Baseline Thyroid Function Research Articles

The effect of cardiac catheterization on thyroid functions in infants with congenital heart diseases: a prospective observational study

This study aims to determine the incidence, clinical course, and risk factors of hypothyroidism following cardiac catheter (CC) in infants with congenital heart diseases (CHD). This prospective study involved 115 patients with CHD, all aged 3 years or younger, who underwent CC, as well as 100 healthy age- and sex-matched controls. Baseline thyroid function tests (TFTs) were conducted for both the patients and controls. In the CHD cohort, TFTs were reassessed 4 weeks after the CC, and for those with abnormal TFT values at this time, the tests were repeated after 2 weeks. Levothyroxine was started for patients with persistent abnormal TFTs, at 4 weeks and 6 weeks assessments after CC. Four weeks after CC, 12% of the studied group exhibited hypothyroidism. Univariate analysis identified significant predictors of hypothyroidism following CC: aortic stenosis (RR = 10.0 (1.49–66.99), P = 0.018), duration of fluoroscopy during CC (RR = 2.12 (0.99–4.26), P = 0.05), and total iodinated contrast media (iCM) during CC (RR = 2.5 (1.35–3.55), P = 0.019). Multivariate analysis indicated that iCM dose was the sole significant predictor of developing hypothyroidism (RR = 2.10 (1.01–3.23), P = 0.04). ROC curve analysis showed that the cut-off point of iCM dose for prediction of hypothyroidism evolution is 8.7 gm/kg, (sensitivity: 83%, specificity: 65%), while the cut-off point of fluoroscopy duration which predicts the development of hypothyroidism is 24 min (sensitivity: 83%, specificity: 66%). Acquired hypothyroidism after CC persisted in 4% of this cohort for 6 months.Conclusion: Higher doses of iCM and longer duration of fluoroscope during CC are risk factors for the evolution of hypothyroidism post-CC. We recommend assessing thyroid profile 4 weeks after CC, particularly in patients who received an iCM dose greater than 8.7 gm/kg and/or exposed to fluoroscopy for more than 24 min. What is known:• The use of excess iodine leads to transient inhibition of thyroid hormones biosynthesis via the Wolff-Chaikoff effect.• Infants with congenital heart diseases (CHD) are more prone to hypothyroidism due to higher frequency of abnormal thyroid morphology and routine exposure to supraphysiological doses of iodine.What is new:• Exposure to a total dose of iodinated contrast media more than 8.7 gm/kg and a fluoroscopy duration more than 24 min during cardiac catheter are risk factors for the evolution of thyroid hypofunction following cardiac catheter.

Subclinical hypothyroidism: a new predictor of heart failure with improved ejection fraction in HFrEF patients.

Heart failure (HF) with improved ejection fraction (HFimpEF) has gradually attracted widespread attention in recent years for its better clinical prognosis. In this study, we attempted to investigate the relationship between subclinical hypothyroidism (SCH) and HFimpEF. This study retrospectively collected clinical data on patients with HF with reduced ejection fraction (HFrEF) hospitalized at the First Affiliated Hospital of USTC from March 2015 to September 2023, and divided into two groups as euthyroidism or SCH according to the baseline thyroid function. Then patients were further categorized into HFimpEF (follow-up LVEF > 40% and absolute increase ≥ 10%) and persistent HFrEF based on their LVEF on the echocardiograms during the follow-up period. Afterward, logistic regression was used to estimate the effect of SCH on HFimpEF. A total of 916 patients with HFrEF met the inclusion and exclusion criteria, and 396 patients (43.2%) progressed to HFimpEF status during the follow-up period. Compared with HFrEF patients, the prevalence of SCH is lower in HFimpEF patients (9.3% vs. 14.4%, P = 0.020). Univariate logistic regression analysis indicates that SCH was a potential predictor for HFimpEF (OR: 0.612 [95% CI 0.403-0.928], P = 0.021). After adjusting for multiple factors in logistic regression, the odds ratios of HFrEF patients with SCH progressing to HFimpEF decreased by 37.8% (OR: 0.622 [95% CI 0.397-0.974], P = 0.038) compared with patients with euthyroidism. This study suggests that thyroid function affects the improvement of cardiac function in patients with HFrEF and SCH is an independent predictor for HFimpEF.

Longitudinal Assessment of FT3 to FT4 Conversion Ratio in Predicting the Efficacy of First-Line Pembrolizumab-Based Therapy in Advanced Non-Small Cell Lung Cancer: A Propensity-Score Matching Analysis of Data from the National Drug Monitoring Agency.

Baseline thyroid function, as measured by the fT3 to fT4 ratio, has been shown to influence the prognosis of advanced cancer patients receiving active treatments. Although immune checkpoint blockade can alter the balance of thyroid hormones, this interaction has not been thoroughly investigated. The present research sought to determine whether changes in the fT3/fT4 ratio could affect the survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) who were undergoing pembrolizumab-based therapies. This study included patients with metastatic NSCLC who received pembrolizumab as upfront treatment, either alone or in combination with platinum-based chemotherapy. Relevant data were gathered before the start (time point 1) and after 12 weeks (time point 2) of treatment. From April 2018 to May 2023, we enrolled 258 eligible patients, 156 (60.5%) and 102 (39.5%) of whom were treated with single-agent or combination therapy, respectively. We stratified patients into two groups based on baseline fT3 and fT4 values [euthyroid cohort defined by fT3 and fT4 both within the normal range vs. euthyroid sick syndrome cohort defined by low fT3 and/or fT4 levels]. We examined the differences in progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. After applying propensity-score matching, we considered 88 relevant cases in each cohort. Longitudinal comparison of fT3/fT4 ratios showed a significant increase in the median value after pembrolizumab-based therapy (p < 0.001). We computed ROC curves to analyze the correlation between fT3/fT4 ratios and survival outcomes. The relative AUC values were not viable in predicting a positive outcome at the first time point. Conversely, assessment at the second time point revealed a significant association with PFS [AUC 0.82 (95% CI 0.75-0.89), p < 0.001] and OS [AUC 0.81 (95% CI 0.75-0.88), p < 0.001]. After a median follow-up of 20.2 (95% CI 16.2-24.2) months, the median PFS for the low and high fT3/fT4 ratio groups was 4.1 (95% CI 3.0-5.1) and 15.3 (95% CI 10.3-20.1) months, respectively (p < 0.001). The median OS for the low and high fT3/fT4 ratio groups was 6.7 (95% CI 4.9-8.5) and 19.6 (95% CI 16.4-22.8) months, respectively (p < 0.001). The multivariate analysis revealed that a low fT3/fT4 ratio was independently associated with shorter PFS [HR 2.51 (1.66-3.78); p < 0.001] and OS [HR 2.18 (1.43-3.34); p < 0.001]. After the optimal weighting of prognostic factors according to thyroid function impairment, the fT3/fT4 ratio at baseline did not affect the survival of patients receiving immune checkpoint blockade for advanced NSCLC. Patients with an increased fT3/fT4 ratio experienced a significantly decreased risk of disease progression and mortality. The longitudinal assessment of fT3/fT4 ratio may play a predictive role in this specific therapeutic setting.

Effects of Metformin Therapy on Thyroid Volume and Functions in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Single-center Prospective Study.

Patients with impaired glucose metabolism have increased thyroid volume and a higher prevalence of nodules. Yet, some studies show that there is an improvement in these thyroid parameters after diabetes treatment. Our observational study aimed to reveal the effect of treatment on thyroid function, thyroid volume, and the presence of nodules in newly diagnosed type 2 diabetes mellitus (T2DM) patients who were started on metformin treatment. Euthyroid and subclinically hypothyroid patients with a serum TSH level of <10 mU/L, who were newly diagnosed with T2DM and started on metformin as an antidiabetic treatment and not used any thyroid medication previously, were included in our study. Patients' characteristics were recorded. Baseline and 6th-month serum thyroid function tests were scheduled. Baseline and 6th-month thyroid gland characteristics were examined by thyroid ultrasonography. A total of 101 (37 males, 64 females) newly diagnosed T2DM patients with euthyroid (n=95) or subclinical hypothyroidism (n=6) were included in the study. The mean age of the patients was 53.02 ± 11.9 years, and the mean BMI was 29.60 ± 3.9 kg/m2. Fifty-two (52%) patients were classified as obese. Body weight, BMI, serum TSH, ALT, Anti-TPO levels, and thyroid volume decreased significantly in the 6th-month compared to baseline values (p = 0.000; p = 0.000; p = 0.011; p = 0.022; p = 0.000, respectively). Serum anti-Tg, fT4, fT3 levels, and thyroid nodule count did not change significantly. A high agreement was found between the baseline and 6thmonth nodule counts (gamma= 0.886; p < 0.001) and the presence of multi-nodularity in the thyroid (gamma= 0.941; p < 0.001), but no significant change was observed. Anti-TPO levels showed a significant decrease in both with and without obesity groups at the end of 6 months (p = 0.003, p = 0.009, respectively). Serum TSH level decreased significantly only in non-obese subjects (p = 0.004), and thyroid volume decreased significantly only in obese subjects (p = 0.000). Our results suggest that metformin treatment significantly reduces body weight, BMI, thyroid volume, and serum TSH, ALT, and Anti-TPO levels in patients with newly diagnosed T2DM. Moreover, serum TSH levels showed a significant decrease in non-obese subjects, while thyroid volume showed a significant decrease in obese subjects.

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024

Effect of Rehabilitation Training for Pregnancy Outcomes and Postpartum Quality of Life in Thyroid Cancer Survivors: A Propensity Score-Matched Cohort Study

Background: This retrospective cohort study aimed to evaluate the impact of exercise intervention, specifically combined aerobic and resistance training, on the quality of life, mental health, and pregnancy outcomes of women with a history of treated papillary thyroid cancer, particularly those who underwent radioactive iodine therapy. Methods: The study is a propensity score-matched cohort study. The cohort was divided into observation and controls based on the presence or absence of thyroid cancer history and adherence to exercise intervention. Propensity score matching was employed for comparable group creation. Exercise interventions were initiated between the 16th and 20th week of gestation, lasting at least 16 weeks. Baseline information, thyroid function, maternal outcomes, neonatal outcomes, and quality of life were assessed. Statistical analyses included subgroup analyses based on age. Results: A total of 4432 women were initially included, with 84 in the observation group and 3114 in the control group after exclusions. Following post-matching, a total of 252 participants contributed data to our study. However, post-intervention observations revealed that participants exhibited elevated anxiety levels (45.81 ± 10.66 vs. 39.72 ± 12.79, p = 0.006), along with decreased placental weight (562.10 ± 64.45 vs. 581.02 ± 65.20, p = 0.007). Older mothers (&gt;35 years) in the survivor group showed a higher risk of anemia (p = 0.005), subgroup analysis revealed significant differences in the incidence of anemia among older mothers. Conclusions: Exercise intervention, specifically combined aerobic and resistance training, is considered safe for pregnant women with treated papillary thyroid cancer, enhancing pregnancy status without adversely affecting outcomes. While anxiety levels may persist postpartum, exercise interventions do not worsen pregnancy outcomes. Attention is warranted for the increased risk of anemia in older mothers following exercise intervention. Despite limitations, this study contributes valuable insights for the care of thyroid cancer survivors during pregnancy.

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

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

Association of thyroid peroxidase antibody positivity in the first trimester with gestational metabolic disorders: a retrospective study

Objective To investigate the association between thyroid peroxidase antibody (TPOAb) positivity in the first trimester and maternal metabolic syndrome in pregnancy. Methods The study retrospectively reviewed the medical records for 787 pregnant women. Serum-free thyroid hormone, thyroid stimulating hormone, and TPOAb levels were measured in early pregnancy (<13 weeks gestation). Baseline demographics, clinical characteristics, thyroid function, and pregnancy outcomes were compared between women who were TPOAb positive or TPOAb negative in the first trimester. Associations between TPOAb positivity in the first trimester and the occurrence of gestational diabetes mellitus, hypertensive disorders complicating pregnancy (HDCP), maternal metabolic syndrome in pregnancy, and adverse pregnancy outcomes were explored. Results Data for 787 women with a singleton pregnancy were included in the analyses. In women who were TPOAb positive compared to TPOAb negative in the first trimester, baseline HDL-C was significantly lower (1.51 [1.33, 1.81] vs. 1.62 [1.40, 1.87], p = 0.028), and there was a significantly higher incidence of HDCP (15.8% vs. 6%, p < 0.0001), maternal metabolic syndrome in pregnancy (18.8% vs 6.4%, p < 0.0001) or preeclampsia (7% vs, 2.5%, p = 0.024). There was a significant nonlinear association between TPOAb levels in the first trimester and the incidence of HDCP or maternal metabolic syndrome in pregnancy (both p < 0.001). The logit of the probability of having HDCP or maternal metabolic syndrome in pregnancy increased rapidly at TPOAb (log10) ≤ 1.5 (TPOAb (log10) = 1.07 as reference). After adjusting for confounders (maternal age, pre-pregnancy BMI, gravidity, parity and history of adverse events during pregnancy), there was a significantly higher risk of HDCP (odds ratio [OR], 3.029; 95% confidence interval [CI], 1.586, 5.622, p = 0.001), maternal metabolic syndrome in pregnancy (OR, 2.841; 95% CI, 1.473-5.260, p = 0.001), or preeclampsia (OR 3.315, 95% CI 1.305-7.788, p = 0.008) in women who were TPOAb positive compared to TPOAb negative in the first trimester. Conclusion TPOAb positivity in the first trimester may increase the risk of HDCP, maternal metabolic syndrome in pregnancy, and preeclampsia, emphasizing the need for universal screening for thyroid disorders and better diagnostic criteria and management strategies for metabolic disorders during pregnancy.

Abstract 16324: A Deep Learning Electrocardiogram Model Identifies Risk of Incident Heart Failure in Patients With Subclinical Hypothyroidism

Introduction: Subclinical hypothyroidism (SH) is associated with an increased risk of heart failure (HF). However, there are no established measures to predict HF development within the SH population. Hypothesis: Risk of incident heart failure in SH can be predicted from a 12-lead electrocardiogram using features extracted by a convolutional neural network-based model. Methods: To test the hypothesis, we developed a convolutional neural network (CNN)-based model to detect ECG features linked with low thyroid function by training to discriminate the presence of hypothyroidism from 10,745 ECGs (2,693 from patients with low free T4 (FT4) and 8,052 from age, sex-matched patients without evidence of low FT4). The model was applied to baseline ECGs from an external cohort of 2,293 patients with SH (defined TSH &gt;4.5mIU/L and FT4 within 0.9-1.9ng/dl) to estimate the cardiac phenotype induced by hypothyroidism (ECG-hypothyroidism score). Cumulative incidences of HF admission were compared between groups stratified by the tertile of the model output (low, intermediate, and high score groups). Adjusted hazard ratios (aHR) were calculated using Cox proportional hazard model. Results: HF admission was more frequent in the high score group (9.60/100 person-year), compared with the intermediate or low score groups (5.08 and 2.29 per 100 person-year in the, respectively; Fig ). Subgroup analyses by sex and age group yielded similar results. The association between the ECG-hypothyroidism score and HF admission remained significant after adjustment for patient characteristics, conventional ECG abnormalities, and baseline thyroid function (high vs low score group: aHR 3.56, [95%CI, 2.26-5.61]; high vs intermediate score group: aHR 1.78, [95%CI, 1.25-2.54]). Conclusions: The CNN-based model, trained to detect prevalent hypothyroidism, accurately identified patients at high risk for HF admission within the SH population using baseline ECG.

FRI483 Changes In Thyroid Function Test With Tirzepatide Use In Patients With Hypothyroidism

Abstract Disclosure: G.K. Yu: None. S. Nakhle, M.D.: None. N.J. Vernetti: None. A. Chao, DO: None. Background: Incretin hormone Glucacon-like peptide-1 receptor agonist (GLP-1RA) has been established to treat type 2 diabetes or obesity. A novel dual-receptor agonist to GIPR/GLP-1R, tirzepatide has been approved for type 2 diabetes mellitus treatment and has shown greater weight loss compared to GLP1-RA. Also, since GLP-1 and GIP have effects on multiple organs/tissue including the gut, tirzepatide may have additional effects on levothyroxine absorption. Method: We retrospectively reviewed the charts of patients with hypothyroidism and newly given prescriptions of tirzepatide (Mounjaro) at our outpatient clinic from July 1, 2022, to Nov 30, 2022. Baseline thyroid function test results and follow-up test results were reviewed. Result: A total of seventy patients’ data were identified and reviewed. Patients with insufficient data, early termination of the therapy, and patients whose levothyroxine doses were adjusted at the same time of tirzepatide initiation were excluded. A total of 17 patients on stable dose of levothyroxine replacement who had lab prior to starting tirzepetide and repeated lab within 4 to 8 weeks after that were found and included in the study. TSH of 5/17 patients (29%) was suppressed below the normal range at 6 weeks. TSH of 11/17 patients (65%) decreased compared to baseline. The mean baseline TSH was 2.288. Repeat test was done in 4-8 weeks, (mean 53.28 days, median 47 days), and mean TSH was 1.569. Conclusion: We were able to review only seventeen patients’ thyroid function tests, but there was TSH reduction in 65 % of patients, and 5(29%) out of 17 patients had suppressed TSH in 6-8 weeks (mean 53.28 days, median 47 days). Our results suggest monitoring TSH early after starting tirzepatide might be necessary to avoid iatrogenic hyperthyroidism. We suspect factors other than weight loss play a role in the thyroid hormone level because of early changes in TSH prior to achieving significant weight loss. Presentation: Friday, June 16, 2023

The prognostic Value of Thyroid Hormone Levels in Immunotherapy-Treated Patients With Metastatic Urothelial Carcinoma.

A low fT3/fT4 ratio has been associated with a poorer prognosis in patients treated for different solid malignancies. However, the prognostic role of baseline thyroid function in patients with metastatic urothelial carcinoma (mUC) has not yet been established. We analyzed 72 consecutive immunotherapy-treated patients with mUC from a single institution. We recorded clinical data, baseline blood test results, and oncological outcomes. We stratified patients into three groups according to the fT3/fT4 ratio value and analyzed differences in progression-free survival (PFS), overall survival (OS), and radiological response in the three groups. We also conducted univariate and multivariate analyses to identify prognostic factors for PFS and OS. The median PFS in the low, intermediate, and high fT3/fT4 ratio groups was 2.2, 4.1, and 8.2 months, respectively (P < 0.01). The median OS in the low, intermediate, and high fT3/fT4 groups was 3.6, 10.3, and 19.1 months, respectively (P < .01). The low fT3/fT4 ratio maintained its prognostic role independently of other prognostic factors. Patients with a high fT3/fT4 ratio had an increased radiological response. Thyroid hormone impairment, as measured by the fT3/fT4 ratio, is a strong prognostic factor in patients treated with immunotherapy for urothelial carcinoma.

Association between thyroid function and regorafenib efficacy in patients with relapsed wild-type IDH glioblastoma: a large multicenter study

PurposeRegorafenib demonstrated encouraging results in recurrent glioblastoma patients. Some studies showed that changes in circulating thyroid hormones (fT3, fT4, fT3/fT4 ratio) can be considered as prognostic factors in patients with various types of tumors. We designed this study to investigate the relationship between baseline thyroid variables and outcome in IDH-wild type GBM patients who were treated with regorafenib.MethodsThis multicenter retrospective study included recurrent IDH-wild-type glioblastoma patients treated with regorafenib. Only patients with baseline thyroid function values (TSH, fT3, fT4, fT3/fT4 ratio) available were evaluated. RANO criteria were used to analyze neuroradiological response. Survival curves were estimated using the Kaplan–Meier method. The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4) and survival (PFS, OS) were investigated with Cox regression models.ResultsFrom November 2015 to April 2022, 134 recurrent IDH-wildtype GBM patients were treated with regorafenib and 128 of these had information on baseline thyroid function value. Median follow-up was 8 months (IQR 4.7–14.0). Objective Response Rate was 9% and Disease Control Rate was 40.9%. Median PFS was 2.7 months (95%CI 2.2–3.6) and median OS was 10.0 months (95%CI 7.0–13.0). Lower baseline TSH value in the blood was correlated with a higher rate of disease progression to regorafenib (p = 0.04). Multivariable analyses suggested a non-linear relationship between PFS (p = 0.01) and OS (p = 0.03) with baseline fT3/fT4 ratio.ConclusionIn recurrent wild-type IDH glioblastoma patients, baseline fT3/fT4 ratio showed a non-linear relationship with survival, with different impacts across the spectrum of fT3/fT4 ratio. Moreover, baseline TSH may be a predictor of regorafenib activity.

Mifepristone-Induced Hypothyroidism.

Medications are known to affect the thyroid physiology and are a known cause of hypothyroidism. There is an ever-growing list of medications that affect the thyroid by 1 or more mechanisms. Mifepristone is presently used for the treatment of mild autonomous cortisol secretion (MACS). Hypothyroidism is not a known side effect of this medication. We present a 71-year-old woman with newly diagnosed impaired fasting glucose, dyslipidemia, and osteopenia presenting with a 3-year history of unintentional 15-pound weight gain (despite exercise and a good diet) and increased anxiety. Her physical examination was pertinent for mild lower extremity edema, easy bruising, and skin thinning. Workup revealed adrenocorticotropic hormone (ACTH)-independent MACS from bilateral micronodular hyperplasia of the adrenals. Since she was not a surgical candidate, medical management with mifepristone was chosen. While on mifepristone, she complained of excessive fatigue, a workup done revealed new-onset hypothyroidism. Given her symptoms and bloodwork, she was started on levothyroxine. After stopping mifepristone, she was biochemically and clinically euthyroid and was eventually off levothyroxine. The mechanism by which mifepristone induces hypothyroidism is unknown. Except for a multicenter case series suggesting that mifepristone increases thyroid hormone requirements in patients with central hypothyroidism, to the best of our knowledge, the literature on euthyroid patients developing hypothyroidism secondary to mifepristone is scarce. In conclusion, while the hypothyroidism seems reversible our case highlights the importance of getting baseline thyroid function tests (TFTs) and repeating them while on the medication. Treatment of hypothyroidism is based on symptoms and bloodwork.

Effect of Inactivated and mRNA COVID-19 Vaccination on Thyroid Function Among Patients Treated for Hyperthyroidism.

Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves' disease and worsening of pre-existing Graves' disease. Little is known about the thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination. Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability. We included consecutive patients treated for hyperthyroidism attending the thyroid clinic at a teaching hospital between January and September 2021. They were categorized into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for the vaccinated group, and the first date of attendance in the inclusion period for the unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in antithyroid drug dosage), whichever was earlier. A total of 910 patients were included (mean age 51.6 years; 82.1% female). Of these, 86.2% had Graves disease and 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (hazard ratio 0.78, 95% CI 0.56-1.09, P = .151); this was consistent in Graves disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering a thyroid storm or difficulty in subsequent thyroid function control. Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19.

PSAT264 Effectiveness of Thyroid Gland Size Determination by Ultrasonography versus Manual Palpation in Success of Radioactive Iodine Therapy for Graves’ Disease

Abstract Background Thyroid gland size is a required parameter for radioactive iodine (RAI) dose calculation for radioactive iodine therapy (RAIT) of Graves’ disease. Comparing between ultrasonography and palpation, previous studies showed that the former provided more accurate thyroid sizes. However, there have been no studies comparing success of RAIT when either of these two methods is used to determine thyroid gland size. The aim of this study is to evaluate the outcome of RAIT using thyroid gland size measured by ultrasonography compared with palpation for RAI dose calculation. Methods We prospectively enrolled Graves’ disease patients who presented for the first RAIT. Thyroid gland sizes of all participants were determined by both ultrasonography and palpation on the day of RAIT. Participants were then randomized into ultrasound (US) or palpation groups for which RAI dose administered was calculated using the thyroid size obtained by the method assigned to their groups. Primary outcome was success of RAIT at 6 months, defined by the ability to discontinue antithyroid drugs (ATDs). Secondary outcomes were factors associated with success of RAIT. Results One hundred patients completed the study, 52% were in the US group and 42% were in the palpation group. Success rate of RAIT at six months was higher in the palpation group (58.3% vs 38.5%, p = 0.047). Among patients who had successful RAIT, the palpation group had a higher rate of hypothyroidism than did US group (78.6% vs 60%) as well as higher RAI dose (9.5 ± 3.6 millicuries in palpation group vs 7.1 ± 4.8 millicuries in US group, p = 0.005). There were no factors associated with favorable outcome, including sex; age; weight; type or dose of previous ATDs; duration of disease; baseline thyroid function tests; baseline anti-TSH receptor antibody levels and urine iodine. There was a poor correlation between thyroid sizes, obtained by ultrasonography and palpation (correlation coefficient = 0.578). The least discrepancy in size was observed when thyroid glands were between 40 and 60 grams (g). The highest difference was seen in patients with thyroid sizes &amp;lt;20 g when the sizes were overestimated by palpation. Conclusion Success of RAIT was higher in palpation group than in US group. Overestimation of thyroid gland size accounted for the higher RAI dose and success of palpation group at the expense of more hypothyroidism. Low constant value per gram of thyroid tissue in the calculation formula might underlie the overall low success rate. Palpation tended to incorrectly estimate the size when thyroid gland is either small (&amp;lt;20 g) or large (&amp;gt;=60 g). Therefore, adequate constant value in the calculation formula and obtaining thyroid gland size by ultrasonography prior to RAIT in patients with extreme thyroid sizes may be beneficial. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Long-Term Thyroid Function Outcome after Head and Neck Radiotherapy: External Validation and Comparisons of Thyroid Gland Dose-Volume Constraints

<h3>Purpose/Objective(s)</h3> Primary hypothyroidism is a common late complication in patients who underwent head and neck radiotherapy, occurring at incidences as high as 20-50% among long-term survivors. Various radiation dose-volume constraints for the thyroid gland have been proposed in retrospective series, but none has been externally validated for predicting long-term thyroid function outcome. <h3>Materials/Methods</h3> We undertook a systematic review of the literature and identified 22 distinct radiation dose-volume constraints of the thyroid gland for head and neck radiotherapy planning. We reviewed the thyroid gland dosimetry of 488 consecutive head and neck cancer patients who had normal baseline thyroid function and underwent definitive radiotherapy between January 2013 and December 2015 in two tertiary oncology centers. Thyroid function was monitored at least yearly after radiotherapy. Primary hypothyroidism was defined as serum TSH levels above the upper limit of normal. Time to hypothyroidism was estimated using cumulative incidence function with death designated as a competing event. Univariable and multivariable analyses were conducted using Gray's test the Fine-Gray sub-distribution hazard model. Diagnostic performances of the 22 constraints were compared using time-dependent receiver operating characteristic curves. <h3>Results</h3> With a median follow-up of 6.8 years, 205 (42.0%) patients developed post-radiation primary hypothyroidism. The 5-year primary hypothyroidism rate was 30.5%. Among all candidate dose-volume parameters (Dmin, Dmax, Dmean, V25, V30, V30, V35, V40, V45, V50, V30-60, VS45 and VS60), thyroid volume spared from 60Gy (VS60) had the largest areas under curve of 0.715, 0.694 and 0.698, at 1 year, 3 years and 5 years after radiotherapy, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for VS60 ≥10cc on 5-year hypothyroidism risk were 84.4%, 40.3%, 38.5% and 85.4%, respectively. Among all evaluated constraints, VS60 ≥10cc had the highest F-score of 0.59, suggesting a superior overall diagnostic accuracy. The 5-year hypothyroidism risk for patients with thyroid VS60 ≥10cc and VS60 <10cc were 14.7% and 38.2%, respectively (p <0.001). In multivariate regression, young age, VS60 <10cc and small thyroid volume and were independent predictors for post-radiation primary hypothyroidism. The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 <10cc was 2.00 (95% C.I., 1.33 – 3.07; p <0.001). <h3>Conclusion</h3> Our external validation study identified thyroid VS60 as the best radiation dose-volume parameter to predict long-term thyroid gland function in patients who underwent head and neck radiotherapy. VS60 >10cc is a potentially useful constraint that limits 5-year primary hypothyroidism risk to below 15%. As far as it is feasible during radiotherapy optimization, higher VS60 targets should be considered to further reduce the risk of this late complication among head and neck cancer patients.

The SELFI Study: Iodine Excess and Thyroid Dysfunction in Women Undergoing Oil-Soluble Contrast Hysterosalpingography.

Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates. However, OSCM has high iodine content and long half-life, leading to potential iodine excess. This work aimed to determine the pattern of iodine excess after OSCM HSG and the effect on thyroid function. A prospective cohort study was conducted of 196 consecutive consenting eligible women without overt hypothyroidism or hyperthyroidism. All completed the study with compliance greater than 95%. Participants underwent OSCM HSG (Auckland, 2019-2021) with serial monitoring of thyrotropin (TSH), free thyroxine (FT4), and urine iodine concentration (UIC) for 24 weeks. The main outcome measure was the development of subclinical hypothyroidism (SCH), defined as a nonpregnant TSH greater than 4 mIU/L with normal FT4 (11-22 pmol/L) in those with normal baseline thyroid function. Iodine excess (UIC ≥ 300 μg/L) was almost universal (98%) with UIC peaking usually by 4 weeks. There was marked iodine excess, with 90% and 17% of participants having UIC greater than or equal to 1000 μg/L and greater than 10 000 μg/L, respectively. Iodine excess was prolonged with 67% having a UIC greater than or equal to 1000 μg/L for at least 3 months. SCH developed in 38%; the majority (96%) were mild (TSH 4-10 mIU/L) and most developed SCH by week 4 (75%). Three participants met the current treatment guidelines (TSH > 10 mIU/L). Thyroxine treatment of mild SCH tended to improve pregnancy success (P = .063). Hyperthyroidism (TSH < 0.3 mIU/L) occurred in 9 participants (5%). OSCM HSG resulted in marked and prolonged iodine excess. SCH occurred frequently with late-onset hyperthyroidism occasionally. Regular thyroid function tests are required for 6 months following this procedure.

P11.20.A Correlation between thyroid function and regorafenib activity in recurrent IDH wild-type(IDHwt) glioblastoma(GBM) patients: a large monocentric study

Abstract Background Glioblastoma is the most frequent CNS malignant tumor, with high aggressiveness and poor prognosis. Regorafenib has recently demonstrated promising activity in terms of survival in recurrent glioblastoma patients. The impact of thyroid function on regorafenib activity has alreasy described in in patients with other types of tumors. This study aimed to investigate the relationship between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and survival in IDHwt GBM patients who were treated with regorafenib. Material and Methods We retrospectively evaluated all consecutive recurrent IDHwt GBM patients who were treated with regorafenib at the Veneto Institute of Oncology in Padua (Italy) for which baseline thyroid function assessment was available prior to starting regorafenib. Major inclusion criteria were: histological diagnosis of IDHwt glioblastoma, regorafenib as second-line treatment, basel thyroid values available.The relationships between baseline thyroid variables (TSH, fT3, fT4, fT3/fT4 ratio) and outcomes (PFS, OS) were investigated with Cox regression models, where thyroid variables were modeled with first order polynomial or restricted cubic splines. Results We enrolled 108 recurrent IDHwt glioblastoma patients treated with regorafenib at our center From November 2015 to January 2022: 70% were male and median age was 50 years old. All patients received post-surgical treatment with concomitant chemotherapy and subsequent temozolomide according to Stupp protocol as first-line therapy. 32 patients (30%) underwent a second surgery upon recurrence. From starting regorafenib the median follow-up was 7.3 months (IQR 4.0-12.7). MedianPFS was 2.2 months (95% CI 2.0 to 3.4), and PFS rate was 43-13-4% at 3-6-12ms, respectively. MedianOS was 10.4 months (95% CI 7.5 to 14.5), and OS rate was 92-70-46% at 3-6-12 months, respectively. Disease Control Rate (DCR) was 42.7%. Univariate analysis suggested that the relationship between PFS and baseline fT4 may be modelled with first order polynomial (linear term p=0.06, non-linear term p=0.61) and also suggested a non-linear relationship between PFS and baseline fT3/fT4 (linear term p=0.06, non-linear term p=0.04).When adjusting for major clinical confounding factors (age, ECOG PS, second surgery, MGMT), multivariate analysis identified that baseline fT4 (as a continuous variable) is an independent risk factor for PFS (HR 1.09, 95% CI 1.02 to 1.17; p=0.02). We did not find any statistically significant associations between all baseline thyroid variables with OS and response. Conclusion Our study demonstrated fT4 value to be a predictive biomarker of PFS in recurrent glioblastoma patients treated with regorafenib. No correlation was showed between baseline thyroid function and survival.

Thyroid Rupture Secondary to Blunt Neck Trauma: A Case Report

Aim To discuss the clinical presentation of thyroid rupture following blunt neck trauma and highlight key management principles for the case. Methods A 45-year-old female motorcycle passenger with a pre-existing right thyroid nodule hit her right anterior neck against a bottle during sudden stop and developed painful right neck swelling, odynophagia, and hoarseness. She was seen at the emergency room 5 hours post-injury, awake, cooperative, and ambulatory, without stridor or dyspnea at room air. On examination, she had ecchymoses behind her right tonsillar pillars; her neck was grossly swollen and was tender on palpation without subcutaneous emphysema. Laryngoscopy showed good left vocal cord mobility while the right vocal cord had a visible hemorrhage and limited abduction due to the mass effect of the hematoma seen at the right aryepiglottic area extending toward the right piriform fossa and the right parapharyngeal area. Intact bilateral vocal cord adduction was noted upon phonation. Contrast-enhanced computed tomography revealed hematoma formation in the right thyroid lobe area with extension to the right side of the oropharyngeal region, anterior cervical, parapharyngeal, and retropharyngeal space, confirming the aerodigestive tract narrowing and leftward deviation previously noted. Baseline thyroid function tests were normal. Under general anesthesia, the patient underwent neck exploration where the ruptured right thyroid lobe was resected, and the hematoma was evacuated. Results Postoperatively noted significant improvement in neck swelling, odynophagia, and hoarseness. Transient subclinical hyperthyroidism remained asymptomatic and resolved upon outpatient follow-up. A year after the surgery, the patient had a well-healed cervical scar, complete hematoma resolution, and regained her pre-morbid phonation. Conclusion Thyroid gland rupture should be among the considerations for patients presenting with tender neck swelling, progressive hoarseness, and/or dyspnea following neck trauma. Prompt airway assessment and close monitoring for potential compromise are essential to avoid fatal sequelae of external airway compression. Management varies from close observation to surgical neck exploration and should be personalized depending on the severity of thyroid injury and symptomatology.

Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long‐term follow‐up study

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR=9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4levels (OR=0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4may be a protective factor for thyroid dysfunction.