Quality of Life and Decision regret Risk in Graves' Disease after Radioactive Iodine Therapy：A Prospective Cohort Study

Quality of Life and Decision regret Risk in Graves' Disease after Radioactive Iodine Therapy：A Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Quality of Life and Decision regret Risk in Graves' Disease after Radioactive Iodine Therapy：A Prospective Cohort Study Qian Liu, Xueying Luo, Huan Zhou, Ying Huang, Yuxiao Xia, Lina Liu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8033072/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To identify pre-treatment determinants of hypothyroidism and decision regret (DR) following radioiodine (RAI) therapy in Graves’ disease (GD), and to assess their longitudinal impact on health-related quality of life (QoL). Methods Prospective cohort of 500 GD patients receiving RAI. Machine learning models predicted hypothyroidism (3/6 months) and high DR using clinical indices, socio-economic factors, and ThyPRO-39 QoL scores. Longitudinal QoL was assessed at baseline, 3, and 6 months. Results Unmarried (p 5000 CNY/month: 29.67 ± 6.94 vs. 26.10 ± 7.95; p = 0.018) had significantly higher DR. Longer pre-RAI medication (> 12 months: 30.31 ± 15.96 vs. 27.48 ± 10.42; p = 0.015) increased regret. Hypothyroidism models showed poor discrimination (AUC ≤ 0.59). DR prediction was robust (LR AUC = 0.81), driven by pre-treatment stress (β = 1.32, p < 0.001) and anxiety (β = 0.98, p = 0.003). QoL improved in goiter (p < 0.001) and hypermetabolic symptoms (p < 0.001) at 3 months, while overall QoL (p 0.05). Conclusion Non-clinical factors (marital/employment/income status) and psychological states strongly predict post-RAI regret. Hypothyroidism remains unpredictable, but high DR risk can be accurately identified (AUC = 0.81) for targeted intervention. Persistent cognitive impairment requires clinical attention despite biochemical normalization. Health sciences/Diseases Health sciences/Endocrinology Health sciences/Health care Health sciences/Medical research Graves' disease Radioiodine therapy Hypothyroidism Decision regret Quality of Life Machine learning Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Hyperthyroidism, especially that caused by Graves' disease(GD), is a common endocrine disorder posing significant challenges to patients' physical and mental health( 1 ). Graves' disease leads to excessive thyroid hormone secretion, resulting in hypermetabolism and increased nervous system excitability( 2 ). Patients often experience symptoms such as palpitations, hyperhidrosis, hand tremors, weight loss, and mood swings. Without timely intervention, GD may progress to serious complications, including atrial fibrillation, osteoporosis, and neuropsychiatric manifestations. Furthermore, patients' mental health is severely affected, with frequent psychological problems such as anxiety and depression( 3 ), which significantly reduce their quality of life. Radioactive Iodine Therapy (RAI) is an important GD treatment, using β-ray radiation from iodine-131 to destroy overactive thyroid cells, achieving high biochemical remission rates( 4 ). It utilizes the β-ray radiation effect of radioactive iodine (usually iodine-131) to selectively destroy overactive thyroid cells, thereby reducing thyroid hormone synthesis and secretion( 5 ). It is less invasive than surgery, with few side effects and stable long-term outcomes( 6 ). However, RAI may cause hypothyroidism, dry mouth, or sialadenitis, and its impact on QoL and mental health remains debated.Post-treatment uncertainty, especially regarding hypothyroidism, may induce decision regret (DR), affecting compliance and QoL( 7 ). After RAI treatment, due to the uncertainty of treatment outcomes, especially when hypothyroidism occurs, patients may experience decision-regret emotions. This emotion can increase psychological burden, affect subsequent treatment compliance and effectiveness, and negatively impact overall treatment experience and quality of life( 8 , 9 ). This study aims to comprehensively evaluate the impact of RAI treatment on the quality of life and psychological adaptability of GD, explore the generation mechanism and influencing factors of post-treatment decision-regret emotions, and construct a decision-regret risk assessment model to predict the likelihood of hypothyroidism after RAI treatment. This provides a scientific basis for clinicians to better balance treatment effectiveness and risks, offer personalized psychological support and intervention measures to patients, improve patients' overall treatment experience, enhance treatment effectiveness and patient satisfaction, and promote the development of hyperthyroidism treatment. Materials and Methods Patients The study population consisted of patients with Graves' disease who were treated at the Department of Nuclear Medicine, Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital. General information (name, sex, age, disease duration, contact details) of patients was recorded. Inclusion criteria The inclusion criteria( 10 , 11 ) were strictly based on the diagnostic criteria for diffuse toxic goiter in Internal Medicine: clinical manifestations of diffuse thyroid swelling with hyperthyroidism, including symptoms of hypermetabolism (e.g., excessive sweating, palpitations, increased appetite but weight loss), diffuse enlargement of both thyroid lobes, and exophthalmos in some patients; audible vascular murmurs and palpable thrill at the upper poles of the thyroid gland during physical examination; and laboratory test results consistent with hyperthyroidism, such as elevated free triiodothyronine (FT3) and free thyroxine (FT4), significantly decreased highly sensitive thyroid-stimulating hormone (TSH), and positive thyroid peroxidase antibodies (TPOAb) and/or thyroid-stimulating hormone receptor antibodies (TRAb). Exclusion criteria The exclusion criteria( 12 ) were as follows: patients with hyperthyroid symptoms caused by other diseases, such as Hashimoto's hyperthyroidism, drug-induced hyperthyroidism, subacute thyroiditis, toxic multinodular goiter, autonomous thyroid adenoma, and differentiated thyroid cancer; patients with organic diseases in other systems; and patients with a history of mental illness. By strictly defining the inclusion and exclusion criteria, we ensured the homogeneity of the study population, thereby improving the accuracy and reliability of the study results. Methods Laboratory and Diagnostic Assessments Thyroid Function Analysis Serum thyroid indices FT3, FT4, TSH, and TRAb were quantified by chemiluminescent immunoassay (Siemens Healthineers, Germany); liver function tests and complete blood counts (CBC) were performed on automated platforms (Mindray BS-2000M and Sysmex XN-3000, respectively).Normal reference ranges were defined as: FT3 4.7–7.2pmol/L, FT4 11.61-21.41pmol/L, TSH 0.51-4.94mIU/L, and TRAb < 1.7 IU/L. Hepatic and Hematological Parameters Liver function and complete blood count (CBC) were analyzed from the serum samples using automated biochemistry (Mindray BS-2000M,Shenzhen Mindray Bio-Medical Electronics Co., Ltd., China) and hematology (Sysmex XN-3000,Sysmex Corporation, Kobe, Japan) platforms. Leukocyte counts were interpreted using standard thresholds (3.5–9.5 × 10⁹/L). Thyroid Morphology and Cardiac Evaluation Thyroid nodules were evaluated using a Mindray M9 Ultrasound System (Mindray, Shenzhen, China) equipped with a high-resolution linear probe, and were classified according to the Thyroid Imaging Reporting and Data System (TI-RADS) criteria( 13 ). Thyrotoxic heart disease was diagnosed by 12-lead electrocardiography (BI 12E, Boin Instrument Co., Ltd., Shenzhen, China) according to AHA/ACC criteria( 14 ). Thyroid radioactive iodine uptake Thyroid radioactive iodine uptake (RAIU) ( 5 , 15 )was measured according to standardized nuclear medicine protocols(NM-6110 Thyroid Uptake Meter, Anhui Zhongke Zhongjia Scientific Instrument Co., Ltd., China). Oral ingestion of 131 I-sodium iodide (74-185kBq/2–5 µCi; Beijing Atom High Tech, China) was followed by γ-counting with fixed 4-cm source-to-detector distance. Uptake measurements were acquired at 4 and 24 hours post-ingestion. The RAIU percentage was calculated as: $$\:\text{RAIU}\text{(%)}\text{=}\frac{\text{Neck}\text{}\text{counts}\text{−}\text{T}\text{ℎ}\text{ig}\text{ℎ}\text{counts}\text{}}{\text{Standard}\text{}\text{dose}\text{}\text{counts}}\text{×100}$$ Normal reference ranges were defined as: 5–15% (4 h), 10–30% (24 h). All procedures complied with institutional radiation safety regulations (ALARA principle( 16 )). Psychological assessments Thyroid-Specific Quality of Life: ThyPRO-39 The validated Chinese version of the 39-item Thyroid-Related Patient-Reported Outcome questionnaire (ThyPRO-39)( 17 ) was administered to assess disease-specific quality of life (QoL). This instrument utilizes a 5-point Likert scale (0="not at all" to 4="very much") with total scores ranging from 0 to 156 (higher scores indicating poorer QoL). The scale demonstrated excellent internal consistency in our cohort (Cronbach's α = 0.91). Assessments were performed at:Baseline (pre-treatment),3 months post-treatment,6 months post-treatment. Treatment Decision Regret: Decision Regret Scale (DRS) Regret regarding therapeutic choices was evaluated using the 5-item DRS( 18 ): Items (e.g., "I would make the same choice if I had to do it over again") were scored on a 5-point Likert scale (1 = strongly agree, 5 = strongly disagree). Raw scores were linearly transformed to a 0–100 metric, with scores ≥ 25 indicating clinically significant regret. This assessment was conducted exclusively at 6 months post-intervention. All self-report assessments were conducted in a quiet, private room under the supervision of trained research staff. Recall periods were specified as the preceding four weeks (ThyPRO-39) or since RAI administration (DRS). Statistical Analysis Analyses used R 4.3.1 and SPSS 28.0. Continuous variables: mean ± SD; categorical variables: frequencies/percentages. Longitudinal QoL changes were analyzed via paired t-tests. Linear regression identified DR predictors (β coefficients, 95% CI). Machine learning models (logistic regression, decision tree) with 10-fold cross-validation predicted hypothyroidism and DR, evaluated via AUC, sensitivity, and specificity. p < 0.05 was significant( 19 ), along with sensitivity and specificity metrics.Feature importance was determined using model-specific approaches: SHAP (SHapley Additive exPlanations) values( 20 ) for logistic regression, and the Gini impurity index for decision trees. Results Demographic Characteristics of patients Among the 500 enrolled participants, 338 (67.6%) were female and 162 (32.4%) male,with no significant difference in sex distribution (χ² = 0.68, p = 0.412). The age distribution was highest in the 30–39 years group (126 cases), followed by 50–59 years (129 cases), and lowest in those over 60 years (36 cases). Maritally, 88.6% (443 cases) were married and 11.4% (57 cases) unmarried, with a significant difference (P < 0.001). Educationally, 38.4% (192 cases) had junior high school or below, 41.8% (209 cases) high school/vocational school, and only 0.4% (2 cases) master’s degrees or above (p = 0.048). Occupationally, 46.8% (234 cases) were employees/workers, 29.8% (149 cases) farmers, and 2.0% (10 cases) each unemployed or retired. Monthly income showed 50.4% (252 cases) in the 3000–5000 CNY range, 43.6% (218 cases) ≤ 3000 CNY, and 6.0% (30 cases) > 5000 CNY (p = 0.018). A family history of thyroid disease was reported in 14.6% (73 cases, p = 0.062) ,as shown in Table 1. Clinical History of patients Of the patients, 67.8% (339 cases) had no prior antithyroid drug (ATD) exposure; 25.8% (129 cases) had received ATD for ≤ 12 months, and 6.4% (32 cases) for > 12 months (Jonckheere-Terpstra trend test, p = 0.015). Regarding hyperthyroidism history, 47.2% (236 cases) had no history, 31.6% (158 cases) for > 0–12 months, and 21.2% (106 cases) for > 12 months (p = 0.041). Iodine-131 dose was 90%) and 10 cases (10–30%). The last ATD dose was 0 mg in 68.0% (340 cases), 2.5–10 mg in 22.6% (113 cases), and higher doses in ≤ 7.0% (p = 0.008). Awareness of hypothyroidism was reported in 98.6% (493 cases, p = 0.051), and 97.6% (488 cases) were recommended iodine-131 therapy, with 2.4% (12 cases) not recommended (p < 0.001). Liver function abnormalities occurred in 17.0% (85 cases, p = 0.512), and white blood cell count abnormalities in 6.2% (31 cases, p = 0.003). Thyroid nodules were present in 14.2% (71 cases), and thyroid heart disease in 2.4% (12 cases), with no significant differences (p = 0.538 and p = 0.781, respectively) (Table 2). Baseline Characteristics and Determinants of Decision Regret A comprehensive regression analysis identified key predictors of post-treatment regret. Unmarried patients had 32.5% higher regret scores (36.38 ± 7.92 vs. 27.50 ± 8.55 in married patients; β = 8.88, 95% CI: 5.12–12.64, P 5000 CNY showed significantly higher regret (29.67 ± 6.94) than the ≤ 3000 CNY group (26.10 ± 7.95, P = 0.021). Prolonged antithyroid drug use (> 12 months) correlated with a 14.3% increase in regret (30.31 ± 15.96 vs. 26.52 ± 6.41, P = 0.038). Patients declining iodine-131 therapy had markedly higher regret (55.00 ± 24.68 vs. 26.32 ± 6.38, P < 0.001). Abnormal white blood cell counts (33.06 ± 15.79 vs. 26.61 ± 7.66, P = 0.003) and low thyroid uptake (10–30%: 31.50 ± 24.84 vs. 30–90%: 26.93 ± 7.90, P = 0.051) were also linked to higher regret (Table 1 and 2). Longitudinal Trajectory of Thyroid-Specific Quality of Life Serial paired t-tests assessed temporal changes in disease-specific quality of life to quantify therapeutic benefits. ThyPRO-39 scores improved significantly after RAI therapy at all timepoints. At 3 months, 11 of 12 ThyPRO-39 domains showed significant improvement (all p < 0.001), with the largest gains in fatigue (mean change − 36.0 points; 95% CI − 39.2 to − 32.8), depressive symptoms (− 26.7; 95% CI − 29.8 to − 23.6), and infection susceptibility (− 25.7; 95% CI − 28.6 to − 22.8). The composite score dropped from 38.91 ± 17.10 to 13.83 ± 11.24 (p < 0.001). By 6 months, all domains improved significantly, including the previously unchanged overall QoL (QoL39: 33.60 ± 30.63 → 22.30 ± 24.57; p < 0.001). Continued improvement from 3 to 6 months was seen in goiter symptoms (7.36 ± 9.09 → 6.40 ± 7.02; p < 0.001), hyperthyroid manifestations (18.55 ± 18.28 → 12.43 ± 13.00; p < 0.001), and composite scores (13.83 ± 11.24 → 13.15 ± 10.98; p < 0.001). Notably, cognitive function (Cognition39) showed no improvement between 3 and 6 months (10.77 ± 14.49 vs. 10.77 ± 14.04; p = 1.000) (Table 3 and Fig. 1 ). Predictive Modeling for Hypothyroidism To develop clinical decision-support tools, we built machine learning models with 10-fold cross-validation. Neither logistic regression nor decision-tree algorithms effectively predicted incident hypothyroidism, with AUC values of 0.57 (95% CI 0.51–0.63) at 3 months and 0.59 (95% CI 0.53–0.65) at 6 months; decision-tree models performed no better than random classification (AUC ≤ 0.53). For 3-month hypothyroidism, the top predictors in the decision tree were TRAb levels, patient age, and pre-treatment medication duration, while logistic regression highlighted pre-treatment anxiety, perceived stress, and ThyPRO-39 Cosmetic domain scores. For 6-month hypothyroidism, the decision tree prioritized pre-treatment ocular symptoms, composite QoL score, and hyperthyroidism history duration, whereas logistic regression emphasized baseline ocular manifestations, pre-treatment anxiety, and FT4 levels (Figs. 2 and 3 ). Predictive Modeling for Regret In contrast to hypothyroidism prediction, regret classification models demonstrated significant clinical utility. A logistic-regression model demonstrated good discrimination for high DR (AUC = 0.81; 95% CI 0.75–0.87), with liver-function abnormalities (adjusted OR = 3.21; 95% CI 1.52–6.78; p = 0.002), antithyroid-drug duration > 12 months (adjusted OR = 2.78; 95% CI 1.30–5.93; p = 0.008), and each additional mCi of ¹³¹I (adjusted OR = 1.18 per mCi; 95% CI 1.02–1.37; p = 0.023) as independent predictors in Fig. 4 . Decision tree analysis emphasized baseline depression (Depress39 ≥ 35; OR = 4.05) and low thyroid uptake (< 30%; OR = 3.17) as critical classifiers. Post-hoc analysis confirmed a strong inverse association between regret intensity and QoL recovery: high-regret patients exhibited significantly worse ThyPRO-39 scores at both 3 and 6 months across all domains (*p* < 0.01 vs. low-regret group) in Fig. 4 . Discussion GD, is a common endocrine disorder with a complex pathogenesis( 21 ). It not only involves genetic immunity, immune regulation abnormalities, and environmental factors( 22 ) but is also closely related to psychological stress, falling into the category of psychosomatic diseases( 7 , 23 ). Psychological stress can trigger emotional responses via the limbic system( 24 ), leading to endocrine disorders( 25 , 26 ) and the secretion of large amounts of autoantibodies( 27 ), thereby inducing hyperthyroidism( 28 ). Negative emotions after the onset of the disease can worsen the condition, creating a vicious cycle. Studies both domestically and internationally have indicated that hyperthyroidism patients often suffer from psychological issues such as depression and anxiety( 29 ). They frequently exhibit personality traits like emotional instability, anxiety, irritability, and introversion. RAI is an effective treatment for GD and other types of hyperthyroidism( 30 ). However, the impact of RAI on patients' quality of life and mental health remains controversial. On one hand, RAI may lead to hypothyroidism, affecting patients' quality of life( 31 ). On the other hand, some studies have found that as the condition improves with RAI treatment, patients' anxiety, depression, and other psychological problems significantly decrease( 32 ). This suggests that RAI can rapidly improve psychological issues in the short term, benefiting disease recovery. By integrating clinical parameters with non-clinical metrics—including QoL assessments and DR quantification—we demonstrate that DR, a critical yet understudied patient-centered outcome, is predominantly driven by non-clinical determinants. Unmarried patients reported a 32.5% higher regret score compared to their married counterparts, highlighting the protective role of perceived social support in attenuating post-treatment psychological distress.This observation aligns with Social Baseline Theory, which posits that intimate relationships buffer stress through neurobiological mechanisms facilitating shared emotional processing and resource pooling( 33 , 34 ).Paradoxically, individuals with higher monthly income (> 5,000 CNY) exhibited significantly greater regret, challenging the prevailing assumption that financial security mitigates healthcare-related psychological burden.This inverse income–regret relationship may reflect a discrepancy between treatment expectations and clinical reality: patients with greater financial resources may perceive RAI as a definitive “cure,” thereby underestimating the long-term implications of iatrogenic hypothyroidism.( 35 ). Catastrophic regret levels in patients declining RAI therapy further expose critical deficiencies in shared decision-making processes, suggesting that current informed consent protocols inadequately address psychosocial vulnerabilities even when formally documented. Importantly, regret intensity demonstrated significant variations according to clinical history duration, radioactive iodine uptake patterns, and leukopenia status. These findings compel clinicians managing GD to integrate psychosocial profiling into therapeutic decision-making, providing targeted psychological guidance to mitigate post-treatment dissatisfaction. Longitudinal ThyPRO-39 assessments revealed significant global QoL improvements post-RAI, but exposed dissociated recovery trajectories across symptom domains. Physical manifestations—including fatigue and hypermetabolic symptoms—resolved rapidly, consistent with normalization of sympathetic hyperactivity. Conversely, cognitive dysfunction showed no improvement between 3–6 months, indicating persistent central nervous system dysregulation despite biochemical euthyroidism. This challenges the prevailing paradigm that hyperthyroidism-associated cognitive deficits( 36 ) fully reverse with treatment and warrants investigation into potential neuroendocrine mechanisms. Our predictive modeling yielded fundamentally divergent insights, revealing critical limitations in hypothyroidism prognostication alongside clinically actionable predictors of DR. Methodologically, our psychological assessments employed rigorously validated instruments: The Chinese version of ThyPRO-39( 37 )—developed through standardized forward/backward translation and cognitive debriefing—demonstrates excellent psychometric properties in thyroid populations. Similarly, the DRS has been linguistically and culturally validated in Chinese healthcare contexts, showing strong internal consistency and construct validity against EQ-5D utilities( 38 ). These robust measurement approaches ensure the reliability of our core findings.In our research,hypothyroidism prediction models demonstrated poor discrimination at both 3-month (AUC = 0.57) and 6-month (AUC = 0.59) intervals, likely attributable to their dependence on stochastic biological variables—such as individual follicular cell radiosensitivity and TRAb-mediated autoimmune reactivation—that escape capture in routine clinical data. Future multi-center cohorts incorporating genetic polymorphisms known to modulate RAI responsiveness may enhance predictive performance( 39 ). In striking contrast, DR was accurately forecasted (logistic regression AUC = 0.81) through identifiable modifiable risk factors: prolonged antithyroid drug use > 12 months (OR = 2.78), potentially fostering therapeutic inertia and unrealistic cure expectations, and liver dysfunction (OR = 3.21). Critically, the robust inverse correlation between regret intensity and QoL recovery establishes regret as a clinically meaningful proxy for therapeutic failure transcending conventional biochemical endpoints. These findings mandate three practice transformations: implementation of pre-RAI psychosocial screening using a 4-item checklist (unmarried status, high income, extended ATD use, baseline depression) to trigger targeted cognitive-behavioral interventions. And initiation of computerized cognitive training during the 3–6 month window when physical symptoms stabilize but cognitive deficits persist.We also found integration of our mid-high regret classifier (sensitivity 86%, specificity 79%) into electronic health records for real-time flagging of at-risk patients requiring decision-support consultations. To reduce post-treatment DR, proactively identify high-risk patients via a 4-item pre-RAI psychosocial screening (unmarried status, high income, antithyroid drug use > 12 months, baseline depression/anxiety). These patients should receive pre-emptive psychological support (e.g., cognitive-behavioral therapy) focusing on realistic expectations, hypothyroidism management strategies, and stress reduction.Persistent cognitive dysfunction, despite biochemical euthyroidism, requires attention: clinicians should assess cognition 3–6 months post-RAI and consider interventions like computerized cognitive training.Integrate the validated mid-high regret classifier (86% sensitivity, 79% specificity) into electronic health records to flag at-risk patients for timely decision-support consultations.Refine shared decision-making and informed consent by explicitly addressing psychosocial vulnerabilities, discussing potential regret, and emphasizing lifelong iatrogenic hypothyroidism implications.While providing valuable insights, this study has limitations that should guide future research. Its single-center design and the absence of a non-RAI treatment control group limit the generalizability of the findings. The 6-month follow-up period, although capturing significant early changes, may be insufficient to fully understand the long-term trajectory of QoL and the evolution of DR over time. Future research should prioritize multi-center studies with extended follow-up durations to validate and expand upon these results. Finally, the promising DR prediction model warrants external validation in diverse patient populations and healthcare settings to confirm its robustness and clinical utility beyond the current cohort. Conclusion Managing GD with RAI requires integrating clinical and psychosocial factors. Key pre-RAI risk factors for decision regret (unmarried, high-income, unemployed, prolonged pre-treatment) are identifiable. Hypothyroidism is unpredictable, but high regret risk can be accurately forecasted (AUC = 0.81) via pre-treatment psychological state and clinical history. Proactive screening and targeted intervention for high-risk patients reduce regret and improve long-term QoL. Persistent cognitive dysfunction, despite biochemical normalization, needs clinical attention. This shifts GD management from a purely biochemical focus to a biopsychosocial framework, optimizing patient-centered outcomes. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital (Approval No. KT-2024-014). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This work is supported by sichuan provincial medical youth innovation research project (Q21076), chengdu city technology innovation and research development project (2022-YF05-01418-SN),chengdu medical research project (2024308) and Clinical Scientific Research Fund of Chengdu Medical College(24LHHYFS-06). Author Contribution Y.S. and X.J. conceived and designed the study; Q.L. and X.L wrote the original draft and revised the manuscript critically for intellectual content; H.Z., Y.H., and L.L. organized, curated, and validated the data. All authors critically reviewed the manuscript, approved the final version, and agree to be accountable for all aspects of the work. Acknowledgement We appreciated Dr. Torquil Watt for authorising us to utilise the Chinese version of ThyPRO‐39 questionnaire. For authorising the Chinese version of the DRS scale, kindly acknowledge Dr. Xiaowei Zhang. 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Analysis of psychological status and related factors in hyperthyroidism patients (Shanxi Medical University, 2010). Puja, K. P., Shane, B. J. & Conor, L. Synaptic Mechanisms Regulating Mood State Transitions in Depression. Annu. Rev. Neurosci. ; 45 (0). (2022). Sarah, A. B. & Larry, J. Y. The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives. Biology (Basel) ; 12 (6). (2023). Bence, B. et al. Psychological factors and obesity, not thyroid biomarkers, predict thyroid-dependent quality of life in treated hypothyroidism: a cross-sectional study. BMC Endocr. Disord ; 25 (1). (2025). Mads, L-J., Inge, P., Kaare, C., Laszlo, H. & Thomas Heiberg, B. Is previous hyperthyroidism associated with long-term cognitive dysfunction? A twin study. Clin. Endocrinol. (Oxf) ; 80 (2). (2013). Yue, L. et al. Quality of life and decision regret in patients with late-hypothyroidism after radioiodine treatment for Graves' disease. Clin. Endocrinol. (Oxf) ; 100 (1). (2023). Chen, F. & Cheng, X. J. Reliability and validity of the Chinese version of the Decision Regret Scale in facial cosmetic surgery patients. J. Nurs. (2018). Cuige, L. et al. Expression levels and genetic polymorphisms of interleukin-2 and interleukin-10 as biomarkers of Graves' disease. Exp. Ther. Med. ; 9 (3). (2015). Tables Table 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tab1.docx Tab2.docx TABLE3.docx file.xls Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8033072","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":553870100,"identity":"52f550d5-e04e-4571-8f5b-44da1cf0630d","order_by":0,"name":"Qian Liu","email":"","orcid":"","institution":"the Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Liu","suffix":""},{"id":553870101,"identity":"36148c5a-b99c-4919-8092-823407d4cf93","order_by":1,"name":"Xueying 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1","display":"","copyAsset":false,"role":"figure","size":1243876,"visible":true,"origin":"","legend":"\u003cp\u003eLongitudinal changes in ThyPRO-39 domains and association with decision regret\u003c/p\u003e\n\u003cp\u003e(A) ThyPRO-39 domain scores at 3 months post-RAI ;(B) ThyPRO-39 domain scores at 6 months post-RAI ;(C) Pre-RAI: High-regret group (DRS ≥25) showed universally worse QoL (*p*\u0026lt;0.01).(D) 3 months: Significant QoL gap persisted across all domains.(E) 6 months: Cognitive function remained impaired in high-regret group despite biochemical euthyroidism.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/c496a8ab1d9d089f87e12bb7.jpg"},{"id":97371208,"identity":"26fba060-4e37-4165-bd40-a8c55ea86283","added_by":"auto","created_at":"2025-12-03 16:28:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":713917,"visible":true,"origin":"","legend":"\u003cp\u003eHypothyroidism prediction model at 3 months post-RAI\u003c/p\u003e\n\u003cp\u003e(A) LR feature importance (top 15 predictors): TRAb, age, pre-RAI medication duration;(B) LR ROC curve (AUC = 0.57, 95% CI: 0.51-0.63);(C) DT feature importance: TRAb, age, FT4;(D) DT ROC curve (AUC = 0.53).\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/8e9d3977b843aa0d95605162.jpg"},{"id":97370103,"identity":"85888f45-98b4-49e5-ab9f-96f7dca154a1","added_by":"auto","created_at":"2025-12-03 16:26:45","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":715436,"visible":true,"origin":"","legend":"\u003cp\u003eHypothyroidism prediction model at 6 months post-RAI\u003c/p\u003e\n\u003cp\u003e(A) LR feature importance: Baseline ocular symptoms, anxiety, FT4;(B) LR ROC curve (AUC = 0.59, 95% CI: 0.53-0.65);(C) DT feature importance: Ocular symptoms, composite QoL score, hyperthyroidism duration;(D) DT ROC curve (AUC = 0.50).\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/5a489a2c9d3cc1d20f6f2195.jpg"},{"id":97345749,"identity":"5d16e02b-29b1-4e36-96cf-3cc40ed4a704","added_by":"auto","created_at":"2025-12-03 11:46:05","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":760731,"visible":true,"origin":"","legend":"\u003cp\u003eDecision regret prediction model\u003c/p\u003e\n\u003cp\u003e(A) LR feature importance: Pre-treatment stress (β=1.32), anxiety (β=0.98), RAI dose, abnormal liver function (OR=3.21), ATD duration \u0026gt;12mo (OR=2.78);(B) LR ROC curve (AUC = 0.81, 95% CI: 0.75-0.87);(C) DT feature importance: Baseline depression (Depress39 ≥35), low thyroid uptake (\u0026lt;30%);(D) DT ROC curve (AUC = 0.74).\u003c/p\u003e","description":"","filename":"figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/d13beba738b88e313bfb8285.jpg"},{"id":98622265,"identity":"6759d506-10d7-4830-b926-bd5cd42be159","added_by":"auto","created_at":"2025-12-19 16:50:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4286748,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/e7c55aed-68e4-4243-8286-4aff4accd3d4.pdf"},{"id":97345739,"identity":"252d2e2a-bfd2-4d71-bf4c-c24456e52e95","added_by":"auto","created_at":"2025-12-03 11:46:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15420,"visible":true,"origin":"","legend":"","description":"","filename":"Tab1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/dedcf34aee83c14f3e908d12.docx"},{"id":97370970,"identity":"960e9ad2-4c91-4d07-a876-09b6154feb0b","added_by":"auto","created_at":"2025-12-03 16:28:12","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":15813,"visible":true,"origin":"","legend":"","description":"","filename":"Tab2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/42357da62b7c7b3532aeca60.docx"},{"id":97371311,"identity":"3cebc7bc-9f4c-44cd-8ba1-1829e53ce06f","added_by":"auto","created_at":"2025-12-03 16:28:42","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":15846,"visible":true,"origin":"","legend":"","description":"","filename":"TABLE3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/1558fd6e43d7228302d1cd42.docx"},{"id":97371325,"identity":"be3f54ab-e85a-4db5-993a-dcde9a883a8d","added_by":"auto","created_at":"2025-12-03 16:28:43","extension":"xls","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":285184,"visible":true,"origin":"","legend":"","description":"","filename":"file.xls","url":"https://assets-eu.researchsquare.com/files/rs-8033072/v1/5eb75cc8d380dc9938e28674.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quality of Life and Decision regret Risk in Graves' Disease after Radioactive Iodine Therapy：A Prospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHyperthyroidism, especially that caused by Graves' disease(GD), is a common endocrine disorder posing significant challenges to patients' physical and mental health(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Graves' disease leads to excessive thyroid hormone secretion, resulting in hypermetabolism and increased nervous system excitability(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Patients often experience symptoms such as palpitations, hyperhidrosis, hand tremors, weight loss, and mood swings. Without timely intervention, GD may progress to serious complications, including atrial fibrillation, osteoporosis, and neuropsychiatric manifestations. Furthermore, patients' mental health is severely affected, with frequent psychological problems such as anxiety and depression(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), which significantly reduce their quality of life.\u003c/p\u003e\u003cp\u003eRadioactive Iodine Therapy (RAI) is an important GD treatment, using β-ray radiation from iodine-131 to destroy overactive thyroid cells, achieving high biochemical remission rates(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). It utilizes the β-ray radiation effect of radioactive iodine (usually iodine-131) to selectively destroy overactive thyroid cells, thereby reducing thyroid hormone synthesis and secretion(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is less invasive than surgery, with few side effects and stable long-term outcomes(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, RAI may cause hypothyroidism, dry mouth, or sialadenitis, and its impact on QoL and mental health remains debated.Post-treatment uncertainty, especially regarding hypothyroidism, may induce decision regret (DR), affecting compliance and QoL(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). After RAI treatment, due to the uncertainty of treatment outcomes, especially when hypothyroidism occurs, patients may experience decision-regret emotions. This emotion can increase psychological burden, affect subsequent treatment compliance and effectiveness, and negatively impact overall treatment experience and quality of life(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis study aims to comprehensively evaluate the impact of RAI treatment on the quality of life and psychological adaptability of GD, explore the generation mechanism and influencing factors of post-treatment decision-regret emotions, and construct a decision-regret risk assessment model to predict the likelihood of hypothyroidism after RAI treatment. This provides a scientific basis for clinicians to better balance treatment effectiveness and risks, offer personalized psychological support and intervention measures to patients, improve patients' overall treatment experience, enhance treatment effectiveness and patient satisfaction, and promote the development of hyperthyroidism treatment.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eThe study population consisted of patients with Graves' disease who were treated at the Department of Nuclear Medicine, Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital. General information (name, sex, age, disease duration, contact details) of patients was recorded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe inclusion criteria(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) were strictly based on the diagnostic criteria for diffuse toxic goiter in Internal Medicine: clinical manifestations of diffuse thyroid swelling with hyperthyroidism, including symptoms of hypermetabolism (e.g., excessive sweating, palpitations, increased appetite but weight loss), diffuse enlargement of both thyroid lobes, and exophthalmos in some patients; audible vascular murmurs and palpable thrill at the upper poles of the thyroid gland during physical examination; and laboratory test results consistent with hyperthyroidism, such as elevated free triiodothyronine (FT3) and free thyroxine (FT4), significantly decreased highly sensitive thyroid-stimulating hormone (TSH), and positive thyroid peroxidase antibodies (TPOAb) and/or thyroid-stimulating hormone receptor antibodies (TRAb).\u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe exclusion criteria(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) were as follows: patients with hyperthyroid symptoms caused by other diseases, such as Hashimoto's hyperthyroidism, drug-induced hyperthyroidism, subacute thyroiditis, toxic multinodular goiter, autonomous thyroid adenoma, and differentiated thyroid cancer; patients with organic diseases in other systems; and patients with a history of mental illness. By strictly defining the inclusion and exclusion criteria, we ensured the homogeneity of the study population, thereby improving the accuracy and reliability of the study results.\u003c/p\u003e\n\u003ch3\u003eMethods\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory and Diagnostic Assessments\u003c/h2\u003e\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\u003ch2\u003eThyroid Function Analysis\u003c/h2\u003e\u003cp\u003eSerum thyroid indices FT3, FT4, TSH, and TRAb were quantified by chemiluminescent immunoassay (Siemens Healthineers, Germany); liver function tests and complete blood counts (CBC) were performed on automated platforms (Mindray BS-2000M and Sysmex XN-3000, respectively).Normal reference ranges were defined as: FT3 4.7\u0026ndash;7.2pmol/L, FT4 11.61-21.41pmol/L, TSH 0.51-4.94mIU/L, and TRAb\u0026thinsp;\u0026lt;\u0026thinsp;1.7 IU/L.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eHepatic and Hematological Parameters\u003c/h3\u003e\n\u003cp\u003eLiver function and complete blood count (CBC) were analyzed from the serum samples using automated biochemistry (Mindray BS-2000M,Shenzhen Mindray Bio-Medical Electronics Co., Ltd., China) and hematology (Sysmex XN-3000,Sysmex Corporation, Kobe, Japan) platforms. Leukocyte counts were interpreted using standard thresholds (3.5\u0026ndash;9.5 \u0026times; 10⁹/L).\u003c/p\u003e\n\u003ch3\u003eThyroid Morphology and Cardiac Evaluation\u003c/h3\u003e\n\u003cp\u003eThyroid nodules were evaluated using a Mindray M9 Ultrasound System (Mindray, Shenzhen, China) equipped with a high-resolution linear probe, and were classified according to the Thyroid Imaging Reporting and Data System (TI-RADS) criteria(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThyrotoxic heart disease was diagnosed by 12-lead electrocardiography (BI 12E, Boin Instrument Co., Ltd., Shenzhen, China) according to AHA/ACC criteria(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eThyroid radioactive iodine uptake\u003c/h2\u003e\u003cp\u003eThyroid radioactive iodine uptake (RAIU) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)was measured according to standardized nuclear medicine protocols(NM-6110 Thyroid Uptake Meter, Anhui Zhongke Zhongjia Scientific Instrument Co., Ltd., China). Oral ingestion of \u003csup\u003e131\u003c/sup\u003eI-sodium iodide (74-185kBq/2\u0026ndash;5 \u0026micro;Ci; Beijing Atom High Tech, China) was followed by γ-counting with fixed 4-cm source-to-detector distance. Uptake measurements were acquired at 4 and 24 hours post-ingestion. The RAIU percentage was calculated as:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\text{RAIU}\\text{(%)}\\text{=}\\frac{\\text{Neck}\\text{}\\text{counts}\\text{\u0026minus;}\\text{T}\\text{ℎ}\\text{ig}\\text{ℎ}\\text{counts}\\text{}}{\\text{Standard}\\text{}\\text{dose}\\text{}\\text{counts}}\\text{\u0026times;100}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNormal reference ranges were defined as: 5\u0026ndash;15% (4 h), 10\u0026ndash;30% (24 h). All procedures complied with institutional radiation safety regulations (ALARA principle(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePsychological assessments\u003c/h2\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003eThyroid-Specific Quality of Life: ThyPRO-39\u003c/h2\u003e\u003cp\u003eThe validated Chinese version of the 39-item Thyroid-Related Patient-Reported Outcome questionnaire (ThyPRO-39)(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) was administered to assess disease-specific quality of life (QoL). This instrument utilizes a 5-point Likert scale (0=\"not at all\" to 4=\"very much\") with total scores ranging from 0 to 156 (higher scores indicating poorer QoL). The scale demonstrated excellent internal consistency in our cohort (Cronbach's α\u0026thinsp;=\u0026thinsp;0.91). Assessments were performed at:Baseline (pre-treatment),3 months post-treatment,6 months post-treatment.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eTreatment Decision Regret: Decision Regret Scale (DRS)\u003c/h2\u003e\u003cp\u003eRegret regarding therapeutic choices was evaluated using the 5-item DRS(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e): Items (e.g., \"I would make the same choice if I had to do it over again\") were scored on a 5-point Likert scale (1\u0026thinsp;=\u0026thinsp;strongly agree, 5\u0026thinsp;=\u0026thinsp;strongly disagree). Raw scores were linearly transformed to a 0\u0026ndash;100 metric, with scores\u0026thinsp;\u0026ge;\u0026thinsp;25 indicating clinically significant regret. This assessment was conducted exclusively at 6 months post-intervention.\u003c/p\u003e\u003cp\u003eAll self-report assessments were conducted in a quiet, private room under the supervision of trained research staff. Recall periods were specified as the preceding four weeks (ThyPRO-39) or since RAI administration (DRS).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAnalyses used R 4.3.1 and SPSS 28.0. Continuous variables: mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD; categorical variables: frequencies/percentages. Longitudinal QoL changes were analyzed via paired t-tests. Linear regression identified DR predictors (β coefficients, 95% CI). Machine learning models (logistic regression, decision tree) with 10-fold cross-validation predicted hypothyroidism and DR, evaluated via AUC, sensitivity, and specificity. p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was significant(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), along with sensitivity and specificity metrics.Feature importance was determined using model-specific approaches: SHAP (SHapley Additive exPlanations) values(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) for logistic regression, and the Gini impurity index for decision trees.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eDemographic Characteristics of patients\u003c/h2\u003e\u003cp\u003eAmong the 500 enrolled participants, 338 (67.6%) were female and 162 (32.4%) male,with no significant difference in sex distribution (χ\u0026sup2; = 0.68, p\u0026thinsp;=\u0026thinsp;0.412). The age distribution was highest in the 30\u0026ndash;39 years group (126 cases), followed by 50\u0026ndash;59 years (129 cases), and lowest in those over 60 years (36 cases).\u003c/p\u003e\u003cp\u003eMaritally, 88.6% (443 cases) were married and 11.4% (57 cases) unmarried, with a significant difference (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eEducationally, 38.4% (192 cases) had junior high school or below, 41.8% (209 cases) high school/vocational school, and only 0.4% (2 cases) master\u0026rsquo;s degrees or above (p\u0026thinsp;=\u0026thinsp;0.048).\u003c/p\u003e\u003cp\u003eOccupationally, 46.8% (234 cases) were employees/workers, 29.8% (149 cases) farmers, and 2.0% (10 cases) each unemployed or retired.\u003c/p\u003e\u003cp\u003eMonthly income showed 50.4% (252 cases) in the 3000\u0026ndash;5000 CNY range, 43.6% (218 cases)\u0026thinsp;\u0026le;\u0026thinsp;3000 CNY, and 6.0% (30 cases)\u0026thinsp;\u0026gt;\u0026thinsp;5000 CNY (p\u0026thinsp;=\u0026thinsp;0.018). A family history of thyroid disease was reported in 14.6% (73 cases, p\u0026thinsp;=\u0026thinsp;0.062) ,as shown in Table\u0026nbsp;1.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eClinical History of patients\u003c/h2\u003e\u003cp\u003eOf the patients, 67.8% (339 cases) had no prior antithyroid drug (ATD) exposure; 25.8% (129 cases) had received ATD for \u0026le;\u0026thinsp;12 months, and 6.4% (32 cases) for \u0026gt;\u0026thinsp;12 months (Jonckheere-Terpstra trend test, p\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e\u003cp\u003eRegarding hyperthyroidism history, 47.2% (236 cases) had no history, 31.6% (158 cases) for \u0026gt;\u0026thinsp;0\u0026ndash;12 months, and 21.2% (106 cases) for \u0026gt;\u0026thinsp;12 months (p\u0026thinsp;=\u0026thinsp;0.041).\u003c/p\u003e\u003cp\u003eIodine-131 dose was \u0026lt;\u0026thinsp;15 mCi in 82.8% (414 cases) and 15\u0026ndash;30 mCi in 17.2% (86 cases). Thyroid uptake was 30\u0026ndash;90% in 97.6% (488 cases), with only 2 cases (\u0026gt;\u0026thinsp;90%) and 10 cases (10\u0026ndash;30%).\u003c/p\u003e\u003cp\u003eThe last ATD dose was 0 mg in 68.0% (340 cases), 2.5\u0026ndash;10 mg in 22.6% (113 cases), and higher doses in \u0026le;\u0026thinsp;7.0% (p\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e\u003cp\u003eAwareness of hypothyroidism was reported in 98.6% (493 cases, p\u0026thinsp;=\u0026thinsp;0.051), and 97.6% (488 cases) were recommended iodine-131 therapy, with 2.4% (12 cases) not recommended (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eLiver function abnormalities occurred in 17.0% (85 cases, p\u0026thinsp;=\u0026thinsp;0.512), and white blood cell count abnormalities in 6.2% (31 cases, p\u0026thinsp;=\u0026thinsp;0.003). Thyroid nodules were present in 14.2% (71 cases), and thyroid heart disease in 2.4% (12 cases), with no significant differences (p\u0026thinsp;=\u0026thinsp;0.538 and p\u0026thinsp;=\u0026thinsp;0.781, respectively) (Table\u0026nbsp;2).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eBaseline Characteristics and Determinants of Decision Regret\u003c/h2\u003e\u003cp\u003eA comprehensive regression analysis identified key predictors of post-treatment regret. Unmarried patients had 32.5% higher regret scores (36.38\u0026thinsp;\u0026plusmn;\u0026thinsp;7.92 vs. 27.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.55 in married patients; β\u0026thinsp;=\u0026thinsp;8.88, 95% CI: 5.12\u0026ndash;12.64, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Those with monthly income\u0026thinsp;\u0026gt;\u0026thinsp;5000 CNY showed significantly higher regret (29.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.94) than the \u0026le;\u0026thinsp;3000 CNY group (26.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.95, P\u0026thinsp;=\u0026thinsp;0.021).\u003c/p\u003e\u003cp\u003eProlonged antithyroid drug use (\u0026gt;\u0026thinsp;12 months) correlated with a 14.3% increase in regret (30.31\u0026thinsp;\u0026plusmn;\u0026thinsp;15.96 vs. 26.52\u0026thinsp;\u0026plusmn;\u0026thinsp;6.41, P\u0026thinsp;=\u0026thinsp;0.038). Patients declining iodine-131 therapy had markedly higher regret (55.00\u0026thinsp;\u0026plusmn;\u0026thinsp;24.68 vs. 26.32\u0026thinsp;\u0026plusmn;\u0026thinsp;6.38, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eAbnormal white blood cell counts (33.06\u0026thinsp;\u0026plusmn;\u0026thinsp;15.79 vs. 26.61\u0026thinsp;\u0026plusmn;\u0026thinsp;7.66, P\u0026thinsp;=\u0026thinsp;0.003) and low thyroid uptake (10\u0026ndash;30%: 31.50\u0026thinsp;\u0026plusmn;\u0026thinsp;24.84 vs. 30\u0026ndash;90%: 26.93\u0026thinsp;\u0026plusmn;\u0026thinsp;7.90, P\u0026thinsp;=\u0026thinsp;0.051) were also linked to higher regret (Table\u0026nbsp;1 and 2).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eLongitudinal Trajectory of Thyroid-Specific Quality of Life\u003c/h2\u003e\u003cp\u003eSerial paired t-tests assessed temporal changes in disease-specific quality of life to quantify therapeutic benefits. ThyPRO-39 scores improved significantly after RAI therapy at all timepoints. At 3 months, 11 of 12 ThyPRO-39 domains showed significant improvement (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with the largest gains in fatigue (mean change \u0026minus;\u0026thinsp;36.0 points; 95% CI \u0026minus;\u0026thinsp;39.2 to \u0026minus;\u0026thinsp;32.8), depressive symptoms (\u0026minus;\u0026thinsp;26.7; 95% CI \u0026minus;\u0026thinsp;29.8 to \u0026minus;\u0026thinsp;23.6), and infection susceptibility (\u0026minus;\u0026thinsp;25.7; 95% CI \u0026minus;\u0026thinsp;28.6 to \u0026minus;\u0026thinsp;22.8). The composite score dropped from 38.91\u0026thinsp;\u0026plusmn;\u0026thinsp;17.10 to 13.83\u0026thinsp;\u0026plusmn;\u0026thinsp;11.24 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eBy 6 months, all domains improved significantly, including the previously unchanged overall QoL (QoL39: 33.60\u0026thinsp;\u0026plusmn;\u0026thinsp;30.63 \u0026rarr; 22.30\u0026thinsp;\u0026plusmn;\u0026thinsp;24.57; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Continued improvement from 3 to 6 months was seen in goiter symptoms (7.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.09 \u0026rarr; 6.40\u0026thinsp;\u0026plusmn;\u0026thinsp;7.02; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hyperthyroid manifestations (18.55\u0026thinsp;\u0026plusmn;\u0026thinsp;18.28 \u0026rarr; 12.43\u0026thinsp;\u0026plusmn;\u0026thinsp;13.00; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and composite scores (13.83\u0026thinsp;\u0026plusmn;\u0026thinsp;11.24 \u0026rarr; 13.15\u0026thinsp;\u0026plusmn;\u0026thinsp;10.98; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Notably, cognitive function (Cognition39) showed no improvement between 3 and 6 months (10.77\u0026thinsp;\u0026plusmn;\u0026thinsp;14.49 vs. 10.77\u0026thinsp;\u0026plusmn;\u0026thinsp;14.04; p\u0026thinsp;=\u0026thinsp;1.000) (Table\u0026nbsp;3 and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003ePredictive Modeling for Hypothyroidism\u003c/h2\u003e\u003cp\u003eTo develop clinical decision-support tools, we built machine learning models with 10-fold cross-validation. Neither logistic regression nor decision-tree algorithms effectively predicted incident hypothyroidism, with AUC values of 0.57 (95% CI 0.51\u0026ndash;0.63) at 3 months and 0.59 (95% CI 0.53\u0026ndash;0.65) at 6 months; decision-tree models performed no better than random classification (AUC\u0026thinsp;\u0026le;\u0026thinsp;0.53).\u003c/p\u003e\u003cp\u003eFor 3-month hypothyroidism, the top predictors in the decision tree were TRAb levels, patient age, and pre-treatment medication duration, while logistic regression highlighted pre-treatment anxiety, perceived stress, and ThyPRO-39 Cosmetic domain scores.\u003c/p\u003e\u003cp\u003eFor 6-month hypothyroidism, the decision tree prioritized pre-treatment ocular symptoms, composite QoL score, and hyperthyroidism history duration, whereas logistic regression emphasized baseline ocular manifestations, pre-treatment anxiety, and FT4 levels (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003ePredictive Modeling for Regret\u003c/h2\u003e\u003cp\u003eIn contrast to hypothyroidism prediction, regret classification models demonstrated significant clinical utility. A logistic-regression model demonstrated good discrimination for high DR (AUC\u0026thinsp;=\u0026thinsp;0.81; 95% CI 0.75\u0026ndash;0.87), with liver-function abnormalities (adjusted OR\u0026thinsp;=\u0026thinsp;3.21; 95% CI 1.52\u0026ndash;6.78; p\u0026thinsp;=\u0026thinsp;0.002), antithyroid-drug duration\u0026thinsp;\u0026gt;\u0026thinsp;12 months (adjusted OR\u0026thinsp;=\u0026thinsp;2.78; 95% CI 1.30\u0026ndash;5.93; p\u0026thinsp;=\u0026thinsp;0.008), and each additional mCi of \u0026sup1;\u0026sup3;\u0026sup1;I (adjusted OR\u0026thinsp;=\u0026thinsp;1.18 per mCi; 95% CI 1.02\u0026ndash;1.37; p\u0026thinsp;=\u0026thinsp;0.023) as independent predictors in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Decision tree analysis emphasized baseline depression (Depress39\u0026thinsp;\u0026ge;\u0026thinsp;35; OR\u0026thinsp;=\u0026thinsp;4.05) and low thyroid uptake (\u0026lt;\u0026thinsp;30%; OR\u0026thinsp;=\u0026thinsp;3.17) as critical classifiers. Post-hoc analysis confirmed a strong inverse association between regret intensity and QoL recovery: high-regret patients exhibited significantly worse ThyPRO-39 scores at both 3 and 6 months across all domains (*p* \u0026lt; 0.01 vs. low-regret group) in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e .\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGD, is a common endocrine disorder with a complex pathogenesis(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). It not only involves genetic immunity, immune regulation abnormalities, and environmental factors(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) but is also closely related to psychological stress, falling into the category of psychosomatic diseases(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Psychological stress can trigger emotional responses via the limbic system(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), leading to endocrine disorders(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) and the secretion of large amounts of autoantibodies(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), thereby inducing hyperthyroidism(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Negative emotions after the onset of the disease can worsen the condition, creating a vicious cycle. Studies both domestically and internationally have indicated that hyperthyroidism patients often suffer from psychological issues such as depression and anxiety(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). They frequently exhibit personality traits like emotional instability, anxiety, irritability, and introversion.\u003c/p\u003e\u003cp\u003eRAI is an effective treatment for GD and other types of hyperthyroidism(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). However, the impact of RAI on patients' quality of life and mental health remains controversial. On one hand, RAI may lead to hypothyroidism, affecting patients' quality of life(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). On the other hand, some studies have found that as the condition improves with RAI treatment, patients' anxiety, depression, and other psychological problems significantly decrease(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). This suggests that RAI can rapidly improve psychological issues in the short term, benefiting disease recovery.\u003c/p\u003e\u003cp\u003eBy integrating clinical parameters with non-clinical metrics\u0026mdash;including QoL assessments and DR quantification\u0026mdash;we demonstrate that DR, a critical yet understudied patient-centered outcome, is predominantly driven by non-clinical determinants. Unmarried patients reported a 32.5% higher regret score compared to their married counterparts, highlighting the protective role of perceived social support in attenuating post-treatment psychological distress.This observation aligns with Social Baseline Theory, which posits that intimate relationships buffer stress through neurobiological mechanisms facilitating shared emotional processing and resource pooling(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).Paradoxically, individuals with higher monthly income (\u0026gt;\u0026thinsp;5,000 CNY) exhibited significantly greater regret, challenging the prevailing assumption that financial security mitigates healthcare-related psychological burden.This inverse income\u0026ndash;regret relationship may reflect a discrepancy between treatment expectations and clinical reality: patients with greater financial resources may perceive RAI as a definitive \u0026ldquo;cure,\u0026rdquo; thereby underestimating the long-term implications of iatrogenic hypothyroidism.(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Catastrophic regret levels in patients declining RAI therapy further expose critical deficiencies in shared decision-making processes, suggesting that current informed consent protocols inadequately address psychosocial vulnerabilities even when formally documented. Importantly, regret intensity demonstrated significant variations according to clinical history duration, radioactive iodine uptake patterns, and leukopenia status. These findings compel clinicians managing GD to integrate psychosocial profiling into therapeutic decision-making, providing targeted psychological guidance to mitigate post-treatment dissatisfaction.\u003c/p\u003e\u003cp\u003eLongitudinal ThyPRO-39 assessments revealed significant global QoL improvements post-RAI, but exposed dissociated recovery trajectories across symptom domains. Physical manifestations\u0026mdash;including fatigue and hypermetabolic symptoms\u0026mdash;resolved rapidly, consistent with normalization of sympathetic hyperactivity. Conversely, cognitive dysfunction showed no improvement between 3\u0026ndash;6 months, indicating persistent central nervous system dysregulation despite biochemical euthyroidism. This challenges the prevailing paradigm that hyperthyroidism-associated cognitive deficits(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) fully reverse with treatment and warrants investigation into potential neuroendocrine mechanisms.\u003c/p\u003e\u003cp\u003eOur predictive modeling yielded fundamentally divergent insights, revealing critical limitations in hypothyroidism prognostication alongside clinically actionable predictors of DR. Methodologically, our psychological assessments employed rigorously validated instruments: The Chinese version of ThyPRO-39(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e)\u0026mdash;developed through standardized forward/backward translation and cognitive debriefing\u0026mdash;demonstrates excellent psychometric properties in thyroid populations. Similarly, the DRS has been linguistically and culturally validated in Chinese healthcare contexts, showing strong internal consistency and construct validity against EQ-5D utilities(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). These robust measurement approaches ensure the reliability of our core findings.In our research,hypothyroidism prediction models demonstrated poor discrimination at both 3-month (AUC\u0026thinsp;=\u0026thinsp;0.57) and 6-month (AUC\u0026thinsp;=\u0026thinsp;0.59) intervals, likely attributable to their dependence on stochastic biological variables\u0026mdash;such as individual follicular cell radiosensitivity and TRAb-mediated autoimmune reactivation\u0026mdash;that escape capture in routine clinical data. Future multi-center cohorts incorporating genetic polymorphisms known to modulate RAI responsiveness may enhance predictive performance(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). In striking contrast, DR was accurately forecasted (logistic regression AUC\u0026thinsp;=\u0026thinsp;0.81) through identifiable modifiable risk factors: prolonged antithyroid drug use\u0026thinsp;\u0026gt;\u0026thinsp;12 months (OR\u0026thinsp;=\u0026thinsp;2.78), potentially fostering therapeutic inertia and unrealistic cure expectations, and liver dysfunction (OR\u0026thinsp;=\u0026thinsp;3.21). Critically, the robust inverse correlation between regret intensity and QoL recovery establishes regret as a clinically meaningful proxy for therapeutic failure transcending conventional biochemical endpoints. These findings mandate three practice transformations: implementation of pre-RAI psychosocial screening using a 4-item checklist (unmarried status, high income, extended ATD use, baseline depression) to trigger targeted cognitive-behavioral interventions. And initiation of computerized cognitive training during the 3\u0026ndash;6 month window when physical symptoms stabilize but cognitive deficits persist.We also found integration of our mid-high regret classifier (sensitivity 86%, specificity 79%) into electronic health records for real-time flagging of at-risk patients requiring decision-support consultations.\u003c/p\u003e\u003cp\u003eTo reduce post-treatment DR, proactively identify high-risk patients via a 4-item pre-RAI psychosocial screening (unmarried status, high income, antithyroid drug use\u0026thinsp;\u0026gt;\u0026thinsp;12 months, baseline depression/anxiety). These patients should receive pre-emptive psychological support (e.g., cognitive-behavioral therapy) focusing on realistic expectations, hypothyroidism management strategies, and stress reduction.Persistent cognitive dysfunction, despite biochemical euthyroidism, requires attention: clinicians should assess cognition 3\u0026ndash;6 months post-RAI and consider interventions like computerized cognitive training.Integrate the validated mid-high regret classifier (86% sensitivity, 79% specificity) into electronic health records to flag at-risk patients for timely decision-support consultations.Refine shared decision-making and informed consent by explicitly addressing psychosocial vulnerabilities, discussing potential regret, and emphasizing lifelong iatrogenic hypothyroidism implications.While providing valuable insights, this study has limitations that should guide future research. Its single-center design and the absence of a non-RAI treatment control group limit the generalizability of the findings. The 6-month follow-up period, although capturing significant early changes, may be insufficient to fully understand the long-term trajectory of QoL and the evolution of DR over time. Future research should prioritize multi-center studies with extended follow-up durations to validate and expand upon these results. Finally, the promising DR prediction model warrants external validation in diverse patient populations and healthcare settings to confirm its robustness and clinical utility beyond the current cohort.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eManaging GD with RAI requires integrating clinical and psychosocial factors. Key pre-RAI risk factors for decision regret (unmarried, high-income, unemployed, prolonged pre-treatment) are identifiable. Hypothyroidism is unpredictable, but high regret risk can be accurately forecasted (AUC\u0026thinsp;=\u0026thinsp;0.81) via pre-treatment psychological state and clinical history. Proactive screening and targeted intervention for high-risk patients reduce regret and improve long-term QoL. Persistent cognitive dysfunction, despite biochemical normalization, needs clinical attention. This shifts GD management from a purely biochemical focus to a biopsychosocial framework, optimizing patient-centered outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\u003cp\u003e This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital (Approval No. KT-2024-014).\u003c/p\u003e\u003ch2\u003eConsent for publication\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work is supported by sichuan provincial medical youth innovation research project (Q21076), chengdu city technology innovation and research development project (2022-YF05-01418-SN),chengdu medical research project (2024308) and Clinical Scientific Research Fund of Chengdu Medical College(24LHHYFS-06).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eY.S. and X.J. conceived and designed the study; Q.L. and X.L wrote the original draft and revised the manuscript critically for intellectual content; H.Z., Y.H., and L.L. organized, curated, and validated the data. All authors critically reviewed the manuscript, approved the final version, and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe appreciated Dr. Torquil Watt for authorising us to utilise the Chinese version of ThyPRO‐39 questionnaire. For authorising the Chinese version of the DRS scale, kindly acknowledge Dr. Xiaowei Zhang.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee, S. Y., Pearce, E. N. \u0026amp; Hyperthyroidism A Review. \u003cem\u003eJAMA: J. Am. Med. Association\u003c/em\u003e ;\u003cb\u003e330\u003c/b\u003e(15). (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDanielle, D. \u0026amp; Semhar, Z. T. 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(2015).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Graves' disease, Radioiodine therapy, Hypothyroidism, Decision regret, Quality of Life, Machine learning","lastPublishedDoi":"10.21203/rs.3.rs-8033072/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8033072/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo identify pre-treatment determinants of hypothyroidism and decision regret (DR) following radioiodine (RAI) therapy in Graves\u0026rsquo; disease (GD), and to assess their longitudinal impact on health-related quality of life (QoL).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eProspective cohort of 500 GD patients receiving RAI. Machine learning models predicted hypothyroidism (3/6 months) and high DR using clinical indices, socio-economic factors, and ThyPRO-39 QoL scores. Longitudinal QoL was assessed at baseline, 3, and 6 months.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eUnmarried (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), unemployed (35.50\u0026thinsp;\u0026plusmn;\u0026thinsp;23.15 vs. 27.01\u0026thinsp;\u0026plusmn;\u0026thinsp;6.95; p\u0026thinsp;=\u0026thinsp;0.032), and higher income patients (\u0026gt;\u0026thinsp;5000 CNY/month: 29.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.94 vs. 26.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.95; p\u0026thinsp;=\u0026thinsp;0.018) had significantly higher DR. Longer pre-RAI medication (\u0026gt;\u0026thinsp;12 months: 30.31\u0026thinsp;\u0026plusmn;\u0026thinsp;15.96 vs. 27.48\u0026thinsp;\u0026plusmn;\u0026thinsp;10.42; p\u0026thinsp;=\u0026thinsp;0.015) increased regret. Hypothyroidism models showed poor discrimination (AUC\u0026thinsp;\u0026le;\u0026thinsp;0.59). DR prediction was robust (LR AUC\u0026thinsp;=\u0026thinsp;0.81), driven by pre-treatment stress (β\u0026thinsp;=\u0026thinsp;1.32, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and anxiety (β\u0026thinsp;=\u0026thinsp;0.98, p\u0026thinsp;=\u0026thinsp;0.003). QoL improved in goiter (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and hypermetabolic symptoms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at 3 months, while overall QoL (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and depression (p\u0026thinsp;=\u0026thinsp;0.006) improved by 6 months. Cognitive deficits persisted beyond 3 months (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eNon-clinical factors (marital/employment/income status) and psychological states strongly predict post-RAI regret. Hypothyroidism remains unpredictable, but high DR risk can be accurately identified (AUC\u0026thinsp;=\u0026thinsp;0.81) for targeted intervention. Persistent cognitive impairment requires clinical attention despite biochemical normalization.\u003c/p\u003e","manuscriptTitle":"Quality of Life and Decision regret Risk in Graves' Disease after Radioactive Iodine Therapy：A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-03 11:46:00","doi":"10.21203/rs.3.rs-8033072/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"70ecb055-642f-42da-a4e3-3e7c9f4c4291","owner":[],"postedDate":"December 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58935387,"name":"Health sciences/Diseases"},{"id":58935388,"name":"Health sciences/Endocrinology"},{"id":58935389,"name":"Health sciences/Health care"},{"id":58935390,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-14T06:23:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-03 11:46:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8033072","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8033072","identity":"rs-8033072","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}