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Background This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. Methods This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. Results The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. Conclusion In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Background To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice. Methods This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). Results Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). Conclusion Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Thyroid hormones are a fundamental part of the maintenance of homeostasis, it is particularly related to cardiovascular function. Clinical or subclinical dysthyroid states can significantly compromise this system during surgical procedures. There are multiple drugs that can modify the thyroid pathology to a greater or lesser extent, reducing the risk of complications in the event of surgery. The use of general anesthesia, whether balanced or total intravenous, has become the Gold standard, due to the lower rate of associated complications. During the perioperative period, strict monitoring of cardiovascular function must be maintained to detect alterations early and initiate the necessary corrections. [ABSTRACT FROM AUTHOR]

Objective: The variability of thyroid function tests (TFTs) during antithyroid drug (ATD) therapy and its association with adverse health outcomes have not been previously studied. The aim of this study was to evaluate the association of TFT variability and cardiovascular morbidity during ATD therapy. Design: Retrospective cohort study. Patients and Measurements: Hyperthyroid patients (n = 394) treated with ATD therapy at Tampere University Hospital between March 2016 and December 2018 were followed up for a median time of 1.5 years (interquartile range 0.8–2.0). The coefficients of variation (CVs) of the follow‐up thyroid‐stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) measurements were determined. The associations of TFT variability and baseline clinical factors with cardiovascular disease (CVD) ‐associated hospital visits were assessed with logistic regression analyses. Results: In the multivariable analyses, age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.03–1.09), male gender (OR: 2.33, 95% CI: 1.03–5.28) and fT4‐CV (OR: 1.02, 95% CI: 1.01–1.04) were independent risk factors for cardiovascular morbidity, whereas baseline positive thyrotropin receptor antibodies (TRAbs) were associated with lower cardiovascular morbidity (OR: 0.29, 95% CI: 0.14–0.61). When the patients with baseline TRAb positivity were studied separately, fT4‐CV was associated with cardiovascular morbidity (OR: 1.03, 95% CI: 1.00–1.05). Conclusions: During ATD therapy, fT4 variability is associated with an increased cardiovascular morbidity. Although positive TRAbs are associated with a lower cardiovascular morbidity compared with hyperthyroidism with negative autoantibodies, the variability of fT4 is associated with cardiovascular morbidity also in patients with positive TRAbs. [ABSTRACT FROM AUTHOR]

Hyperthyroidism is commonly seen in primary care settings. However, the management of hyperthyroidism might be unclear to primary care doctors. Various guidelines have been published to assist clinicians in the management of thyroid disorders at various levels of care. The extensive coverage of these guidelines may not appeal to busy clinicians, and the guidelines do not focus on often resource-limited primary care settings. In this article, we aim to describe a practical guide for managing hyperthyroidism in primary care settings using an ABC approach. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is among the most prevalent organ-specific diseases and is one of the most common causes of hyperthyroidism in regions with normal iodine supply. Current therapeutic strategies for the treatment of patients with GD include antithyroid drugs (ATD), thyroid ablation with radioiodine and surgery, which of them is associated with certain risks of complications. The main task of the doctor is to choose the most optimal method to achieve stable remission. In this regard, much attention is paid to the study of predictors of remission, especially after antithyroid drug treatment due to their widespread use as initial therapy. This article is devoted to the consideration of prognostic factors for Graves' disease remission after antithyroid drug treatment.

Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort. Specifically, we evaluated TRβ antagonism of chemical mixtures extracted from wristbands (n = 72) worn by adults in central North Carolina participating in a case-control study on papillary thyroid cancer. Sections of wristbands were solvent-extracted and analyzed via mass spectrometry to quantify a suite of semivolatile chemicals. A second extract from each wristband was used in a bioassay to quantify TRβ antagonism in human embryonic kidney cells (HEK293/17) at concentrations ranging from 0.1 to 10% of the original extract (by volume). Approximately 70% of the sample extracts tested at a 1% extract concentration exhibited significant TRβ antagonism, with a mean of 30% and a range of 0-100%. Inhibited cell viability was noted in >20% of samples that were tested at 5 and 10% concentrations. Antagonism was positively associated with wristband concentrations of several phthalates, organophosphate esters, and brominated flame retardants. These results suggest that personal passive samplers may be useful in evaluating the bioactivities of mixtures that people contact on a daily basis. We also report tentative associations between thyroid receptor antagonism, chemical concentrations, and papillary thyroid cancer case status. Future research utilizing larger sample sizes, prospective data collection, and measurement of serum thyroid hormone levels (which were not possible in this study) should be utilized to more comprehensively evaluate these associations.

Purpose To evaluate the characteristics and frequency of remission in pediatric patients with Graves’ disease (GD) treated with antithyroid drug (ATD) and to identify factors that may be associated with relapse. Methods Medical records of patients younger than 19 years who presented to the Department of Pediatrics of Queen Elizabeth Hospital Hong Kong with newly diagnosed GD from 1st January 2007 to 31st December 2017 were retrospectively reviewed. Remission was defined as euthyroidism for 12 months or more after discontinuation of ATD treatment and no relapses during the follow-up period. Patients who successfully achieved remission were compared to those who suffered relapse. Factors that may predict occurrence of relapse after ATD treatments were studied, and their odds ratios (ORs) were calculated. Results A total of 101 patients was included in this study. Eighty-one patients completed one course of ATD. Eighteen patients (17.8%) successfully achieved remission, and 58 patients (57.4%) experienced relapse after discontinuation of ATD. The remission group received a significantly longer course of ATD therapy than the relapse group (median, 28 months; interquartile range [IQR], 18–48 months in remission group vs. median, 21 months; IQR, 17–26; p=0.024). The OR for relapse was 0.971 (95% confidence interval [CI], 0.946–0.997) in univariate analysis and remained significant after adjustments in the multivariate regression model (OR, 0.961; 95% CI, 0.933–0.989; p=0.008). Conclusions The remission rate in pediatric patients with GD treated with ATD was low. A longer ATD course was associated with a greater chance of remission in this population.

High throughput in vitro, in silico, and computational approaches have identified numerous environmental chemicals that interfere with thyroid hormone (TH) activity, and it is posited that human exposures to such chemicals are a contributing factor to neurodevelopmental disorders. However, whether hits in screens of TH activity are predictive of developmental neurotoxicity (DNT) has yet to be systematically addressed. The zebrafish has been proposed as a second tier model for assessing the in vivo DNT potential of TH active chemicals. As an initial evaluation of the feasibility of this proposal, we determined whether an endpoint often used to assess DNT in larval zebrafish, specifically photomotor behavior, is altered by experimentally induced hyper- and hypothyroidism. Developmental hyperthyroidism was simulated by static waterborne exposure of zebrafish to varying concentrations (3-300 nM) of thyroxine (T4) or triiodothyronine (T3) beginning at 6 h post-fertilization (hpf) and continuing through 5 days post-fertilization (dpf). Teratogenic effects and lethality were observed at 4 and 5 dpf in fish exposed to T4 or T3 at concentrations >30 nM. However, as early as 3 dpf, T4 (> 3 nM) and T3 (> 10 nM) significantly increased swimming activity triggered by sudden changes from light to dark, particularly during the second dark period (Dark 2). Conversely, developmental hypothyroidism, which was induced by treatment with 6-propyl-2-thiouracil (PTU), morpholino knockdown of the TH transporter mct8, or ablation of thyroid follicles in adult females prior to spawning, generally decreased swimming activity during dark periods, although effects did vary across test days. All effects of developmental hypothyroidism on photomotor behavior occurred independent of teratogenic effects and were most robust during Dark 2. Treatment with the T4 analog, Tetrac, restored photomotor response in mct8 morphants to control levels. Collectively, these findings suggest that while the sensitivity of photomotor behavior in larval zebrafish to detect TH disruption is influenced by test parameters, this test can distinguish between TH promoting and TH blocking activity and may be useful for assessing the DNT potential of TH-active chemicals.

ABSTRACT Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves’ disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves’ hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusions: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Objective: This study aimed at observing the prognostic factors for Graves' disease (GD) recurrence after treatment with antithyroid drugs. Patients and Methods: Clinical data for 247 patients with primary GD hyperthyroidism diagnosed in the endocrinology department of our hospital between March 2014 and February 2017 were collected. Age, sex, thyroid size, thyroid hormone levels, thyrotropin receptor antibody (TRAb), thyroglobulin antibody, thyroid peroxidase antibody, urinary iodine, and other prognostic factors before and after treatment were analyzed and compared. Results: After ATD treatment, 151 cases were in remission and 96 cases were not. The mean age at diagnosis was 37.3 ± 14.0 years in the remission group and 31.2 ± 12.2 years in the nonremission group (P = 0.032). The levels of free triiodothyronine (FT3) in the nonremission group and remission group were 25.7 ± 8.4 and 18.3 ± 9.1 pmol/L, respectively. The proportion of patients with goiter and thyroid-associated orbitopathy was higher in the nonremission group than the remission group. Similarly, both the FT3/FT4 ratio (4.63 ± 1.08 and 3.72 ± 0.69, P = 0.020) and TRAb level (27.4 ± 10.7% and 18.1 ± 9.8%, P = 0.001) significantly increased. Logistic regression analysis indicated that high thyroid volume (odds ratio [OR] =9.647, P = 0.003), high free T3/free T4 ratio (OR = 1.541, P = 0.019), and TRAb level (OR = 1.317, P = 0.002) were independent factors influencing drug treatment failure and were associated with poor prognosis. After drug withdrawal, patients with distinctly enlarged thyroid glands, thyroid-associated eye disease, and low serum thyroid-stimulating hormone (sTSH) levels were higher in the nonremission group than in the remission group. Conclusion: GD patients with goiter, high TRAb level and high FT3/FT4 ratio had poor poor response to drugs. The recurrence rate was high in patients with thyroid-related eye disease, and sTSH delayed recovery. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristics and frequency of remission in pediatric patients with Graves' disease (GD) treated with antithyroid drug (ATD) and to identify factors that may be associated with relapse. Methods: Medical records of patients younger than 19 years who presented to the Department of Pediatrics of Queen Elizabeth Hospital Hong Kong with newly diagnosed GD from 1st January 2007 to 31st December 2017 were retrospectively reviewed. Remission was defined as euthyroidism for 12 months or more after discontinuation of ATD treatment and no relapses during the follow-up period. Patients who successfully achieved remission were compared to those who suffered relapse. Factors that may predict occurrence of relapse after ATD treatments were studied, and their odds ratios (ORs) were calculated. Results: A total of 101 patients was included in this study. Eighty-one patients completed one course of ATD. Eighteen patients (17.8%) successfully achieved remission, and 58 patients (57.4%) experienced relapse after discontinuation of ATD. The remission group received a significantly longer course of ATD therapy than the relapse group (median, 28 months; interquartile range [IQR], 18-48 months in remission group vs. median, 21 months; IQR, 17-26; P=0.024). The OR for relapse was 0.971 (95% confidence interval [CI], 0.946-0.997) in univariate analysis and remained significant after adjustments in the multivariate regression model (OR, 0.961; 95% CI, 0.933-0.989; P=0.008). Conclusion: The remission rate in pediatric patients with GD treated with ATD was low. A longer ATD course was associated with a greater chance of remission in this population. [ABSTRACT FROM AUTHOR]

Background Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Hyperthyroidism is commonly seen in primary care settings. However, the management of hyperthyroidism might be unclear to primary care doctors. Various guidelines have been published to assist clinicians in the management of thyroid disorders at various levels of care. The extensive coverage of these guidelines may not appeal to busy clinicians, and the guidelines do not focus on often resource-limited primary care settings. In this article, we aim to describe a practical guide for managing hyperthyroidism in primary care settings using an ABC approach.

Background The aim of this study was to investigate the changes in vital signs and hemodynamic status that occur in patients during the intraoperative course of thyroidectomy in Graves’ Disease (GD). Methods A total of 71 patients were included in the study. Patients were directed to surgery when they had large goiters with compressive symptoms or suspicious nodules, were pregnant or lactating, were unresponsive or intolerant to antithyroid drugs (ATDs), or expressed a preference to have surgery. All patients scheduled for operations underwent surgery while in the euthyroid state. Results Hemodynamic instability was observed in 18 patients during thyroidectomy. Disease duration, sample weight, and thyroid-stimulating hormone receptor antibodies (TRAb) levels were found to be effective on hemodynamic instability. Logistic regression analysis revealed an 11-fold increase in the instability risk in patients with a period of disease shorter than 21 months (P = 0.037). A TRAb value >11.5 increased the risk by 235fold (p

Background The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. Methods The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. Results A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). Conclusion The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Graves' hyperthyroidism is characterized by stimulation of the thyroid gland by thyroid-stimulating hormone receptor antibodies (TRAbs). Antithyroid drug (ATD) continuation is recommended as long as the thyroid gland is stimulated. Goiter size, thyroidal 123I uptake, serum thyroglobulin level, and TRAb positivity are reliable markers of thyroid stimulation. Attention must also be paid to the responsiveness of the thyroid gland due to the high prevalence of painless thyroiditis and spontaneous hypothyroidism during treatment. TRAbs disappeared at <5 years entering remission in 36.6% of patients (smooth-type), while re-elevation of TRAb activity occurred in 37.7% (fluctuating-type) and remained positive for >5 years in 21.1% (smoldering-type). Seven percent of patients remained positive for TRAbs for >30 years, requiring life-long ATD treatment. Remission occurred after median 6.8 years (interquartile range, 4.0 to 10.9) of ATD treatment in 55% of patients. However, late relapse may occur after stressful events (dormant type). In apparently intractable Graves' disease (GD) with a large goiter (>40 g), 131I therapy should be considered. For initial and long-term ATD treatment, we must choose effective, safe, and economical drugs such as 100 mg potassium iodide (KI), although KI sensitivity varies in patients with GD. Thionamide, which has notorious side effects, is added only during the KI-resistant period.

Graves’ disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves’ disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.

The aim of this study was to investigate the changes in vital signs and hemodynamic status that occur in patients during the intraoperative course of thyroidectomy in Graves' Disease (GD). A total of 71 patients were included in the study. Patients were directed to surgery when they had large goiters with compressive symptoms or suspicious nodules, were pregnant or lactating, were unresponsive or intolerant to antithyroid drugs (ATDs), or expressed a preference to have surgery. All patients scheduled for operations underwent surgery while in the euthyroid state. Hemodynamic instability was observed in 18 patients during thyroidectomy. Disease duration, sample weight, and thyroid-stimulating hormone receptor antibodies (TRAb) levels were found to be effective on hemodynamic instability. Logistic regression analysis revealed an 11-fold increase in the instability risk in patients with a period of disease shorter than 21 months (P = 0.037). A TRAb value >11.5 increased the risk by 235fold (p < 0.001). High levels of TRAb values and new onset of disease with shorter periods of ATDs use may be risk factors for hemodynamic instability during thyroidectomy. Patients with larger thyroid glands are at greater risk for instability during surgery. Those risks should be taken into account during surgery, and the surgical and anesthetic management of the patient should be made more carefully in concordance with the anesthesia team. [ABSTRACT FROM AUTHOR]