Pediatric Thyroid-Associated Orbitopathy: Clinical Spectrum, Systemic Implications, and Outcomes Over a 26-Year Single-Center Experience

Pediatric Thyroid-Associated Orbitopathy: Clinical Spectrum, Systemic Implications, and Outcomes Over a 26-Year Single-Center Experience | 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 Research Article Pediatric Thyroid-Associated Orbitopathy: Clinical Spectrum, Systemic Implications, and Outcomes Over a 26-Year Single-Center Experience Andrea González Espinoza, Fabiola Angelica Ogaz González This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8737401/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 Background : Thyroid-associated orbitopathy (TAO) is an uncommon extrathyroidal manifestation of Graves’ disease in children and adolescents. Compared with adults, pediatric TAO usually presents with a milder clinical course, although its systemic and psychosocial impact may be underestimated. Methods : A retrospective case series was conducted including patients younger than 18 years diagnosed with TAO between 1999 and 2025 at a tertiary ophthalmology referral center in Mexico. Demographic characteristics, clinical manifestations, diagnostic studies, treatment modalities, and outcomes were analyzed. A narrative review of the literature was also performed. Results : Seventeen patients were included (70.6% female), with a mean age at diagnosis of 12 years. The most frequent clinical manifestations were eyelid retraction (100%) and proptosis (88.2%). No cases of dysthyroid optic neuropathy or irreversible visual loss were identified. Most patients were successfully managed with conservative medical treatment and endocrinologic control. Orbital decompression surgery was required in two patients (11.7%). Clinical outcomes were favorable in all cases. Conclusions : Pediatric TAO is an infrequent condition with a generally mild ocular course. Conservative management is effective in most patients, reserving surgery for selected cases. Pediatric TAO should be regarded as part of a systemic autoimmune disorder with ocular, behavioral, and psychosocial implications distinct from adult disease. thyroid-associated orbitopathy pediatric Graves’ disease proptosis eyelid retraction children Figures Figure 1 Figure 2 Figure 3 Introduction Thyroid-associated orbitopathy (TAO), also known as thyroid eye disease, is an uncommon extrathyroidal manifestation of Graves’ disease in children and adolescents [ 1 – 3 ]. Compared with adults, pediatric patients typically exhibit a milder clinical phenotype, characterized by eyelid retraction, mild proptosis, and limited inflammatory activity. Severe complications such as dysthyroid optic neuropathy or orbital apex syndrome are rare in this population but have been reported [ 4 , 5 ]. The immunopathogenesis of TAO is largely shared across age groups and involves autoimmune activation of orbital fibroblasts mediated by the thyroid-stimulating hormone receptor, leading to downstream inflammatory and remodeling pathways [ 6 , 7 ]. Nevertheless, the clinical expression, disease course, and response to treatment in pediatric patients differ from those observed in adults, likely reflecting age-related immunologic and hormonal factors [ 2 , 3 , 8 ]. Evidence guiding management in pediatric TAO remains limited and is derived mainly from small case series, multicenter cohorts, and narrative reviews [ 3 , 5 , 9 ]. Current recommendations favor a conservative approach in most children, reserving systemic immunosuppression or surgical intervention for progressive or severe cases, in accordance with pediatric endocrine and ophthalmic guidelines [ 10 – 12 ]. Given the rarity of this condition and the paucity of long-term data, institutional experiences remain valuable. This study aims to describe the clinical spectrum, diagnostic evaluation, management strategies, and outcomes of pediatric TAO over a 26-year period, highlighting its distinctive features compared with adult disease. Methods A retrospective case series was conducted including patients younger than 18 years diagnosed with thyroid-associated orbitopathy between 1999 and 2025 at a tertiary ophthalmology referral center in Mexico. Demographic variables, clinical manifestations, diagnostic studies, treatment modalities, and outcomes were collected from medical records. A narrative review of the literature was also performed to contextualize the findings. This study adhered to institutional ethical standards and the principles of the Declaration of Helsinki. This retrospective observational study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the institutional ethics committee of the Asociación para Evitar la Ceguera en México (APEC). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived. Results Demographic characteristics of the study population are summarized in Table 1 . Table 1 Demographic characteristics of pediatric TAO cases (1999–2025) Variable n % Total patients 17 100 Female 12 70.6 Male 5 29.4 Mean age (years) 12 — Most frequent age (years) 17 — Seventeen patients were included, of whom 12 (70.6%) were female and five (29.4%) were male. Age at diagnosis ranged from 8 to 17 years, with a mean age of 12 years. The most common clinical manifestations were eyelid retraction (100%) and proptosis (88.2%). Typical orbital features similar to those observed in adult disease are shown in Fig. 1 . Diplopia and dysthyroid optic neuropathy were not observed. Five patients received exclusively medical treatment, while two patients (11.7%) required orbital decompression surgery. All patients showed favorable clinical evolution following achievement of euthyroid status, and no cases of irreversible visual loss were documented. The frequency of the main clinical manifestations is shown in Table 2 . Treatment modalities and clinical outcomes are summarized in Table 3 . Table 2 Main clinical manifestations Clinical manifestation n % Eyelid retraction 17 100 Proptosis 15 88.2 Diplopia 0 0 Dysthyroid optic neuropathy 0 0 Caruncular hyperemia 3 17.6 Table 3 Treatment modalities and outcomes Treatment n % Medical treatment only 5 29.4 Medical treatment with follow-up 10 58.9 Orbital decompression surgery 2 11.7 Favorable outcome 17 100 Discussion In our series, pediatric thyroid-associated orbitopathy represented a very small proportion of cases managed over a 26-year period. The observed female predominance and adolescent age distribution are consistent with previously published international data, including the multicenter study by Ionescu et al. Clinical presentation was predominantly mild, characterized by eyelid retraction and proptosis, with complete absence of dysthyroid optic neuropathy, supporting previous reports that severe disease is uncommon in the pediatric population. Mild clinical findings in a younger pediatric patient are shown in Fig. 2 . Beyond ocular findings, the clinical course of pediatric thyroid-associated orbitopathy in our cohort appeared to be closely linked to the systemic activity of Graves’ disease. Achievement of euthyroidism was associated not only with stabilization or improvement of orbital manifestations, but also with a general clinical improvement observed by caregivers and clinicians. This systemic–ocular relationship underscores that pediatric thyroid-associated orbitopathy should be understood as part of a multisystem autoimmune disorder rather than an isolated orbital condition. Importantly, several patients in our series exhibited non-ocular manifestations related to thyroid dysfunction, including behavioral changes such as irritability, mood fluctuations, decreased attention span, and difficulties in academic performance during periods of active disease. An example of clinically active thyroid-associated orbitopathy in an adolescent patient is illustrated in Fig. 3 . The systemic and behavioral manifestations associated with pediatric thyroid-associated orbitopathy observed in our cohort are summarized in Table 4 . Although these aspects were not formally quantified using validated behavioral or quality-of-life instruments, they were consistently reported by parents and caregivers and improved following adequate endocrinologic control. These observations are consistent with prior pediatric endocrine literature describing the neuropsychological and behavioral impact of thyroid hormone imbalance in children and adolescents. Table 4 Systemic and behavioral manifestations associated with pediatric thyroid-associated orbitopathy System involved Manifestations Clinical relevance in children General / Metabolic Weight loss, heat intolerance, increased appetite, fatigue Often precede ocular findings; related to hyperthyroid state Cardiovascular Palpitations, tachycardia May be subtle; important for systemic assessment Neuromuscular Fine tremor, muscle weakness Frequently reported during active disease Sleep regulation Insomnia, restless sleep Common and often under-recognized Neuropsychological / Behavioral Irritability, anxiety, mood swings, emotional lability Frequently reported by parents; improves after achieving euthyroidism Cognitive / Academic performance Decreased attention span, impaired concentration, poor school performance Particularly relevant in school-aged children and adolescents Autonomic Excessive sweating, heat intolerance Reflects increased sympathetic activity Growth and development Accelerated bone age, growth disturbances (rare) Related to prolonged thyroid hormone imbalance Psychosocial Reduced self-esteem, social withdrawal May be influenced by ocular appearance and systemic symptoms Footnote: Systemic manifestations are primarily related to thyroid dysfunction but frequently coexist with ocular disease activity in pediatric patients. Regarding management, the majority of patients were successfully treated with conservative medical strategies focused on systemic disease control, with surgical intervention reserved for selected cases with significant functional or cosmetic impairment. The low rate of orbital decompression in our cohort compared with other series may reflect early diagnosis, close interdisciplinary follow-up, and an emphasis on medical stabilization prior to considering surgical options. Conclusions Pediatric thyroid-associated orbitopathy is an infrequent condition with a predominantly mild ocular course; however, its clinical impact extends beyond orbital manifestations. In our 26-year single-center experience, ocular findings generally evolved in parallel with systemic thyroid dysfunction, and clinical improvement was closely associated with achieving and maintaining euthyroidism. Importantly, several patients exhibited systemic and behavioral manifestations related to thyroid disease activity, including changes in mood, irritability, decreased attention, and reduced academic performance, underscoring the broader impact of Graves’ disease in the pediatric population. Surgical intervention was required only in a small subset of patients with significant functional or cosmetic involvement. These findings highlight that pediatric thyroid-associated orbitopathy should be approached as part of a systemic autoimmune disorder with potential ocular, systemic, and psychosocial consequences. Early recognition, interdisciplinary collaboration between ophthalmology and endocrinology, and timely control of thyroid dysfunction are essential not only to optimize ocular outcomes but also to improve overall well-being, behavior, and quality of life in affected children and adolescents. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the institutional ethics committee of the Asociación para Evitar la Ceguera en México (APEC). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived. Consent for publication Written informed consent for publication of clinical images was obtained from the patients’ legal guardians. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study received no specific funding. Authors’ contributions AGE contributed to study conception and design, data collection, analysis, and drafting of the manuscript. FOG contributed to clinical supervision, interpretation of data, and critical revision of the manuscript. All authors read and approved the final manuscript. Acknowledgements None. Use of Generative Artificial Intelligence During the preparation of this manuscript, the authors used ChatGPT (OpenAI, GPT-5.2) to assist with language editing, clarification of scientific writing, and improvement of structure and style. The content was reviewed, edited, and validated by the authors to ensure accuracy, originality, and compliance with journal standards. The use of this tool did not replace the authors’ critical thinking, data interpretation, or responsibility for the final content of the manuscript. References Szczapa-Jagustyn J, Gotz-Wiƒôckowska A, Kociƒôcki J. An update on thyroid-associated ophthalmopathy in children and adolescents. J Pediatr Endocrinol Metab. 2016;29(10):1115–22. Krassas GE, Gogakos A. Thyroid-associated ophthalmopathy in juvenile Graves' disease-clinical, endocrine and therapeutic aspects. J Pediatr Endocrinol Metab. 2006;19(10):1193–206. Mendoza FC, Lacourt RP. Orbitopat√≠a de Graves en pediatr√≠a. Rev Med Chile. 2015;143(8):1034–41. Jang HJ, Jo HY. Orbital apex syndrome in pediatric thyroid eye disease: a case report and literature review. Ann Pediatr Endocrinol Metab. 2024;29(2):138–40. Ionescu IC, van Trotsenburg PAS, Paridaens D, et al. Pediatric Graves' orbitopathy: a multicentre study. Acta Ophthalmol. 2022;100(6):e1340–8. Wang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014;55(3):1735–48. Iyer S, Bahn R. Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor. Best Pract Res Clin Endocrinol Metab. 2012;26(3):281–9. Weiler DL. Thyroid eye disease: a review. Clin Exp Optom. 2017;100(1):20–5. Dong T, Fu Z, Wang X. Treating thyroid-associated ophthalmopathy in pediatric patients. Front Endocrinol (Lausanne). 2022;13:900204. Li J, et al. Pediatric hyperthyroidism and thyroid eye disease management. J AAPOS. 2023;27(3):123–8. Mooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association Guideline for the management of pediatric Graves' disease. Eur Thyroid J. 2022;11(1):e210073. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines. Eur J Endocrinol. 2021;185(4):G43–67. Additional Declarations No competing interests reported. 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-8737401","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":596735910,"identity":"8a728226-8f2c-481a-845b-f4b54075aed6","order_by":0,"name":"Andrea González Espinoza","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYHACAxDBw8/AfOAAQwGQeYBILXKSDWwJB8BsYrUYGxzgMWAgSgv/7OZtHz7UMCTObO/5eOCHgU1i3wHmh49u4NEicedY8cwZxxgS+3nObjjYY5CWOPMAm7FxDj5rbuQYM/OwAW2ZkbvhMIPB4cQNB3jYpPFpkQdp+fOPIXHD/TcPiNNiANLC2Ab0/g0eBuK0GN5IK2bs7ZOQk+xJMwD5xXjmYQJ+kbuRvJnhxzcbHn72w48//Kiwke073vzwMV7vQ4AEEpuZsPJRMApGwSgYBQQAAGkuUjBwUVQ1AAAAAElFTkSuQmCC","orcid":"","institution":"Asociación para Evitar la Ceguera en México (APEC)","correspondingAuthor":true,"prefix":"","firstName":"Andrea","middleName":"González","lastName":"Espinoza","suffix":""},{"id":596735911,"identity":"0eb4e1c4-4758-40ec-b2e9-cf86269a85ad","order_by":1,"name":"Fabiola Angelica Ogaz González","email":"","orcid":"","institution":"Asociación para Evitar la Ceguera en México (APEC)","correspondingAuthor":false,"prefix":"","firstName":"Fabiola","middleName":"Angelica Ogaz","lastName":"González","suffix":""}],"badges":[],"createdAt":"2026-01-30 05:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8737401/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8737401/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104345960,"identity":"234b160a-b4c4-4e03-9244-561ec64011e9","added_by":"auto","created_at":"2026-03-10 17:40:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":632162,"visible":true,"origin":"","legend":"\u003cp\u003eOrbital features similar to those observed in adult disease\u003c/p\u003e\n\u003cp\u003e(A) Frontal view showing eyelid retraction and mild proptosis in a 13-year-old patient at initial presentation.\u003c/p\u003e\n\u003cp\u003e(B) Upward gaze view demonstrating inferior scleral show in the same patient.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8737401/v1/a687ad9b7d93988d55a3a223.png"},{"id":104345958,"identity":"53e5e8a2-32ae-499f-a7be-ad3f003991fb","added_by":"auto","created_at":"2026-03-10 17:40:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":523716,"visible":true,"origin":"","legend":"\u003cp\u003eMild clinical findings in a younger pediatric patient.\u003c/p\u003e\n\u003cp\u003e(A) Frontal view of a 10-year-old patient showing mild eyelid retraction.\u003c/p\u003e\n\u003cp\u003e(B) Upward gaze view demonstrating right-sided proptosis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8737401/v1/4f7f233b48f864ffe7297dd2.png"},{"id":104345959,"identity":"8fabdbfb-7953-4b34-b62c-f5462254b57e","added_by":"auto","created_at":"2026-03-10 17:40:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":590904,"visible":true,"origin":"","legend":"\u003cp\u003eClinically active thyroid-associated orbitopathy\u003c/p\u003e\n\u003cp\u003e(A) Frontal view at 17 years of age showing eyelid retraction and conjunctival hyperemia at the extraocular muscle insertions\u003c/p\u003e\n\u003cp\u003e(B) Upward gaze view at 17 years of age showing bilateral proptosis\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8737401/v1/2a93348ed0235c6d839329e5.png"},{"id":105715706,"identity":"554d5322-0b7f-45fc-9b97-c3e6e0ffa19f","added_by":"auto","created_at":"2026-03-30 08:44:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3027307,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8737401/v1/7feefeb7-6eba-4c5d-b3ab-5a5837ffb922.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric Thyroid-Associated Orbitopathy: Clinical Spectrum, Systemic Implications, and Outcomes Over a 26-Year Single-Center Experience","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThyroid-associated orbitopathy (TAO), also known as thyroid eye disease, is an uncommon extrathyroidal manifestation of Graves\u0026rsquo; disease in children and adolescents [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Compared with adults, pediatric patients typically exhibit a milder clinical phenotype, characterized by eyelid retraction, mild proptosis, and limited inflammatory activity. Severe complications such as dysthyroid optic neuropathy or orbital apex syndrome are rare in this population but have been reported [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe immunopathogenesis of TAO is largely shared across age groups and involves autoimmune activation of orbital fibroblasts mediated by the thyroid-stimulating hormone receptor, leading to downstream inflammatory and remodeling pathways [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nevertheless, the clinical expression, disease course, and response to treatment in pediatric patients differ from those observed in adults, likely reflecting age-related immunologic and hormonal factors [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEvidence guiding management in pediatric TAO remains limited and is derived mainly from small case series, multicenter cohorts, and narrative reviews [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Current recommendations favor a conservative approach in most children, reserving systemic immunosuppression or surgical intervention for progressive or severe cases, in accordance with pediatric endocrine and ophthalmic guidelines [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Given the rarity of this condition and the paucity of long-term data, institutional experiences remain valuable. This study aims to describe the clinical spectrum, diagnostic evaluation, management strategies, and outcomes of pediatric TAO over a 26-year period, highlighting its distinctive features compared with adult disease.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eA retrospective case series was conducted including patients younger than 18 years diagnosed with thyroid-associated orbitopathy between 1999 and 2025 at a tertiary ophthalmology referral center in Mexico. Demographic variables, clinical manifestations, diagnostic studies, treatment modalities, and outcomes were collected from medical records. A narrative review of the literature was also performed to contextualize the findings. This study adhered to institutional ethical standards and the principles of the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003e This retrospective observational study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the institutional ethics committee of the Asociaci\u0026oacute;n para Evitar la Ceguera en M\u0026eacute;xico (APEC). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic characteristics of the study population are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of pediatric TAO cases (1999\u0026ndash;2025)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMost frequent age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSeventeen patients were included, of whom 12 (70.6%) were female and five (29.4%) were male. Age at diagnosis ranged from 8 to 17 years, with a mean age of 12 years. The most common clinical manifestations were eyelid retraction (100%) and proptosis (88.2%). Typical orbital features similar to those observed in adult disease are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Diplopia and dysthyroid optic neuropathy were not observed. Five patients received exclusively medical treatment, while two patients (11.7%) required orbital decompression surgery. All patients showed favorable clinical evolution following achievement of euthyroid status, and no cases of irreversible visual loss were documented. The frequency of the main clinical manifestations is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Treatment modalities and clinical outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMain clinical manifestations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical manifestation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEyelid retraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProptosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiplopia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysthyroid optic neuropathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaruncular hyperemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment modalities and outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical treatment only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical treatment with follow-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrbital decompression surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFavorable outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our series, pediatric thyroid-associated orbitopathy represented a very small proportion of cases managed over a 26-year period. The observed female predominance and adolescent age distribution are consistent with previously published international data, including the multicenter study by Ionescu et al. Clinical presentation was predominantly mild, characterized by eyelid retraction and proptosis, with complete absence of dysthyroid optic neuropathy, supporting previous reports that severe disease is uncommon in the pediatric population. Mild clinical findings in a younger pediatric patient are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBeyond ocular findings, the clinical course of pediatric thyroid-associated orbitopathy in our cohort appeared to be closely linked to the systemic activity of Graves\u0026rsquo; disease. Achievement of euthyroidism was associated not only with stabilization or improvement of orbital manifestations, but also with a general clinical improvement observed by caregivers and clinicians. This systemic\u0026ndash;ocular relationship underscores that pediatric thyroid-associated orbitopathy should be understood as part of a multisystem autoimmune disorder rather than an isolated orbital condition.\u003c/p\u003e \u003cp\u003eImportantly, several patients in our series exhibited non-ocular manifestations related to thyroid dysfunction, including behavioral changes such as irritability, mood fluctuations, decreased attention span, and difficulties in academic performance during periods of active disease. An example of clinically active thyroid-associated orbitopathy in an adolescent patient is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The systemic and behavioral manifestations associated with pediatric thyroid-associated orbitopathy observed in our cohort are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Although these aspects were not formally quantified using validated behavioral or quality-of-life instruments, they were consistently reported by parents and caregivers and improved following adequate endocrinologic control. These observations are consistent with prior pediatric endocrine literature describing the neuropsychological and behavioral impact of thyroid hormone imbalance in children and adolescents.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSystemic and behavioral manifestations associated with pediatric thyroid-associated orbitopathy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystem involved\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eManifestations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical relevance in children\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral / Metabolic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight loss, heat intolerance, increased appetite, fatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOften precede ocular findings; related to hyperthyroid state\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePalpitations, tachycardia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMay be subtle; important for systemic assessment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeuromuscular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFine tremor, muscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequently reported during active disease\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep regulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInsomnia, restless sleep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCommon and often under-recognized\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeuropsychological / Behavioral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIrritability, anxiety, mood swings, emotional lability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequently reported by parents; improves after achieving euthyroidism\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive / Academic performance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDecreased attention span, impaired concentration, poor school performance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eParticularly relevant in school-aged children and adolescents\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutonomic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExcessive sweating, heat intolerance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReflects increased sympathetic activity\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrowth and development\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAccelerated bone age, growth disturbances (rare)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRelated to prolonged thyroid hormone imbalance\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychosocial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReduced self-esteem, social withdrawal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMay be influenced by ocular appearance and systemic symptoms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eFootnote:\u003c/strong\u003e Systemic manifestations are primarily related to thyroid dysfunction but frequently coexist with ocular disease activity in pediatric patients.\u003c/p\u003e\u003cp\u003eRegarding management, the majority of patients were successfully treated with conservative medical strategies focused on systemic disease control, with surgical intervention reserved for selected cases with significant functional or cosmetic impairment. The low rate of orbital decompression in our cohort compared with other series may reflect early diagnosis, close interdisciplinary follow-up, and an emphasis on medical stabilization prior to considering surgical options.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePediatric thyroid-associated orbitopathy is an infrequent condition with a predominantly mild ocular course; however, its clinical impact extends beyond orbital manifestations. In our 26-year single-center experience, ocular findings generally evolved in parallel with systemic thyroid dysfunction, and clinical improvement was closely associated with achieving and maintaining euthyroidism. Importantly, several patients exhibited systemic and behavioral manifestations related to thyroid disease activity, including changes in mood, irritability, decreased attention, and reduced academic performance, underscoring the broader impact of Graves\u0026rsquo; disease in the pediatric population.\u003c/p\u003e \u003cp\u003eSurgical intervention was required only in a small subset of patients with significant functional or cosmetic involvement. These findings highlight that pediatric thyroid-associated orbitopathy should be approached as part of a systemic autoimmune disorder with potential ocular, systemic, and psychosocial consequences. Early recognition, interdisciplinary collaboration between ophthalmology and endocrinology, and timely control of thyroid dysfunction are essential not only to optimize ocular outcomes but also to improve overall well-being, behavior, and quality of life in affected children and adolescents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and approved by the institutional ethics committee of the Asociaci\u0026oacute;n para Evitar la Ceguera en M\u0026eacute;xico (APEC). Due to the retrospective nature of the study and the use of anonymized clinical data, the requirement for informed consent was waived.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eWritten informed consent for publication of clinical images was obtained from the patients\u0026rsquo; legal guardians.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study received no specific funding.\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003eAGE contributed to study conception and design, data collection, analysis, and drafting of the manuscript. FOG contributed to clinical supervision, interpretation of data, and critical revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eUse of Generative Artificial Intelligence\u003c/h2\u003e\n\u003cp\u003eDuring the preparation of this manuscript, the authors used ChatGPT (OpenAI, GPT-5.2) to assist with language editing, clarification of scientific writing, and improvement of structure and style. The content was reviewed, edited, and validated by the authors to ensure accuracy, originality, and compliance with journal standards. The use of this tool did not replace the authors\u0026rsquo; critical thinking, data interpretation, or responsibility for the final content of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSzczapa-Jagustyn J, Gotz-Wiƒ\u0026ocirc;ckowska A, Kociƒ\u0026ocirc;cki J. An update on thyroid-associated ophthalmopathy in children and adolescents. J Pediatr Endocrinol Metab. 2016;29(10):1115\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrassas GE, Gogakos A. Thyroid-associated ophthalmopathy in juvenile Graves' disease-clinical, endocrine and therapeutic aspects. J Pediatr Endocrinol Metab. 2006;19(10):1193\u0026ndash;206.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendoza FC, Lacourt RP. Orbitopat\u0026radic;\u0026ne;a de Graves en pediatr\u0026radic;\u0026ne;a. Rev Med Chile. 2015;143(8):1034\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJang HJ, Jo HY. Orbital apex syndrome in pediatric thyroid eye disease: a case report and literature review. Ann Pediatr Endocrinol Metab. 2024;29(2):138\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIonescu IC, van Trotsenburg PAS, Paridaens D, et al. Pediatric Graves' orbitopathy: a multicentre study. Acta Ophthalmol. 2022;100(6):e1340\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Smith TJ. Current concepts in the molecular pathogenesis of thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014;55(3):1735\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIyer S, Bahn R. Immunopathogenesis of Graves' ophthalmopathy: the role of the TSH receptor. Best Pract Res Clin Endocrinol Metab. 2012;26(3):281\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeiler DL. Thyroid eye disease: a review. Clin Exp Optom. 2017;100(1):20\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong T, Fu Z, Wang X. Treating thyroid-associated ophthalmopathy in pediatric patients. Front Endocrinol (Lausanne). 2022;13:900204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi J, et al. Pediatric hyperthyroidism and thyroid eye disease management. J AAPOS. 2023;27(3):123\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMooij CF, Cheetham TD, Verburg FA, et al. 2022 European Thyroid Association Guideline for the management of pediatric Graves' disease. Eur Thyroid J. 2022;11(1):e210073.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines. Eur J Endocrinol. 2021;185(4):G43\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"thyroid-associated orbitopathy, pediatric Graves’ disease, proptosis, eyelid retraction, children","lastPublishedDoi":"10.21203/rs.3.rs-8737401/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8737401/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThyroid-associated orbitopathy (TAO) is an uncommon extrathyroidal manifestation of Graves’ disease in children and adolescents. Compared with adults, pediatric TAO usually presents with a milder clinical course, although its systemic and psychosocial impact may be underestimated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eA retrospective case series was conducted including patients younger than 18 years diagnosed with TAO between 1999 and 2025 at a tertiary ophthalmology referral center in Mexico. Demographic characteristics, clinical manifestations, diagnostic studies, treatment modalities, and outcomes were analyzed. A narrative review of the literature was also performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eSeventeen patients were included (70.6% female), with a mean age at diagnosis of 12 years. The most frequent clinical manifestations were eyelid retraction (100%) and proptosis (88.2%). No cases of dysthyroid optic neuropathy or irreversible visual loss were identified. Most patients were successfully managed with conservative medical treatment and endocrinologic control. Orbital decompression surgery was required in two patients (11.7%). Clinical outcomes were favorable in all cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003ePediatric TAO is an infrequent condition with a generally mild ocular course. Conservative management is effective in most patients, reserving surgery for selected cases. Pediatric TAO should be regarded as part of a systemic autoimmune disorder with ocular, behavioral, and psychosocial implications distinct from adult disease.\u003c/p\u003e","manuscriptTitle":"Pediatric Thyroid-Associated Orbitopathy: Clinical Spectrum, Systemic Implications, and Outcomes Over a 26-Year Single-Center Experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-10 17:40:35","doi":"10.21203/rs.3.rs-8737401/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":"bf9a60f5-de83-460b-8c8a-50c8d4db3443","owner":[],"postedDate":"March 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T08:44:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-10 17:40:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8737401","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8737401","identity":"rs-8737401","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}