Thyroid最新文献

{"title":"Micro-Costing Analysis of Thyroid Radiofrequency Ablation Compared with Hemithyroidectomy in Outpatient and Inpatient Settings.","authors":"Harrison Gao, David Forner, Ben B Levy, Pabiththa Kamalraj, Roshan Puri, Kevin M Higgins, Justine Philteos, Antoine Eskander","doi":"10.1177/10507256261474364","DOIUrl":"10.1177/10507256261474364","url":null,"abstract":"<p><strong>Background: </strong>Thyroid radiofrequency ablation (RFA) is a minimally invasive treatment for thyroid nodules. However, the health system costs of thyroid RFA are not well defined in the current literature. As its use expands, the objective of this study was to conduct a micro-costing analysis comparing RFA and hemithyroidectomy in outpatient and inpatient settings.</p><p><strong>Methods: </strong>A retrospective micro-costing analysis of 112 hemithyroidectomies and 42 thyroid RFAs was performed between January 2023 and May 2025 at two tertiary hospitals in Toronto, Canada. Costs were calculated in 2025 Canadian Dollars from the perspective of a publicly funded, single-payer health care system using a bottom-up approach across a one-year patient care cycle from initial consultation to one year of follow-up. Deterministic one-way sensitivity analyses were performed to assess cost-equivalence thresholds and the impact of procedural volume, repeat ablation, and delayed future surgery.</p><p><strong>Results: </strong>The base-case cost of RFA was $3985.05 over a one-year care cycle, including initial consultation and follow-up. RFA procedure costs accounted for $3107.61 (78.0%), which were primarily driven by consumables and supplies ($2022.21, 50.7%). Mean hemithyroidectomy costs were $4730.48 for outpatient cases and $5739.39 for inpatient cases, with an overall mean cost of $5613.28 across a one-year care cycle. For all hemithyroidectomy cases, procedure costs were driven primarily by operating room facility fees ($2344.86, 41.8%), physician fees for the surgeon and anesthesiologist ($943.38, 16.8%), and laboratory and pathology services ($486.12, 8.7%). Sensitivity analyses demonstrated that cost equivalence between RFA and outpatient hemithyroidectomy occurred when 13.3% of patients required delayed surgery and 18.7% required repeat RFA. For inpatient hemithyroidectomy, cost equivalence was reached when 31.3% required delayed surgery and 44.0% required repeat RFA.</p><p><strong>Conclusions: </strong>Over one year, the base-case cost for thyroid RFA was $1628.23 lower (29.0%) than the mean cost of all hemithyroidectomies. The cost savings of thyroid RFA are driven by eliminating the need for operating room and inpatient admission resources. Nodule regrowth requiring repeat ablation or delayed surgery is a critical factor that significantly affects the overall cost of RFA. Ultimately, proper patient selection, ablation technique, and evidence-informed implementation are needed to fully realize RFA's clinical and economic benefits.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"951-960"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654016","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":"Central Thyroid Hormone Deprivation Disrupts Cortical Cilia and Oligodendrocyte Lineage in an Allan-Herndon-Dudley Syndrome Mouse Model.","authors":"Anna Molenaar, Ekta Pathak, Miriam Bernecker, Noémi Mallet, Ruth Gutierrez-Aguilar, Cristina Mencias, Dominik Lutter, Meri De Angelis, Gandhari Maity-Kumar, Peter Kühnen, Benedikt Obermayer, Robert Opitz, Timo D Müller, Sonja C Schriever, Paul T Pfluger","doi":"10.1177/10507256261475205","DOIUrl":"10.1177/10507256261475205","url":null,"abstract":"<p><strong>Background: </strong>Allan-Herndon-Dudley syndrome (AHDS) is an X-linked neurodevelopmental disorder caused by loss of the thyroid hormone (TH) transporter MCT8, resulting in central TH deprivation and disrupted cortical maturation, cognition, and motor control. MCT8/OATP1C1 double-knockout (dKO) mice faithfully model the human disease, recapitulating its postnatal hypomyelination, neuromotor impairment, and cortical defects. Yet, cell-type-specific pathologies underlying AHDS remain insufficiently defined.</p><p><strong>Methods: </strong>To uncover cellular perturbations by TH deprivation, we performed single-nucleus RNA sequencing on cortex and attached cerebral nuclei from P21 WT and dKO mice. Differential gene expression, trajectory, pseudotime and gene-set enrichment analyses, and NeuronChat-based cell-cell communication modeling were integrated with LC-MS/MS-based TH quantification, immunofluorescence, and RNAscope.</p><p><strong>Results: </strong>In 48 clusters identified across cortical and striatal regions, we found increased numbers of GABAergic striatal D1 and D2 neurons in dKO mice, whereas mature oligodendrocytes were reduced. Trajectory analysis uncovered a bifurcation within the oligodendrocyte lineage, separating WT and dKO maturation paths and producing a dKO branch with gene profiles reminiscent of a stress-responsive, demyelination-prone state, despite largely preserved expression of core myelination genes. Trajectory analyses revealed shifted pseudotime states and distinct gene expression profiles in glutamatergic intratelencephalic and corticothalamic lineages of dKO mice. Differential gene expression patterns showed limited correspondence to Slc16a2 or Slco1c1 transcript levels but aligned strongly with published TH deprivation datasets, validating our findings and indicating that cellular perturbations are largely established by P21. Cell-cell communication analysis revealed a network imbalance favoring GABAergic over glutamatergic signaling, accompanied by altered neurexin-neuroligin interactions. In parallel, we identified a coordinated dysregulation of cilia-related genes, together with changes in cilia length and number.</p><p><strong>Conclusions: </strong>Our findings provide the first single-cell-level cortical map of AHDS brain pathology, revealing cilia defects, excitation-inhibition imbalance, differing pseudotime trajectories in glutamatergic neuronal populations and altered oligodendrocyte maturation, with actionable candidate genes such as Lama2, Litaf, and Dcc, as promising targets for future mechanistic and therapeutic exploration in AHDS. Slc16a2 and Slco1c1 transcript abundance alone did not predict cellular vulnerability, highlighting TH availability rather than transporter expression as key determinant of cell-type sensitivity and core mechanism for cortical network homeostasis.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"1005-1020"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702229","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":"Prognostic Stratification of Brain Metastases from Nonanaplastic Follicular Cell-Derived Thyroid Carcinoma: Results of an International Multicenter Retrospective Study.","authors":"Antonio Prinzi, Evert F S van Velsen, Jolanta Krajewska, Magdalena Kolton, Inbar Finkel, Liyona Kampel, Barbara Kiesewetter, Ladislaia Wolff, Mouhammed Amir Habra, Vania Balderrama-Brondani, Won Gu Kim, Chae A Kim, Christine Spitzweg, Viktoria Florentine Koehler, Merel Tessa Stegenga, Wouter T Zandee, Thera P Links, Ana Luiza Maia, Rafael Selbach Scheffel, Jason Sheehan, Matti L Gild, Fabian Pitoia, Jan Jiskra, Rajeev Parameswaran, Ralf Paschke, Roman Liscak, Ali S Alzahrani, Jonathan Wadsley, W Edward Visser, Francesco Frasca, Pasqualino Malandrino","doi":"10.1177/10507256261473771","DOIUrl":"10.1177/10507256261473771","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BMs) from nonanaplastic follicular cell-derived thyroid carcinoma (hereinafter referred to as non-ATC) are rare and not well characterized, with limited evidence guiding treatment and prognostic stratification. We aimed to describe clinical features, treatment patterns, and outcomes of patients with BMs from non-ATC and to develop and validate a disease-specific prognostic score.</p><p><strong>Methods: </strong>This retrospective international multicenter study included adults with histologically confirmed non-ATC and radiologically documented BMs treated at 19 tertiary referral centers. Clinical, radiological, treatment, and outcome data were collected. Independent predictors of progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression, and variables identified were used to develop a disease-specific Graded Prognostic Assessment (non-ATC GPA), exploratorily assessed in an independent SEER cohort.</p><p><strong>Results: </strong>A total of 189 patients were included; median age at BM diagnosis was 59 years (interquartile range [IQR] 48-67). First-line BM treatments included stereotactic radiosurgery (27.0%), neurosurgery (23.8%), whole-brain radiotherapy (18.5%), and best supportive care (10.6%). Median PFS was 7.0 months (IQR: 2.9-22.4), and median OS was 15.0 months (IQR: 4.0-38.4). Independent predictors of shorter OS were age >75 years, Eastern Cooperative Oncology Group performance status ≥2, papillary histology, extracranial metastases, and ≥4 BM. The GPA stratified patients into four prognostic groups with median OS ranging from 72.6 months in the highest-score group to 3.7 months in the lowest. An exploratory SEER-based assessment showed survival differences across adapted prognostic groups (<i>p</i> = 0.036), although this analysis was limited by the absence of all key GPA variables.</p><p><strong>Conclusions: </strong>BMs from non-ATC are associated with poor survival and marked prognostic heterogeneity. The proposed GPA may provide a useful framework for prognostic stratification, pending further validation in independent datasets to support individualized management.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"940-950"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663319","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":"Trends in Management and Outcomes of Pediatric Hyperthyroidism Over Two Decades.","authors":"Tal Oron, Michal Yackobovitch-Gavan, Liora Lazar, Naama Fisch-Shvalb","doi":"10.1177/10507256261462523","DOIUrl":"10.1177/10507256261462523","url":null,"abstract":"<p><strong>Background: </strong>Over recent decades, variations have been observed in the incidence of pediatric hyperthyroidism (HT) and Graves' disease (GD), preferred treatment modalities, and long-term outcomes. This study aimed to evaluate trends and long-term outcomes of pediatric HT across a 20-year period in a large cohort.</p><p><strong>Methods: </strong>We conducted a retrospective study using the electronic database of a large health maintenance organization. Children aged 2-18 years who were diagnosed with HT between 2000 and 2019, received antithyroid drugs (ATDs) for at least 6 months, and were followed up through 2024 were included in the analysis.</p><p><strong>Results: </strong>Of 5,111,304 insured children, 518 (75% females) met the inclusion criteria. The median age at diagnosis was 15.1 (13.0-16.5) years, and the median follow-up was 10.4 (6.5-15.1) years. The median ATD treatment duration was 3.8 (1.8-6.6) years. The mean initial methimazole dose decreased from 15.8 (8.5-23.4) mg/day in 2000-2009 to 12.9 (7.3-19.4) mg/day in 2010-2019 (<i>p</i> = 0.030). The overall remission rate was 31.1%. Compared with children diagnosed in 2000-2009, those diagnosed in 2010-2019 were less likely to undergo definitive treatment (27.5% vs. 59.6%, <i>p</i> < 0.001) and had higher nonremission (19.0% vs. 3.8%, <i>p</i> < 0.001) and relapse rates (15.9% vs. 4.6%, <i>p</i> < 0.001). Among the 161 children achieving remission, the median time to remission was 2.36 years. Younger age and antithyroid peroxidase positivity were associated with later remission (<i>p</i> = 0.010 and <i>p</i> = 0.018, respectively). Higher baseline free thyroxine levels at diagnosis were found in children with late remission than in those with early remission (42.4 [26.7-61.5] vs. 32.6 [24.4-42.5] pmol/L<i>, p</i> = 0.014).</p><p><strong>Conclusions: </strong>Over the past two decades, the management of pediatric HT has evolved toward more prolonged medical therapy and decreased reliance on definitive treatments. This change in practice appears to coincide with an increased relapse rate, underscoring the clinical implications of these changes. Future studies should focus on evaluating the influence of these treatment strategies on the long-term prognosis of children with pediatric HT.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"970-978"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319078","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":"Does Thyroid Hormone Boost Energy and Plasticity in the Brain as a Mechanism of Action in Antidepressant Augmentation Therapy?","authors":"Roger S McIntyre, Sanjay J Mathew, Thomas S Scanlan","doi":"10.1177/10507256261448290","DOIUrl":"10.1177/10507256261448290","url":null,"abstract":"<p><strong>Background: </strong>Depression is a large and expanding worldwide unmet clinical need that has proven difficult to treat. Thyroid hormone has been used clinically for decades as an augmentation therapy to first-line antidepressants, although the mechanism of action (MOA) behind the beneficial effect of thyroid hormone augmentation is not clear. Here we present a narrative review of the literature to provide an understanding of the known pathophysiology that occurs in depression and the different actions that thyroid hormone promotes in the brain to develop new insight into the mechanism behind the antidepressant activity of thyroid hormone.</p><p><strong>Summary: </strong>We believe this review of published literature illustrates the complex picture of depression pathophysiology and provides new insight into the MOA of thyroid hormones used as augmentation therapy to antidepressants. Impaired monoaminergic neurotransmission is an established pathophysiological hallmark of depression. However, there are other pathways that are impacted, including inflammatory and endocrine responses. Brain bioenergetics is affected, with depressed patients having lower brain ATP levels than healthy subjects. In addition, and perhaps related, depression patients display a loss in brain volume, particularly in the mood control regions of the brain. This is brought about by a dampening in neuroplasticity, the process by which new dendrites and synapses are formed. Here the connection to thyroid hormone augmentation becomes intriguing because thyroid hormone is known to play a role in stimulating neuroplasticity. At the target gene level, brain-derived neurotrophic factor, an initiator and biomarker of neuroplastic changes, is positively regulated by thyroid hormone, as are some of the immediate-early genes implicated in driving neuroplasticity. Thyroid hormone induces neuroplasticity and brain remodeling in a mouse model of behavior associated with increased decision-making and exploration, as well as mouse models of traumatic brain injury and stroke.</p><p><strong>Conclusions: </strong>We propose that thyroid hormone augmentation of antidepressant therapy works by stimulating the processes of neuroplasticity in the regions of the brain that are affected by depression, restoring synaptic connections lost from depression. Since neuroplasticity is an energy-demanding process, the cellular increase in brain bioenergetics stimulated by thyroid hormone action likely drives the initiation and maintenance of plasticity.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"827-831"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820758","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":"Altered Craniofacial and Bone Morphology in Hyperthyroid Knock-In Mice Carrying TSHR D633H and M453T Mutations.","authors":"Kristiina Makkonen, Jorma Määttä, Kaisa K Ivaska, Konrad Patyra, Vladyslav Melnyk, Veli Linnossuo, Johanna O Ojala, Rowmika Ravi, Holger Jaeschke, Hendrik J Undeutsch, Ralf Paschke, Jukka Kero","doi":"10.1177/10507256261463218","DOIUrl":"10.1177/10507256261463218","url":null,"abstract":"<p><strong>Background: </strong>Constitutively active mutations (CAMs) in the thyrotropin receptor (TSHR) are the major cause of nonautoimmune hyperthyroidism. TSHR is a key regulator of thyroid hormone synthesis, which is essential for skeletal formation, bone turnover, and craniofacial development. In addition to its role in thyroid hormone regulation, thyrotropin and its receptor have been proposed to independently influence bone formation and resorption. However, the specific effects of constitutively active TSHR mutations on cranial and skeletal development have not been investigated in mouse models.</p><p><strong>Methods: </strong>Cranial morphometry, micro-computed tomography, and three-point bending tests were performed in established TSHR knock-in mouse models carrying patient-derived TSHR D633H or M453T CAMs. Homozygous TSHR D633H mice exhibit mild, transient hyperthyroidism at 2 months of age, more pronounced in females, whereas homozygous TSHR M453T mice develop a more severe, iodine-dependent hyperthyroid phenotype.</p><p><strong>Results: </strong>Both TSHR CAM lines showed altered craniofacial morphology, particularly in nasal bone dimensions, resulting in a shorter snout compared with wild-type (WT) controls. The incidence of malocclusion was significantly increased in both homozygous and heterozygous mice, regardless of sex. TSHR D633H mice displayed no significant changes in femoral or tibial bone structure or biomechanical properties. In contrast, TSHR M453T mice exhibited hyperthyroidism-dependent alterations in trabecular bone mineral density (BMD) and architecture, while cortical bone was unaffected. Body and tail lengths were unchanged in TSHR D633H mice. M453T homozygous mice had reduced tail length at weaning in an iodine-dependent manner, which normalized with age.</p><p><strong>Conclusions: </strong>This <i>in vivo</i> study demonstrates that TSHR CAM-induced hyperthyroidism alters craniofacial morphology and increases the incidence of malocclusion in mice. Structural changes and altered BMD in M453T mice were dependent on the severity of hyperthyroidism. These findings highlight the role of TSHR signaling and thyroid status in craniofacial and skeletal development, warranting further mechanistic investigation.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"912-920"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303184","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":"Menopause-Related Health Outcomes in Women with Differentiated Thyroid Carcinoma Receiving Long-Term TSH Suppression after Total Thyroidectomy.","authors":"Burcu Candemir, Safak Akın, Mustafa Candemir, Nese Ersoz Gulcelik","doi":"10.1177/10507256261442839","DOIUrl":"10.1177/10507256261442839","url":null,"abstract":"<p><strong>Background: </strong>There is uncertainty regarding whether thyroid-stimulating hormone (TSH) suppression therapy in postmenopausal women with differentiated thyroid cancer (DTC) is associated with menopause-specific health concerns. This study aimed to determine whether prolonged TSH suppression confers an additional burden on postmenopausal health by comprehensively evaluating cardiovascular health (CVH), quality of life (QoL), muscle mass, and bone health using menopause-specific assessment tools.</p><p><strong>Methods: </strong>A cross-sectional study was conducted involving three groups of postmenopausal women 107 patients with DTC receiving TSH suppression therapy following total thyroidectomy for ≥3 years, 80 women receiving levothyroxine (LT4) replacement for primary hypothyroidism, and 97 euthyroid controls. Women with cognitive impairment, a history of osteoporosis, or cardiovascular disease were excluded. CVH was assessed using Life's Essential 8 (LE8) score, carotid intima-media thickness (cIMT), and electrocardiography. QoL was assessed using the Utian QoL (UQoL) Scale, cognition by the Mini-Mental State Examination, body composition by bioelectrical impedance analysis, and bone density by dual-energy X-ray absorptiometry.</p><p><strong>Results: </strong>Women with DTC demonstrated significantly lower LE8 scores, lower UQoL scores, higher cIMT values, higher prevalence of osteoporosis, and reduced muscle mass than those in the other two groups (<i>p</i> < 0.001, <i>p</i> < 0.001, <i>p</i> < 0.001, <i>p</i> = 0.003, and <i>p</i> = 0.017, respectively). Multivariable regression analysis revealed that cumulative LT4 dose was independently associated with lower LE8 and UQoL scores (β = -0.354, <i>p</i> < 0.001; and β = -0.396, <i>p</i> < 0.001, respectively), while higher serum TSH levels were positively associated with both LE8 and UQoL scores (β = 0.271, <i>p</i> = 0.002; and β = 0.487, <i>p</i> < 0.001, respectively).</p><p><strong>Conclusions: </strong>Prolonged TSH suppression may adversely affect postmenopausal health, particularly in low-risk, disease-free women with DTC. The primary clinical implication of these findings is the need to avoid unnecessary long-term TSH suppression. Menopause-specific assessment tools may have a complementary role in selected patients in whom TSH suppression remains clinically indicated.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"880-891"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676706","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":"A Longitudinal, Real-World Study of the Relationship between Levothyroxine Dose and Suboptimal Hypothyroidism Treatment.","authors":"Matthew D Ettleson, Wen Wan, Neda Laiteerapong, Brian W Kim, Antonio C Bianco","doi":"10.1177/10507256261462468","DOIUrl":"10.1177/10507256261462468","url":null,"abstract":"<p><strong>Background: </strong>Suboptimal treatment of hypothyroidism with levothyroxine (LT4) is common and associated with adverse cardiovascular outcomes. Patients treated with LT4 doses >100 µg may be at increased risk of under- and overtreatment and therefore may benefit from more frequent thyroid stimulating hormone (TSH) surveillance. Our study aim was to determine the association between LT4 dose and the occurrence of suboptimal treatment within 6 months of a normal TSH value.</p><p><strong>Methods: </strong>A total of 4449 LT4-treated adults were included in a 6-month longitudinal study. All included patients were required to have at least 2 TSH collections over the study period at least 30 days apart. Patients were grouped according to LT4 dose (≤50, 51-100, 101-150, and >150 µg), which served as the primary exposure. Outcomes included the occurrence of TSH values outside an age-adjusted normal range and a wide range (0.1-10.0 mIU/L). Model covariates included sociodemographics, index TSH value, and a range of codiagnoses and comedications that were prevalent in the population and/or known to impact LT4 treatment. Longitudinal data were analyzed using both repeated measures (generalized estimating equations) and time-to-event (Cox proportional hazards models) methodologies. Kaplan-Meier curves were plotted to examine the incidence of out-of-range TSH values stratified by LT4 dose class.</p><p><strong>Results: </strong>The incidence of at least one out-of-range TSH value approached 25% across the entire population and exceeded 45% in the LT4 > 150 µg group. In the repeated measures analysis, a dose-dependent relationship between LT4 dose and the occurrence of TSH outside the age-adjusted range (OR: 1.98, 3.39, and 5.65 for LT4 doses of 51-100, 101-150, and >150 µg, respectively, <i>p</i>-values <0.001). Results were similar when the outcome was defined as a TSH outside 0.1-10.0 mIU/L. In the time-to-event analysis, the hazard ratios were 1.58, 2.73, and 3.08, respectively (<i>p-</i>values <0.001).</p><p><strong>Conclusions: </strong>We identified a dose-dependent relationship between LT4 dose and suboptimal treatment over a 6-month study period. It may be beneficial for medically complex patients taking high doses of LT4 to increase TSH surveillance, in particular for those with a history of suboptimal treatment.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"832-839"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273065","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":"Targeted Therapy-Induced Erythrocytosis in Thyroid Cancers: An Underrecognized Safety Signal from a Retrospective Study.","authors":"Silvia Marchesi, Rebecca Romanò, Andrea Spagnoletti, Francesco Barretta, Silvia Buriolla, Matteo De Monte, Carolina Sciortino, Sara Demurtas, Lorenzo Meschia, Imperia Nuzzolese, Cristiana Bergamini, Stefano Cavalieri, Elena Colombo, Arianna Ottini, Rosalba Miceli, Monica Salvetti, Biagio Paolini, Anna Guidetti, Monica Carpenedo, Lisa Licitra, Laura Deborah Locati, Salvatore Alfieri","doi":"10.1177/10507256261454542","DOIUrl":"10.1177/10507256261454542","url":null,"abstract":"<p><strong>Background: </strong>Antiangiogenic and targeted therapies represent the most effective systemic options for advanced thyroid cancers. In this setting, toxicity management is essential to ensure treatment adherence. Among hematological toxicities, erythrocytosis has been rarely investigated, and its clinical pattern and management remain unclear.</p><p><strong>Materials and methods: </strong>We conducted a retrospective cohort study including patients with any advanced thyroid cancer histology treated with antiangiogenic or targeted therapies between 2012 and 2023 at two Italian referral centers. Therapies included <i>RET</i> inhibitors (<i>RET</i>i: selpercatinib, pralsetinib), cabozantinib, the <i>BRAF</i>/<i>MEK</i> inhibitor combination dabrafenib + trametinib, lenvatinib, sorafenib, and vandetanib. Erythrocytosis, defined according to 2022 World Health Organization criteria, was assessed through serial hemoglobin and hematocrit measurements up to 36 months from treatment start. Associations with clinical variables, event-free survival (EFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and acute vascular events were assessed using Fisher's exact and regression models, as appropriate.</p><p><strong>Results: </strong>Among 173 screened patients, 135 were included in the final analysis (median follow-up 68.5 months). Erythrocytosis occurred in 24 patients (17.8%), with 16/24 (66.6%) experiencing recurrent events (total: 50). Median time to onset was 1.28 months (Q1-Q3: 0.76-5.14). <i>RET</i>i showed the highest incidence (46.7%), followed by vandetanib (20.7%). Among 14/24 tested patients, no <i>JAK2</i> V617F or exon 12 alterations were detected. Management involved temporary treatment interruption in 60.0% (30/50) of events, with 53.3% (16/30) resuming at a reduced dose; in selected cases (4/9, 44.4%), hematology-guided phlebotomy was performed without drug discontinuation. Erythrocytosis was not associated with EFS, OS, or ORR, but was associated with higher DCR (<i>p</i> = 0.031). Incidence of acute vascular events was comparable among patients with (8.3%) and without (14.4%) erythrocytosis.</p><p><strong>Conclusions: </strong>Erythrocytosis represents an underrecognized, early, recurrent, and indolent adverse event of antiangiogenic and targeted therapies, particularly <i>RET</i>i, in advanced thyroid cancer. Its biological mechanisms and optimal management strategies warrant further investigation.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"892-902"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319076","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":"Prognostic Significance of Detectable Antithyroglobulin Antibodies Based on Analytical Sensitivity in Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin after Radioactive Iodine Treatment.","authors":"Chae A Kim, Yong-Il Kim, Dong Yun Lee, Sun-Ho Lee, Won Bae Kim, Jin-Sook Ryu, Won Gu Kim, Tae Yong Kim, Min Ji Jeon","doi":"10.1177/10507256261457026","DOIUrl":"10.1177/10507256261457026","url":null,"abstract":"<p><strong>Background: </strong>Serum thyroglobulin (Tg) is a key tumor marker in papillary thyroid carcinoma (PTC), but its reliability may be compromised by the presence of antithyroglobulin antibodies (TgAb). Utilizing the assay-specific limit of quantification (LOQ) may enhance the detection of TgAb-related interference compared with the traditional reference limit. This study evaluated postoperative TgAb levels based on LOQ as a surrogate marker for tumor monitoring in PTC.</p><p><strong>Methods: </strong>A total of 1039 patients with PTC (≥1 cm) who had undetectable unstimulated serum Tg (<0.2 ng/mL) 6-12 months after total thyroidectomy with radioactive iodine (RAI) ablation therapy (2009-2012) were retrospectively analyzed. Simultaneously measured TgAb levels were classified using both the reference limit (60.0 U/mL) and LOQ (43.4 U/mL) into three groups undetectable (<43.4 U/mL), borderline (43.4-60.0 U/mL), and elevated (>60.0 U/mL).</p><p><strong>Results: </strong>The median age was 48.2 years, and 188 (18.1%) were male. The median tumor size was 1.5 cm, and lymph node metastases were present in 705 patients (67.8%). During a median follow-up of 12.0 years, recurrence occurred in 4.8%. Based on initial TgAb level, patients were classified as undetectable (65.6%), borderline (23.5%), and elevated (10.9%), with corresponding 10-year progression-free survival rates of 97.9%, 94.6%, and 88.5%, respectively (<i>p</i> < 0.001). Multivariable analysis revealed a significantly higher recurrence risk in the borderline group compared with the undetectable group (adjusted hazard ratio, 2.01; confidence interval, 1.03-3.96; <i>p</i> = 0.043). In the borderline group, TgAb became undetectable in 75.0% of patients over 6.3 years, whereas those who remained borderline exhibited a higher recurrence rate of 12.9% (<i>p</i> = 0.01).</p><p><strong>Conclusions: </strong>TgAb levels above the LOQ were associated with a higher recurrence risk in patients with PTC with undetectable Tg after RAI treatment. Classification of TgAb positivity based on the LOQ may improve prognostic assessment compared with evaluation using conventional reference limits. Further studies are needed to validate our findings and refine TgAb thresholds.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"872-879"},"PeriodicalIF":6.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144673","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}