyroxin, as well as serum thyroidperoxidase autoantibody (TPO Ab). Results: Patients with a high baPWV (≥ 1490 cm/s) showed more positive TPO Ab (65% vs. 10%, P = 0.006) than those with a normal baPWV. Additionally, the baPWV values of patients with positive TPO Ab were significantly different from those with negative TPO Ab. Age, FIQ and TPO Ab were significantly correlated with baPWV and FMD (all P < 0.05). Multiple linear regression analysis revealed that the only significant predictors of baPWV were age, FIQ and the presence of TPO Ab after adjustment for traditional risk factors. A significant association was also found between FMD and positive TPO Ab. Conclusion: Age, functional status and presence of TPO Ab were significantly associated with increased arterial stiffness in postmenopausal FM patients. Given the combined thyroid autoimmunity in FM patients, a re‐evaluation of the effects on the vasculature may be necessary. [ABSTRACT FROM AUTHOR]

The morphological development of the thyroid gland of pejerrey Odontesthes bonariensis during larval-juvenile transition was studied and related to whole-body concentrations of thyroxine (T4) and tri-iodothyronine (T3). A complementary (c)DNA fragment of the thyroid-stimulating hormone β-subunit ( tshb) was sequenced and transcript levels quantified during this period. Follicles with eosinophilic and T4-immunoreactive colloids were detected at hatching together with tshb transcript levels and whole-body concentrations of T4 and T3 hormones. Thyroid follicles were located in the subpharyngeal region associated with the ventral aorta below the hyoid bone. Follicle structure switched from the rounded form at hatching to oval in juveniles. Significant increase of follicle number per larva, mean colloidal area and total colloidal area was observed throughout development with maximum values at the end of the larval-juvenile transition. A significant decrease of tshb expression together with a significant increase in T4 and T3 whole-body concentrations was observed prior to achieving the juvenile phenotype. These results are in accordance with a negative feedback regulation of tshb expression by thyroid hormones and a possible association between thyroid hormone levels and the acceleration of metabolic processes necessary to complete metamorphosis. [ABSTRACT FROM AUTHOR]

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid-stimulating hormone (TSH), free thyroxine (T4) (FT4), total triiodothyronine (T3) (TT3), reverse T3 (rT3), thyroid-releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT4/TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), whereas TT3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA. The high expression of FRα in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD. [ABSTRACT FROM AUTHOR]