Thyroid最新文献

{"title":"Long-Term Results of External Beam Radiation Therapy with or Without Concurrent Chemotherapy in Differentiated Thyroid Cancer.","authors":"Justin Choi, Eric Sherman, Edward Christopher Dee, Teeradon Treechairusame, Kaveh Zakeri, Jung Julie Kang, Yao Yu, Linda Chen, Achraf Shamseddine, Sean M McBride, Nadeem Riaz, Alan L Ho, R Michael Tuttle, James Fagin, Mona Sabra, Jennifer Cracchiolo, Ashok Shaha, Richard J Wong, Ronald Ghossein, Nora Katabi, Nancy Y Lee","doi":"10.1089/thy.2025.0052","DOIUrl":"10.1089/thy.2025.0052","url":null,"abstract":"<p><p><b><i>Background:</i></b> A rare group of patients with differentiated thyroid cancers (DTCs) will have gross residual disease or recurrence following the standard primary therapies of surgical resection and radioactive iodine. In these patients with advanced DTC no longer amenable to further surgery, systemic, or radioactive iodine therapies, external beam radiation therapy (RT) is considered. Whether to add concurrent chemotherapy (CRT) to radiation for patients with advanced DTC remains unclear. We review the long-term follow-up of the largest single-institution experience on the use of RT alone versus CRT in advanced DTC. <b><i>Methods:</i></b> From 1989 to 2023, 327 patients with recurrent, gross residual, or unresected DTC were treated with RT alone or CRT. Patients with incomplete resection and/or unfavorable histology were preferentially treated with CRT. For this retrospective cohort study, locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan-Meier method. <b><i>Results:</i></b> CRT patients (<i>n</i> = 153) were 46% female and 61.6 ± 11.7 years old versus RT alone (<i>n</i> = 174) were 48% female and 66.8 ± 12.6 years old. Overall median follow-up was 109.7 months [confidence interval 100.3-123.5 months]. There were no differences in 4- and 10-year LRC, DMFS, or OS rates between groups (4-year LRC 89.0% RT alone vs. 86.6% CRT, <i>p</i> = 0.76; 4-year DMFS: 64.2% RT alone vs. 54.5% CRT, <i>p</i> = 0.08; 4-year OS: 58.5% RT alone vs. 56.9% CRT, <i>p</i> = 0.28). Worse grade 3+ acute dermatitis was reported with CRT (29% CRT vs. 10% RT alone, <i>p</i> < 0.0001). Eight patients developed a tracheoesophageal fistula (TEF), six of whom received CRT followed by tyrosine kinase inhibitor (TKI) therapy. TEF developed at a median of 7.3 months (range = 0.5-17.0 months) after TKI initiation. There were no differences in other acute toxicities, any late toxicities, rates of tracheostomy tube, percutaneous endoscopic gastrostomy (PEG) tube within 60 days of RT, or PEG tube persistence past one year. <b><i>Conclusion:</i></b> CRT did not demonstrate any benefit over RT alone in this retrospective study, although patients treated with CRT had worse disease. Late toxicities were similar, aside from greater TEF development after TKI therapy in CRT patients. Further research is necessary to elucidate who may benefit from CRT.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"35 6","pages":"633-641"},"PeriodicalIF":6.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> \"High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis\" by Fung et al.","authors":"Kennichi Kakudo, Andrey Bychkov, Jen-Fan Hang, Mitsuyoshi Hirokawa, Somboon Keelawat, Zhiyan Liu, Radhika Srinivasan, Chan Kwon Jung","doi":"10.1089/thy.2025.0072","DOIUrl":"10.1089/thy.2025.0072","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"595-596"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment Among Cytologically Indeterminate Thyroid Nodules.","authors":"Jiahui Wu, Paul Stewardson, Markus Eszlinger, Moosa Khalil, Sana Ghaznavi, Erik Nohr, Adrian Box, Ralf Paschke","doi":"10.1089/thy.2024.0481","DOIUrl":"10.1089/thy.2024.0481","url":null,"abstract":"<p><p><b><i>Background:</i></b> The introduction of molecular testing (MT) of cytologically indeterminate thyroid nodules (ITNs) alone has not impacted thyroidectomy rates. Due to this, we evaluated the incremental diagnostic value of various clinical variables in addition to MT results, in predicting the risk of malignancy (ROM) among ITNs. <b><i>Methods:</i></b> This prospective observational study included 1024 consecutive ITNs that underwent reflexive ThyroSPEC MT between Jul 30, 2020, and Oct 30, 2023. A multivariable logistic regression model was built to assess the relationship between histology outcomes and clinical variables, including nodule discovery by palpation, ultrasound risk categories, maximum nodule size, Bethesda category, Bethesda atypia, and ThyroSPEC categories. A total of 332 out of 1024 patients who underwent surgery and had complete data for all variables were included in the model. A nomogram was subsequently developed based on the model. <b><i>Results:</i></b> The model achieved a cross-validated AUC of 0.831 (95% confidence intervals: 0.787-0.874). Patients with high-risk mutations or malignant molecular markers exhibited significantly higher odds (152.79 times) of malignancy compared to those with mutation-negative or benign molecular marker results. Patients with maximum nodule size >5 cm have 4.34 times higher odds of malignancy than those 0-2 cm. The presence of nuclear atypia increased the odds of malignancy by 4.26 times, while ultrasound malignancy risk category 5 increased the odds of malignancy by 2.89 times compared to categories 1-3. Positive palpation discovery increased the odds by 1.83 times. The integrated ROM estimated from the regression model is significantly associated with the surgery type (<i>p</i> < 0.001). In the low (0-30%) and intermediate ROM (31-70%) categories, lobectomy alone is the most common surgery (61% and 70%, respectively), while in the high ROM (>70%) category, total thyroidectomy dominates (62%). <b><i>Conclusions:</i></b> Although MT alone played an important role in decision-making regarding surveillance versus surgery in our study population, integrating MT results with additional clinical variables improved the malignancy risk prediction for ITNs. Our results highlight the importance of contextualizing MT results within an integrated interdisciplinary thyroid nodule diagnostic pathway.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"508-515"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 2024 World Medical Association Declaration of Helsinki and Its Importance for Thyroidology.","authors":"Joseph Tobias, Megan K Applewhite, Peter Angelos","doi":"10.1089/thy.2025.0181","DOIUrl":"10.1089/thy.2025.0181","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"457-459"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Current State of Thyroid Hormone Testing in Human Serum-Results of the Free Thyroxine and Thyrotropin Interlaboratory Comparison Study.","authors":"Ashley Ribera, Otoe Sugahara, Tatiana Buchannan, Norma Vazquez, Alicia N Lyle, Li Zhang, Uliana I Danilenko, Hubert W Vesper","doi":"10.1089/thy.2024.0728","DOIUrl":"10.1089/thy.2024.0728","url":null,"abstract":"<p><p><b><i>Background:</i></b> Performance of thyroid function assays can vary significantly. To address this issue, the Centers for Disease Control and Prevention (CDC) Clinical Standardization Programs conducted an interlaboratory comparison of free thyroxine (fT4) immunoassays (IAs) and laboratory-developed tests (LDTs). This assessment aimed to determine the current performance characteristics of these assays as a first step toward measurement standardization. Thyrotropin (TSH) IAs were also evaluated. <b><i>Methods:</i></b> Assays measured 41 blinded individual-donor sera, including a sample from a pregnant woman (for fT4 analysis only) and three serum pools, with 11.3-32.1 pmol/L (0.881-2.49 ng/dL) fT4 and 0.337-21.6 mIU/L TSH in duplicate over 2 days. Passing-Bablok regression analysis performed pre-recalibration compared assays performance to the CDC fT4 reference measurement procedure (RMP) or TSH all-lab mean (ALM). Additionally, the impact of linear regression-based recalibration of assays to the CDC fT4 RMP or TSH ALM was estimated. Inter-assay agreement of sample classification according to the assay-specific reference interval (RI) was assessed pre- and post-recalibration. <b><i>Results:</i></b> A total of 21 fT4 and 17 TSH assays participated. Pre-recalibration, median biases of TSH measurements to the ALM were -1.2% [confidence interval or CI -1.8% to -0.4%], and good classification agreement among TSH assays was observed. fT4 assays all showed a negative median bias to the RMP, with higher bias among IAs (median: -20.3%, CI [-21.5% to -19.4%]) than LDTs (median: -4.5%, [CI -6.1% to -3.2%]). Of the individual-donor sera, only 21 out of 40 samples were classified uniformly by all fT4 assays, indicating poor inter-assay agreement. Post-recalibration, agreement improved to 33 out of 40 individual-donor sera correctly classified by all tested IAs and LDTs. Similar improvement in post-recalibration median percent bias was observed for fT4 IAs (median: -0.2, [CI -1.2% to 0.6%]) and LDTs (median: -0.3%, [CI -2.5% to 1.4%]). <b><i>Conclusions:</i></b> The comparison among fT4 assays emphasizes the need for measurement standardization to improve accuracy and comparability. This and previous studies demonstrate the possibility to develop common fT4 RIs via standardization, enabling the use of evidence-based clinical guidelines universally in patient care. Recalibration can effectively address high variability in fT4 assays, ensuring consistent diagnostic classification.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"471-484"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Kakudo et al.: \"High Rates of Unnecessary Surgery for Indeterminate Thyroid Nodules in the Absence of Molecular Test and the Cost-Effectiveness of Utilizing Molecular Test in an Asian Population: A Decision Analysis\".","authors":"Man Him Matrix Fung, Ching Tang, Gin Wai Kwok, Tin Ho Chan, Yan Luk, David Tak Wai Lui, Carlos King Ho Wong, Brian Hung Hin Lang","doi":"10.1089/thy.2025.0150","DOIUrl":"10.1089/thy.2025.0150","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"597-598"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reimagining the Therapeutic Approach for Anaplastic Thyroid Cancer: The Roadmap to a Cure.","authors":"Maria E Cabanillas, Neal Akhave, Victoria Banuchi, Naifa Busaidy, Ramona Dadu, Renata Ferrarotto, Gary B Gunn, Sarah Hamidi, Marie-Claude Hofmann, S Mohsen Hosseini, Priyanka C Iyer, Stephen Y Lai, Anna Lee, Anastasios Maniakas, Matthew S Ning, Michael Spiotto, Jennifer R Wang, Michelle D Williams, Mark Zafereo","doi":"10.1089/thy.2025.0044","DOIUrl":"10.1089/thy.2025.0044","url":null,"abstract":"<p><p><b><i>Background:</i></b> Anaplastic thyroid cancer (ATC) is an aggressive cancer that leads to rapid death if left untreated. However, recent advances in ATC treatment have dramatically changed the prognosis in a select group of patients with BRAF^V600E mutations. In these patients, BRAF/MEK inhibitors have been shown to dramatically and rapidly shrink tumors. Yet, these responses are short-lived unless additional treatment modalities are applied. In patients without a BRAF^V600E mutation, the current available therapies are far less effective. <b><i>Summary:</i></b> In this article, we review the relevant literature and propose applying the \"Total Therapy\" approach used since the 1960s for another deadly but curable disease, acute lymphocytic leukemia, to ATC. We have adapted the concepts of Induction, Consolidation, and Maintenance, applying them to ATC. This regimen integrates the treatments we have found to be successful in ATC: combination systemic therapy using targeted therapy plus immunotherapy, surgery, radiation, and continuation of the systemic therapy for several years, thereby attempting to eradicate all residual ATC cells. <b><i>Conclusions:</i></b> There has been a renewed interest in understanding the genomics of ATC and treating these patients with urgency rather than just providing palliative care. This shift has led to significant improvements in the prognosis of ATC. With the right tools and a clear roadmap to guide us, we now aim to take on the challenge of curing these patients.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":"35 5","pages":"462-470"},"PeriodicalIF":6.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Characterization of Highly Potent and Isoenzyme-Selective Inhibitors of Deiodinase Type I via a Nonradioactive High-Throughput Screening Method.","authors":"Rajas Sane, Carola Seyffarth, Sabrina Kleissle, Martin Neuenschwander, Jens Peter von Kries, Caroline Frädrich, Kostja Renko, Eva K Wirth, Josef Köhrle","doi":"10.1089/thy.2025.0036","DOIUrl":"10.1089/thy.2025.0036","url":null,"abstract":"<p><p><b><i>Objective:</i></b> Deiodinase type I (DIO1) is crucial in maintaining thyroid hormone (TH) balance. It converts the prohormone thyroxine (T4) to the active triiodothyronine (T3) and degrades T3 to inactive 3,3'-diiodothyronine (3,3'-T2). It also acts on reverse T3 (rT3) and sulfated TH metabolites, thus contributing to TH elimination. Upregulation of DIO1 is linked to hyperthyroid conditions such as Graves' disease and autonomous thyroid adenoma, making it a promising target for pharmacological intervention. The adverse side effects of the antithyroid drug propylthiouracil (PTU), used in clinics to treat hyperthyroidism due to its thyroid peroxidase- and DIO1-blocking action, highlight the need for novel and potent DIO1-selective inhibitors. <b><i>Methods:</i></b> Using a semiautomatic high-throughput screening (HTS) assay based on the Sandell-Kolthoff (SK) reaction in 384-well plates, we screened 69,344 low-molecular-weight compounds for DIO1-inhibitory effects. Shortlisted hits underwent detailed manual characterization, where we evaluated the potency and isoenzyme specificity by assessing their DIO-inhibitory effects on enzyme preparations from all three DIO isoenzymes, over a wide concentration range (5 nM-20 µM). To evaluate the DIO1 inhibitory effects in intact cells, we applied a novel protocol based on the SK reaction to cell culture supernatants and assessed the intracellular deiodinase activity in DIO1 overexpressing HEK293 cells. <b><i>Results:</i></b> The robust HTS assay flagged 436 (<1%) of the screened compounds as hits, also including known DIO1 inhibitors such as PTU and genistein. Based on a validation screen of 298 compounds, we prioritized 26 compounds to comprehensively characterize their DIO1-selective inhibition. We identified 15 DIO1-selective compounds (IC₅₀ < 1 µM), more potent than the bonafide DIO1-selective inhibitor PTU. Additionally, 8 of the 13 tested compounds were found capable of inhibiting DIO1 in intact cells. <b><i>Conclusions:</i></b> With a successful SK-reaction-based HTS application, we identified novel, potent, and selective inhibitors of DIO1 with nanomolar IC₅₀ values. Furthermore, we successfully showed that some of these compounds were also capable of inhibiting intracellular DIO1 in intact cells. These novel compounds hold immense potential in studying TH modulation, deciphering DIO1 enzyme structure, and developing structure-activity relationships. Furthermore, our novel inhibitors act as lead compounds in developing strategies to combat hyperthyroidism.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"576-589"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Dynamics and Prognostic Implications in Metastatic Differentiated Thyroid Cancer.","authors":"Helena Rodríguez-Lloveras, Carles Zafon, Carmela Iglesias, Jennifer Marcos-Ruiz, Joan Gil, Anna Rueda-Pujol, Lorena González, Regina Mayor, Esther N Klein Hesselink, Bettien M van Hemel, Cristina Carrato, Cecília Perelló-Fabregat, Javier Hernández-Losa, Rosa Somoza, Raquel Pluvinet, Jose F Sánchez-Herrero, Lauro Sumoy, Joan Seoane, Garcilaso Riesco-Eizaguirre, Cristina Montero-Conde, Mercedes Robledo, Jorge Hernando, Jaume Capdevila, Jordi L Reverter, Manel Puig-Domingo, Thera P Links, Mireia Jordà","doi":"10.1089/thy.2024.0303","DOIUrl":"10.1089/thy.2024.0303","url":null,"abstract":"<p><p><b><i>Background:</i></b> Distant metastases (DM) are the leading cause of thyroid cancer-related death in patients with differentiated thyroid cancer (DTC). Despite significant progress in understanding DNA methylation in DTC, the methylation landscape of metastatic primary tumors and DM remains unclear. Our primary objective was to investigate DNA methylation dynamics during DTC progression, with a secondary goal of assessing potential clinical implications. <b><i>Materials and Methods:</i></b> We conducted a multicenter retrospective study in patients with DTC who underwent surgery at five university hospitals. We profiled DNA methylation in a discovery series of 97 samples (15 normal tissues, 30 non-metastatic [non-mDTC], and 35 metastatic [mDTC] primary DTC, and 17 paired metastases [lymph nodes and DM]). Results were validated in an independent series of 17 non-mDTC and 13 mDTC. We used receiver operating characteristic curve analysis to evaluate the identified prognostic CpG-signature. <b><i>Results:</i></b> DNA methylation alterations, mostly hypomethylation, increased progressively from primary tumors to DM, both in papillary (PTC) and follicular (FTC) thyroid carcinomas. Compared with normal tissue, non-metastatic primary PTC (non-mPTC) exhibited more hypomethylated than hypermethylated CpGs in contrast to non-metastatic primary FTC (non-mFTC). However, metastatic tumors, both mPTC and mFTC, predominantly exhibited hypomethylated CpGs. The overlap of differentially methylated CpGs (DMe-CpGs) was low between non-mPTC and non-mFTC (14% non-mPTC DMe-CpGs present in non-mFTC) but significantly higher between mPTC and mFTC (60% mPTC DMe-CpGs present in mFTC), underscoring the convergence of epigenetic changes during metastatic progression. The presence of many <i>de novo</i> DMe-CpGs from metastatic primary tumors (83% from mPTC and 40% from mFTC) in DM, including metachronous DM, supports the hypothesis that DM originates from a major subclone of the primary tumor. We identified and validated a 156-CpG signature in primary tumors capable of distinguishing between non-mDTC and mDTC, offering potential prognostic value for DM development regardless of histology. <b><i>Conclusions:</i></b> These results show a progressive increase in DNA methylation alterations, mainly hypomethylation, during PTC and FTC metastatic progression, suggesting a linear model, though the DNA methylation dynamics differs between the two histological types. The analysis of the 156-CpG signature in primary tumors may help identify patients with DTC at high risk for DM, enhancing a more personalized treatment.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"494-507"},"PeriodicalIF":5.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Risk for Iatrogenic Thyrotoxicosis Among Older Adults: An Analysis from Real-World Clinical Data.","authors":"Roy Adams, Jennifer Sophie Mammen","doi":"10.1089/thy.2024.0604","DOIUrl":"10.1089/thy.2024.0604","url":null,"abstract":"<p><p><b><i>Background:</i></b> Overtreatment with thyroid hormone is common and is associated with multiple adverse health outcomes, especially in older adults. Higher overtreatment rates have been reported among women. Understanding this sex difference could lead to better clinical utilization of therapy in at-risk populations. <b><i>Methods:</i></b> We performed a retrospective cohort study to examine the relationship between iatrogenic thyrotoxicosis and patient sex, adjusting for demographics, comorbidities, body composition, and thyroid hormone dosing using electronic health records for adults age 50 and older in a large community health system in the United States. <b><i>Results:</i></b> A total of 20,724 patients met all inclusion criteria, of whom 77% were female and 23% non-White. Women were more likely to have a low thyrotropin (TSH) compared to men (36.7% vs. 23.9%; unadjusted hazard ratio [HR] = 1.67 [95% confidence interval {CI} 1.56-1.79]). Many covariates varied by sex, including rates of several comorbidities, and there was a small but statistically significant difference in the median daily levothyroxine dose per actual body mass: 1.1 μg/kg in male patients compared with 1.2 μg/kg in female patients (<i>p</i> < 0.001). Adjusting for covariates other than dose did not significantly change the sex-related risk of iatrogenic thyrotoxicosis. In fully adjusted Cox models including dose per actual body mass, the female versus male HR = 1.50 [CI 1.34-1.69] was also not different from models which did not account for dose (<i>p</i> = 0.422). However, the association between female sex and thyrotoxicosis risk was partially mediated when adjusting for dose per ideal body mass (HR = 1.30 [CI: 1.16-1.46]; <i>p</i> < 0.001) and was fully mediated by dose calculated using lean body mass (HR = 1.06 [CI: 0.95-1.19]; <i>p</i> < 0.001). That is, women had higher risk of iatrogenic thyrotoxicosis compared to men receiving similar actual body mass doses, whereas women and men receiving comparable lean body mass doses had comparable risk. <b><i>Conclusions:</i></b> Mediation analysis demonstrates that the increased risk of iatrogenic thyrotoxicosis in older women may be attributable to differences in body composition between men and women. The use of ideal or lean body weight-based dose calculators in place of actual body weight dosing could reduce this potential source of iatrogenic thyrotoxicosis risk in older women.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"485-493"},"PeriodicalIF":6.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}