Incidental finding of Ectopic Retrosternal Parathyroid Adenoma in a patient operated for Controlled toxic multinodular goiter, rare case report

Incidental finding of Ectopic Retrosternal Parathyroid Adenoma in a patient operated for Controlled toxic multinodular goiter, rare case report | 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 Case Report Incidental finding of Ectopic Retrosternal Parathyroid Adenoma in a patient operated for Controlled toxic multinodular goiter, rare case report Yohannes Teshome Kassie, Solomon Lakew Ayalneh, Mekonnen Ababu Tsegaye, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8810456/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 Ectopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice but the incidentally detected retrosternal components are extremely rare. Case Presentation We present a case of a 51 years old female patient presented with anterior neck swelling of 15 years duration with hot intolerance, fatigue and palpitation in recent 2 years. She has no remarkable medical, surgical or family history. On examination during her initial visit, pulse rate was 96 beats/minute and there was bilateral multi nodular anterior neck swelling that moves with swallowing. Thyroid function test was suggestive of low thyroid stimulating hormone (TSH) for which she took anti-thyroid drugs for one year and optimized. While subtotal thyroidectomy was being done, there was about 5*3*3 centimeter oval retrosternal well encapsulated mass with no continuity with the thyroid tissue. The mass was removed with no significant difficulty and histopathologic examination was suggestive of Colloid goiter + Parathyroid adenoma. Clinical discussion Ectopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice. Most case reports shows that the incidentally detected parathyroid adenomas were at their usual anatomic location but what makes our case different is that, she was normocalcemic, the adenoma was retrosternal at anterio-superior mediastinum and very large in size (5*3*3 CM) too. Conclusion Pre-operative normocalcaemia does not preclude parathyroid disease. Any abnormally large soft tissue at the vicinity of the thyroid gland during surgery should be thoroughly evaluated and possibly excised. Ectopic retrosternal Parathyroid adenoma Thyroidectomy case report Figures Figure 1 Figure 2 Introduction Parathyroid adenomas (PA) usually arise in any of the four parathyroid glands located in their usual anatomic location in the neck, close to the thyroid gland [ 1 ]. In some instances, they can arise in ectopic locations including intrathyroidal, intrathymic, mediastinal, submandibular, and within the carotid sheath [ 1 ]. Incidentalomas are lesions which are asymptomatic and detected incidently during imaging, biochemical diagnostic test or surgery and they are a rare entity [ 2 ]. Enlargement of gland without hyperfunction may be an early stage of disease or symptoms could usually be non-specific or related to renal and skeletal system [ 2 ]. It is unusual to find an incidentally enlarged parathyroid gland during thyroid surgery accounting about 1.9% of normocalcemic patients who underwent thyroidectomies [ 2 ]. Ectopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice [ 3 ]. Presence of the mediastinal located parathyroid adenoma usually indicates the presence of multiple number of parathyroid glands [ 3 ]. Small group of patients who do not exhibit any biochemical or clinical manifestations of the disease are thought to have ‘subclinical’ hyperparathyroidism because of the appearance of the parathyroid glands [ 4 ]. These patients are only discovered by chance during surgery involving exploration of the neck usually for thyroid disease or, less frequently, during pre-operative imaging [ 3 , 4 ]. Parathyroid disease is often diagnosed when a raised calcium level is found on “routine” blood tests for other medical problems [ 7 ]. But usually, patients with Parathyroid incidentaloma are asymptomatic or suffer from nonspecific symptoms of hypercalcaemia such as fatigue, weakness, loss of appetite, nausea, and constipation [ 6 ]. In addition, there are a few patients who do not manifest either chemical or clinical hyperparathyroidism and who are only discovered incidentally during a thyroid operation [ 8 ]. Investigation of thyroid disease often includes CBC, TFT, other OFTs, ultrasonography of the neck, FNAC and in some cases with coexistent thyroid and parathyroid disease, radioisotope iodine uptake scan, serum electrolytes and serum PTH may be determined [ 7 ]. For patients with preoperative clinical or biohemical features of hypercalcemia, whole body sestamibi imaging may demonstrate increased uptake within both the ectopic locations and multiple bone lesions leading to the correct diagnosis [ 9 , 10 ]. Treatment of ectopic adenomas usually requires resection using either of the various techniques mainly depending on the ectopic gland’s location [ 5 ]. Though there is risk of removing a histologically normal gland, majority of them may be causing subclinical or early or normocalcemic hyperparathyroidism [ 6 ]. Here in, we present a 51 years old female patient with incidentally detected ectopic retrosternal parathyroid adenoma during thyroid surgery. Methods The work has been reported in line with the SCARE criteria [ 11 ]. Case presentation A 51 years old female patient presented with anterior neck swelling of 15 years duration. She also had hot intolerance, fatigue and palpitation for the last 2 years. Otherwise, she has no remarkable medical, surgical or family history. On examination during her initial visit, her pulse rate was 96 beats/minute and there was about 7*5CM left sided and 4*3CM right sided multi nodular anterior neck swelling that moves with swallowing. Thyroid function test was suggestive of low TSH but normal T3 and T4 levels. She was also investigated with neck ultrasound which shows about 7*5*3CM iso to hyperechoic lesions with coarse calcification to the left thyroid lobe and about 5*4*2CM iso to hyperechoic lesions to the right thyroid lobe suggestive of bilateral multi nodular goiter. FNAC was suggestive of benign colloid goiter. CBC, Serum electrolyte (including serum total and ionized calcium levels), RFT, LFT and ECG were all normal. With the diagnosis of Toxic multinodular goiter, she was given anti-thyroid drugs and Beta blockers (PTU and Propranolol) for 1 year and got optimized. After informed and written consent was taken, she was scheduled for thyroidectomy. Intra-operatively, after subtotal thyroidectomy was done ( left total and right subtotal), there was about 5*3*3 CM incidentally detected, solid, oval, retrosternal, well encapsulated mass with no continuity with the thyroid tissue but an areolar tissue in between the mass and the right thyroid lobe (Fig. 1 ). The recurrent laryngeal nerves and all the normally located parathyroid gland like tissues were preserved. The mass was removed with no significant difficulty and histopathologic examination was suggestive of Colloid goiter + Parathyroid adenoma (Fig. 2 ). In the immediate post-operative day, she was investigated with serum calcium (ionized, bound and total) and PTH levels which were all in normal range. Abdominal ultrasound had unremarkable findings. She had smooth post-operative course and discharged on 2nd day after surgery. On her follow up after a week, a month and then after 3 months, she had none of the possible complications and TFT and serum electrolytes were normal. Discussion Parathyroid adenomas (PA) usually arise in any of the four parathyroid glands located in their usual anatomic location in the neck, close to the thyroid gland. In some instances, they can arise in ectopic locations including intrathyroidal, intrathymic, mediastinal, submandibular, and within the carotid sheath [ 1 ]. Whenever, any surgeon encounters a macroscopically abnormal parathyroid gland during thyroid surgery, he/she faces a dilemma, whether to remove it or not [ 2 ]. Histopathologic examination of mediastinal parathyroid lesions do not differ from cervical parathyroid glands [ 2 ]. Ectopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice and they are more frequently found in females than in males (3:1 ratio) [ 2 , 3 ]. Mediastinal parathyroid glands cause hyperparathyroidism in 20% of all patients with primary hyperparathyroidism, and these glands have been incompletely removed when using the cervical approach in 2% of all patients [ 3 ]. Our case had asymptomatic (both clinically and biochemically) parathyroid adenoma at anterio-superior mediastinum. The most popular treatment method for ectopic parathyroid glands is surgical excision via a cervical incision [ 3 ]. However, this approach is not suitable when the parathyroid gland is located in either the anterior or posterior mediastinum [ 3 ]. A median sternotomy or thoracotomy have traditionally been used to treat such cases, but many surgeons have recently performed minimally invasive surgical techniques such as video assisted thoracoscopic surgery (VATS) and video assisted mediastinoscopy (VAM) and achieved surgical outcomes similar to those associated with the traditional surgical approach [ 3 ]. We detected the adenoma incidentally while doing thyroidectomy through cervical incision and removed it without extending the incision. Patients undergoing thyroid surgery should have their calcium levels checked pre-operatively but screening for primary hyperparathyroidism before thyroid surgery benefits a small number of patients, especially those who are positively screened, and in whom the parathyroid pathology is unlikely to be detected intraoperatively[ 4 ]. If calcium levels are high/ borderline high or if there is a history of radiation exposure, parathyroid hormone levels should be measured. Pre-operative normocalcaemia does not preclude parathyroid disease so inspection of the parathyroids during thyroid surgery is recommended [ 4 ]. Often parathyroid incidentalomas in the form of macroscopically enlarged single or multiple parathyroid glands are encountered during surgical thyroidectomy [ 4 , 6 ]. The reported incidence in literature is variable (0.4–4.5%) [ 6 ]. Parathyroid disease is often diagnosed when a raised calcium level is found on “routine” blood tests for other medical conditions. Usually, these patients are asymptomatic or suffer from nonspecific symptoms of hypercalcaemia such as fatigue, weakness, loss of appetite, nausea, and constipation [ 7 ]. Whole body 99mTc- sestamibi imaging may demonstrate increased uptake within both the normally located or ectopic parathyroid tissues [ 9 ]. Our case was investigated with serum electrolytes as routine investigation pre-operatively which was normal and she had none of the symptoms of hyperparathyroidism. Previous studies have suggested that enlarged parathyroid found during a thyroid operation should always be removed even if it is impossible to predict whether or not such incidental hyperparathyroidism leads to the development of true clinical hyperparathyroidism [ 9 ]. The first case of excision of ectopic mediastinal parathyroid adenoma was reported in an American sea captain who required 6 operations in 1932 [ 10 ]. Today, diagnosis and operation of ectopic parathyroid glands, especially mediastinal adenoma, continue to be a challenge [ 10 ]. Most case reports shows that the incidentally detected parathyroid adenomas were at their usual anatomic location but what makes our case different is the adenoma was retrosternal and at the anterio-superior mediastinum and very large in size (5*3*3 CM) too. There was no decision dilemma regarding its removal since we already visualized and preserved the normally located parathyroid tissues. We took blood sample in the immediate post-operative time to determine serum PTH level for possible normocalcemic hyperparathyroidism but found it normal. Conclusion Pre-operative normocalcaemia does not preclude parathyroid disease. Any abnormally large soft tissue at the vicinity of the thyroid gland during surgery should be thoroughly evaluated and possibly excised. Benign appearing, incidentally detected ectopic parathyroid tissue in anterio-superior mediastinum can be accessed through the same cervical approach with no significant difficulty. Abbreviations CBC Complete blood count CM Centimeter ECG Electrocardiography FNAC Fine needle aspiration cytology H&E Hematoxylin and Eosin OFT Organ function test PA Parathyroid adenoma PTH Parathyroid hormone PTU Propylthiouracil RFT Renal function test SCARE Surgical case reports T3:Triiodothyronine T4 Tetra iodothyronine TFT Thyroid function test TSH Thyroid stimulating hormone VAM Video assisted mediastinoscopy VATS Video assisted thoracic surgery WMA World medical association Declarations Ethical approval All procedures performed in this study involving human participants were in accordance with the declaration of Helsinki developed by The World Medical Association (WMA) and the ethical standards of the institutional and national research committee. Consent for publication Informed consent was obtained from the patient and her attendants for this study. Competing interests Authors declare that they have no competing interests. Funding The authors received no financial support for the publication and/or authorship of this article. Author Contribution Conceptualization: YT. Data collection and Methodology development: YT, SL. Data analysis: YT, YA, MA. Manuscript Draft: YT, YA, AF. Manuscript review and editing; YT, AF, YA, SL, MA. Pathologist; MA. All authors have read and approved the manuscript. Acknowledgements Not applicable. References Amr YS, Saleh MM, Amr SS. Giant ectopic parathyroid adenoma arising in the posterior mediastinum. Report of case and a review. Case Rep Surg. 2022;2022(1):6473197. Khanna S, Singh S, Khanna AK. Parathyroid incidentaloma. Indian J Surg Oncol. 2012;3(1):26–9. YAZKANA R, ÇEVİKER K, AYDIN B, İİHAN AA, ÇİRİŞ İM. Parathyroid adenoma located on anterior mediastinum. Turkish J Clin Lab. 2016;7(3):83–5. Hotouras A, Sinha P. Parathyroid incidentalomas: case report and literature review. Grand Rounds. 2007;7:45–7. Wang X, Zhu YM, Huang H, Zhang LP, Zhang Y, Wang XL. Surgery for ectopic parathyroid adenoma in lower part of superior mediastinum through a transcervical incision. Chin Med J. 2017;130(11):1376–7. Panchangam RB, Chakrapani B, Sabaretnam M. Clinical significance of parathyroid incidentalomas during thyroidectomy: a South Indian experience. In Endocrine Abstracts 2019 May 1 (Vol. 63). Bioscientifica. Helme S, Lulsegged A, Sinha P. Incidental parathyroid disease during thyroid surgery: should we remove them? Int Sch Res Notices. 2011;2011(1):962186. Ali GM. Incidental Parathyroid Adenoma: A Case Report. Saudi J Med Pharm Sci. 2021;7(6):248–50. Kirk J, Au-Yong I, Ganatra R. Multimodality imaging of a retrosternal parathyroid adenoma with multiple brown tumors. Clin Nucl Med. 2009;34(9):555–9. Alam N, Adimoolam K, Gougler P, Okwuwa I, Li W. Primary Hyperparathyroidism from an ectopic retrosternal parathyroid adenoma. Austin J Clin Case Rep. 2015;2(2):1068. Kerwan A, Al-Jabir A, Mathew G, Sohrabi C, Rashid R, Franchi T, Nicola M, Agha M, Agha RA. Revised Surgical CAse REport (SCARE) guideline: An update for the age of Artificial Intelligence. Premier J Sci 2025:10100079. 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-8810456","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":587181768,"identity":"62b6f95c-7633-43fe-a5e8-2da62f5e72b7","order_by":0,"name":"Yohannes Teshome Kassie","email":"data:image/png;base64,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","orcid":"","institution":"Wollo University","correspondingAuthor":true,"prefix":"","firstName":"Yohannes","middleName":"Teshome","lastName":"Kassie","suffix":""},{"id":587181769,"identity":"29c03ea0-acfd-4695-8e97-468f1b074a74","order_by":1,"name":"Solomon Lakew Ayalneh","email":"","orcid":"","institution":"Wollo University","correspondingAuthor":false,"prefix":"","firstName":"Solomon","middleName":"Lakew","lastName":"Ayalneh","suffix":""},{"id":587181770,"identity":"0e23d3cb-d80b-473a-bd4e-b878e09146cc","order_by":2,"name":"Mekonnen Ababu Tsegaye","email":"","orcid":"","institution":"Wollo University","correspondingAuthor":false,"prefix":"","firstName":"Mekonnen","middleName":"Ababu","lastName":"Tsegaye","suffix":""},{"id":587181771,"identity":"ce1c0a7c-f3e4-4297-8d63-f35e7422b6f5","order_by":3,"name":"Yimam Ali Mergiaw","email":"","orcid":"","institution":"Woldia University","correspondingAuthor":false,"prefix":"","firstName":"Yimam","middleName":"Ali","lastName":"Mergiaw","suffix":""},{"id":587181772,"identity":"ee410874-505c-4583-b239-7d7eaac6b39c","order_by":4,"name":"Melaku Abay Muluneh","email":"","orcid":"","institution":"Arsi University","correspondingAuthor":false,"prefix":"","firstName":"Melaku","middleName":"Abay","lastName":"Muluneh","suffix":""},{"id":587181773,"identity":"4e686757-56f7-4e9b-9d42-9bba65b9f51f","order_by":5,"name":"Atalel Fantahun Awedew","email":"","orcid":"","institution":"Debre Tabor University","correspondingAuthor":false,"prefix":"","firstName":"Atalel","middleName":"Fantahun","lastName":"Awedew","suffix":""}],"badges":[],"createdAt":"2026-02-06 19:39:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8810456/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8810456/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102311206,"identity":"441d09ba-3834-4a81-aa29-d39a7d153645","added_by":"auto","created_at":"2026-02-10 11:57:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":335322,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePicture of an excised tissue; the thyroidectomy specimen (green arrows) and the retrosternal parathyroid adenoma (pink arrow).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8810456/v1/84a16a54fe2b3dfd32744671.png"},{"id":102310689,"identity":"d574271e-a864-45e4-9f2c-0f960cee3a13","added_by":"auto","created_at":"2026-02-10 11:55:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":748632,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eH \u0026amp; E ( Hematoxylin and Eosin) stained tissue section show capsulated nodule composed of cellular sheets of chief cells displaying round nuclei and amphophilic to clear cytoplasm and oxyphil cells displaying eosinophilic abundant cystoplasm suggestive of Parathyroid adenoma histology.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8810456/v1/4c5997cee31ca028e28ec6af.png"},{"id":109163895,"identity":"b928569a-b29c-4754-b7d7-8aa5b8c05b4a","added_by":"auto","created_at":"2026-05-13 08:01:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1376030,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8810456/v1/a92994c7-4ae4-4010-b577-29b8dcd1c6b1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Incidental finding of Ectopic Retrosternal Parathyroid Adenoma in a patient operated for Controlled toxic multinodular goiter, rare case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eParathyroid adenomas (PA) usually arise in any of the four parathyroid glands located in their usual anatomic location in the neck, close to the thyroid gland [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In some instances, they can arise in ectopic locations including intrathyroidal, intrathymic, mediastinal, submandibular, and within the carotid sheath [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Incidentalomas are lesions which are asymptomatic and detected incidently during imaging, biochemical diagnostic test or surgery and they are a rare entity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Enlargement of gland without hyperfunction may be an early stage of disease or symptoms could usually be non-specific or related to renal and skeletal system [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is unusual to find an incidentally enlarged parathyroid gland during thyroid surgery accounting about 1.9% of normocalcemic patients who underwent thyroidectomies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEctopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Presence of the mediastinal located parathyroid adenoma usually indicates the presence of multiple number of parathyroid glands [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Small group of patients who do not exhibit any biochemical or clinical manifestations of the disease are thought to have \u0026lsquo;subclinical\u0026rsquo; hyperparathyroidism because of the appearance of the parathyroid glands [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These patients are only discovered by chance during surgery involving exploration of the neck usually for thyroid disease or, less frequently, during pre-operative imaging [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eParathyroid disease is often diagnosed when a raised calcium level is found on \u0026ldquo;routine\u0026rdquo; blood tests for other medical problems [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. But usually, patients with Parathyroid incidentaloma are asymptomatic or suffer from nonspecific symptoms of hypercalcaemia such as fatigue, weakness, loss of appetite, nausea, and constipation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In addition, there are a few patients who do not manifest either chemical or clinical hyperparathyroidism and who are only discovered incidentally during a thyroid operation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInvestigation of thyroid disease often includes CBC, TFT, other OFTs, ultrasonography of the neck, FNAC and in some cases with coexistent thyroid and parathyroid disease, radioisotope iodine uptake scan, serum electrolytes and serum PTH may be determined [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. For patients with preoperative clinical or biohemical features of hypercalcemia, whole body sestamibi imaging may demonstrate increased uptake within both the ectopic locations and multiple bone lesions leading to the correct diagnosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of ectopic adenomas usually requires resection using either of the various techniques mainly depending on the ectopic gland\u0026rsquo;s location [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Though there is risk of removing a histologically normal gland, majority of them may be causing subclinical or early or normocalcemic hyperparathyroidism [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere in, we present a 51 years old female patient with incidentally detected ectopic retrosternal parathyroid adenoma during thyroid surgery.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe work has been reported in line with the SCARE criteria [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eA 51 years old female patient presented with anterior neck swelling of 15 years duration. She also had hot intolerance, fatigue and palpitation for the last 2 years. Otherwise, she has no remarkable medical, surgical or family history. On examination during her initial visit, her pulse rate was 96 beats/minute and there was about 7*5CM left sided and 4*3CM right sided multi nodular anterior neck swelling that moves with swallowing. Thyroid function test was suggestive of low TSH but normal T3 and T4 levels. She was also investigated with neck ultrasound which shows about 7*5*3CM iso to hyperechoic lesions with coarse calcification to the left thyroid lobe and about 5*4*2CM iso to hyperechoic lesions to the right thyroid lobe suggestive of bilateral multi nodular goiter. FNAC was suggestive of benign colloid goiter. CBC, Serum electrolyte (including serum total and ionized calcium levels), RFT, LFT and ECG were all normal. With the diagnosis of Toxic multinodular goiter, she was given anti-thyroid drugs and Beta blockers (PTU and Propranolol) for 1 year and got optimized.\u003c/p\u003e \u003cp\u003e After informed and written consent was taken, she was scheduled for thyroidectomy. Intra-operatively, after subtotal thyroidectomy was done ( left total and right subtotal), there was about 5*3*3 CM incidentally detected, solid, oval, retrosternal, well encapsulated mass with no continuity with the thyroid tissue but an areolar tissue in between the mass and the right thyroid lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The recurrent laryngeal nerves and all the normally located parathyroid gland like tissues were preserved. The mass was removed with no significant difficulty and histopathologic examination was suggestive of Colloid goiter\u0026thinsp;+\u0026thinsp;Parathyroid adenoma (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the immediate post-operative day, she was investigated with serum calcium (ionized, bound and total) and PTH levels which were all in normal range. Abdominal ultrasound had unremarkable findings. She had smooth post-operative course and discharged on 2nd day after surgery. On her follow up after a week, a month and then after 3 months, she had none of the possible complications and TFT and serum electrolytes were normal.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eParathyroid adenomas (PA) usually arise in any of the four parathyroid glands located in their usual anatomic location in the neck, close to the thyroid gland. In some instances, they can arise in ectopic locations including intrathyroidal, intrathymic, mediastinal, submandibular, and within the carotid sheath [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Whenever, any surgeon encounters a macroscopically abnormal parathyroid gland during thyroid surgery, he/she faces a dilemma, whether to remove it or not [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Histopathologic examination of mediastinal parathyroid lesions do not differ from cervical parathyroid glands [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEctopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice and they are more frequently found in females than in males (3:1 ratio) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Mediastinal parathyroid glands cause hyperparathyroidism in 20% of all patients with primary hyperparathyroidism, and these glands have been incompletely removed when using the cervical approach in 2% of all patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Our case had asymptomatic (both clinically and biochemically) parathyroid adenoma at anterio-superior mediastinum.\u003c/p\u003e \u003cp\u003eThe most popular treatment method for ectopic parathyroid glands is surgical excision via a cervical incision [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, this approach is not suitable when the parathyroid gland is located in either the anterior or posterior mediastinum [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A median sternotomy or thoracotomy have traditionally been used to treat such cases, but many surgeons have recently performed minimally invasive surgical techniques such as video assisted thoracoscopic surgery (VATS) and video assisted mediastinoscopy (VAM) and achieved surgical outcomes similar to those associated with the traditional surgical approach [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We detected the adenoma incidentally while doing thyroidectomy through cervical incision and removed it without extending the incision.\u003c/p\u003e \u003cp\u003ePatients undergoing thyroid surgery should have their calcium levels checked pre-operatively but screening for primary hyperparathyroidism before thyroid surgery benefits a small number of patients, especially those who are positively screened, and in whom the parathyroid pathology is unlikely to be detected intraoperatively[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. If calcium levels are high/ borderline high or if there is a history of radiation exposure, parathyroid hormone levels should be measured. Pre-operative normocalcaemia does not preclude parathyroid disease so inspection of the parathyroids during thyroid surgery is recommended [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Often parathyroid incidentalomas in the form of macroscopically enlarged single or multiple parathyroid glands are encountered during surgical thyroidectomy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The reported incidence in literature is variable (0.4\u0026ndash;4.5%) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Parathyroid disease is often diagnosed when a raised calcium level is found on \u0026ldquo;routine\u0026rdquo; blood tests for other medical conditions. Usually, these patients are asymptomatic or suffer from nonspecific symptoms of hypercalcaemia such as fatigue, weakness, loss of appetite, nausea, and constipation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Whole body 99mTc- sestamibi imaging may demonstrate increased uptake within both the normally located or ectopic parathyroid tissues [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Our case was investigated with serum electrolytes as routine investigation pre-operatively which was normal and she had none of the symptoms of hyperparathyroidism.\u003c/p\u003e \u003cp\u003ePrevious studies have suggested that enlarged parathyroid found during a thyroid operation should always be removed even if it is impossible to predict whether or not such incidental hyperparathyroidism leads to the development of true clinical hyperparathyroidism [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The first case of excision of ectopic mediastinal parathyroid adenoma was reported in an American sea captain who required 6 operations in 1932 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Today, diagnosis and operation of ectopic parathyroid glands, especially mediastinal adenoma, continue to be a challenge [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMost case reports shows that the incidentally detected parathyroid adenomas were at their usual anatomic location but what makes our case different is the adenoma was retrosternal and at the anterio-superior mediastinum and very large in size (5*3*3 CM) too. There was no decision dilemma regarding its removal since we already visualized and preserved the normally located parathyroid tissues. We took blood sample in the immediate post-operative time to determine serum PTH level for possible normocalcemic hyperparathyroidism but found it normal.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePre-operative normocalcaemia does not preclude parathyroid disease. Any abnormally large soft tissue at the vicinity of the thyroid gland during surgery should be thoroughly evaluated and possibly excised. Benign appearing, incidentally detected ectopic parathyroid tissue in anterio-superior mediastinum can be accessed through the same cervical approach with no significant difficulty.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplete blood count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentimeter\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectrocardiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFNAC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFine needle aspiration cytology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH\u0026amp;E\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHematoxylin and Eosin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOFT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOrgan function test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eParathyroid adenoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eParathyroid hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePropylthiouracil\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRFT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRenal function test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCARE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e\u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSurgical case reports\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eT3:Triiodothyronine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT4\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTetra iodothyronine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTFT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThyroid function test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThyroid stimulating hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVideo assisted mediastinoscopy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVATS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVideo assisted thoracic surgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld medical association\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical approval\u003c/h2\u003e \u003cp\u003eAll procedures performed in this study involving human participants were in accordance with the declaration of Helsinki developed by The World Medical Association (WMA) and the ethical standards of the institutional and national research committee.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eInformed consent was obtained from the patient and her attendants for this study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eAuthors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e The authors received no financial support for the publication and/or authorship of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: YT. Data collection and Methodology development: YT, SL. Data analysis: YT, YA, MA. Manuscript Draft: YT, YA, AF. Manuscript review and editing; YT, AF, YA, SL, MA. Pathologist; MA. All authors have read and approved the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmr YS, Saleh MM, Amr SS. Giant ectopic parathyroid adenoma arising in the posterior mediastinum. Report of case and a review. Case Rep Surg. 2022;2022(1):6473197.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhanna S, Singh S, Khanna AK. Parathyroid incidentaloma. Indian J Surg Oncol. 2012;3(1):26\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYAZKANA R, \u0026Ccedil;EVİKER K, AYDIN B, İİHAN AA, \u0026Ccedil;İRİŞ İM. Parathyroid adenoma located on anterior mediastinum. Turkish J Clin Lab. 2016;7(3):83\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHotouras A, Sinha P. Parathyroid incidentalomas: case report and literature review. Grand Rounds. 2007;7:45\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Zhu YM, Huang H, Zhang LP, Zhang Y, Wang XL. Surgery for ectopic parathyroid adenoma in lower part of superior mediastinum through a transcervical incision. Chin Med J. 2017;130(11):1376\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePanchangam RB, Chakrapani B, Sabaretnam M. Clinical significance of parathyroid incidentalomas during thyroidectomy: a South Indian experience. In Endocrine Abstracts 2019 May 1 (Vol. 63). Bioscientifica.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHelme S, Lulsegged A, Sinha P. Incidental parathyroid disease during thyroid surgery: should we remove them? Int Sch Res Notices. 2011;2011(1):962186.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli GM. Incidental Parathyroid Adenoma: A Case Report. Saudi J Med Pharm Sci. 2021;7(6):248\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirk J, Au-Yong I, Ganatra R. Multimodality imaging of a retrosternal parathyroid adenoma with multiple brown tumors. Clin Nucl Med. 2009;34(9):555\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlam N, Adimoolam K, Gougler P, Okwuwa I, Li W. Primary Hyperparathyroidism from an ectopic retrosternal parathyroid adenoma. Austin J Clin Case Rep. 2015;2(2):1068.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKerwan A, Al-Jabir A, Mathew G, Sohrabi C, Rashid R, Franchi T, Nicola M, Agha M, Agha RA. Revised Surgical CAse REport (SCARE) guideline: An update for the age of Artificial Intelligence. Premier J Sci 2025:10100079.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Ectopic, retrosternal, Parathyroid adenoma, Thyroidectomy, case report","lastPublishedDoi":"10.21203/rs.3.rs-8810456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8810456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEctopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice but the incidentally detected retrosternal components are extremely rare.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eWe present a case of a 51 years old female patient presented with anterior neck swelling of 15 years duration with hot intolerance, fatigue and palpitation in recent 2 years. She has no remarkable medical, surgical or family history. On examination during her initial visit, pulse rate was 96 beats/minute and there was bilateral multi nodular anterior neck swelling that moves with swallowing. Thyroid function test was suggestive of low thyroid stimulating hormone (TSH) for which she took anti-thyroid drugs for one year and optimized. While subtotal thyroidectomy was being done, there was about 5*3*3 centimeter oval retrosternal well encapsulated mass with no continuity with the thyroid tissue. The mass was removed with no significant difficulty and histopathologic examination was suggestive of Colloid goiter\u0026thinsp;+\u0026thinsp;Parathyroid adenoma.\u003c/p\u003e\u003ch2\u003eClinical discussion\u003c/h2\u003e \u003cp\u003eEctopic parathyroid adenomas represent a diagnostic challenge, since they are extremely rare in clinical practice. Most case reports shows that the incidentally detected parathyroid adenomas were at their usual anatomic location but what makes our case different is that, she was normocalcemic, the adenoma was retrosternal at anterio-superior mediastinum and very large in size (5*3*3 CM) too.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePre-operative normocalcaemia does not preclude parathyroid disease. Any abnormally large soft tissue at the vicinity of the thyroid gland during surgery should be thoroughly evaluated and possibly excised.\u003c/p\u003e","manuscriptTitle":"Incidental finding of Ectopic Retrosternal Parathyroid Adenoma in a patient operated for Controlled toxic multinodular goiter, rare case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-10 11:43:48","doi":"10.21203/rs.3.rs-8810456/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":"95e1400d-375d-41cc-b9ff-dadada59b5b0","owner":[],"postedDate":"February 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T07:58:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-10 11:43:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8810456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8810456","identity":"rs-8810456","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}