[18F]Fluorocholine PET/CT in a 15-Year-Old patient suggested HPT-JT Syndrome with Active Cemento-ossifying Fibroma

[18F]Fluorocholine PET/CT in a 15-Year-Old patient suggested HPT-JT Syndrome with Active Cemento-ossifying Fibroma | 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 [18F]Fluorocholine PET/CT in a 15-Year-Old patient suggested HPT-JT Syndrome with Active Cemento-ossifying Fibroma Francesca Serani, Carmelo Salvino Lacognata, Francesca Torresan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6190034/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Jan, 2026 Read the published version in EJNMMI Research → Version 1 posted 5 You are reading this latest preprint version Abstract Background Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant disorder caused by CDC73 gene mutations, predisposing individuals to primary hyperparathyroidism (pHPT), cemento-ossifying fibromas, and other neoplastic conditions. [18F]Fluorocholine PET/CT has emerged as a tool for localizing hyperfunctioning parathyroid glands in pHPT, but its application in HPT-JT syndrome remains unreported. Case Presentation We describe the case of a 15-year-old male presenting with severe hypercalcemia, hyperparathormonemia, and a history of cemento-ossifying fibroma removal. Standard imaging, including [99mTc]Tc-MIBI scintigraphy, was inconclusive. [18F]Fluorocholine PET/CT successfully identified a hyperfunctioning parathyroid neoplasm and a recurrent maxillary cemento-ossifying fibroma. Genetic testing confirmed a CDC73 mutation, leading to the diagnosis of HPT-JT syndrome. Conclusions To our knowledge, this is the first reported case utilizing [18F]Fluorocholine PET/CT for the diagnosis and management of HPT-JT syndrome. Given its superior sensitivity compared to conventional imaging, [18F]Fluorocholine PET/CT provided critical information for surgical planning and long-term disease monitoring. This case highlights the potential role of [18F]Fluorocholine PET/CT in detecting both parathyroid and maxillary manifestations of HPT-JT syndrome, emphasizing the need for further research into its application in hereditary endocrine disorders. Figures Figure 1 Background Primary hyperparathyroidism (pHPT) is typically a sporadic disorder though it can be heritable in approximately 10% of cases; in this cases it can occur as an isolated condition or as part of a syndrome involving tumors in other tissues. Syndromes associated with pHPT include multiple endocrine neoplasia types 1 (MEN1), 2A (MEN2A) and 4 (MEN4), hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and familial isolated hyperparathyroidism (FIHP) [ 1 , 2 ]. HPT-JT is a rare autosomal dominant disease with incomplete penetrance, caused by mutations in the suppressor gene CDC73 (formerly known as HRPT2), which encodes for parafibromin [ 3 ]. This inherited endocrine neoplastic syndrome predisposes individuals to a triad of conditions including multiple maxillary or mandibular cemento-ossifying fibromas, benign and malignant parathyroid neoplasms, cystic and neoplastic renal abnormalities, and hyperplastic and neoplastic uterine involvement [ 4 ]. However, the most common - and sometimes sole - manifestation of HPT-JT is pHPT [ 4 ]. HPT-JT is more frequently associated with atypical adenomas and parathyroid carcinomas compared to other pHPT conditions [ 5 ]. Nuclear medicine techniques are crucial in identifying and localizing hyperfunctioning parathyroid glands [ 6 ]; In patients with pHPT requiring surgery, preoperative localization of the hyperfunctioning gland(s) enables selective and focused parathyroidectomy. This approach may reduce operation time, minimize complications, improve postoperative recovery, enhance cosmetic outcomes and increase patient satisfaction [ 6 ]. Historically, the first line nuclear medicine imaging modality for parathyroid imaging has been [99mTc]Tc-MIBI due to the high concentration of mitochondria in the parathyroid neoplasms[ 6 ]. However emerging evidence demonstrates the superior diagnostic performance of [18F]Fluorocholine Positron Emission Tomography (PET) imaging in detecting parathyroid adenomas in patients with pHPT [ 7 ], offering greater diagnostic accuracy [ 8 ]. Consequently, [18F]Fluorocholine PET imaging is increasingly considered a viable alternative imaging method, whenever available. It has proven effective even in patients with negative or inconclusive findings from standard imaging methods such as [99mTc]Tc-MIBI scintigraphy [ 6 ]. Different hybrid PET/CT and PET/MR systems are on the market and used daily for clinical practice, with PET/CT being the most diffuse. Here, we present a 15-year-old male patient with pHPT, who was referred to our unit to perform a PET/CT with [18F]Fluorocholine to localize parathyroid glands and imaging results suggested a HPT-JT syndrome. Case Presentation A 15-year-old boy presented to a Nuclear Medicine unit of a hospital, to perform [18F]Fluorocholine PET/CT, following an in-patient procedure for hematuria. During the procedure blood tests revealed severe hypercalcemia, hypercalciuria and hyperparathormonemia. Additionally, the patient exhibited ventricular repolarization abnormalities on the EKG. Patient underwent neck echography which raised suspicion of an enlarged left inferior parathyroid gland. A neck MR confirmed the presence of a solitary nodular formation below the left thyroid lobe. A parathyroid scintigraphy with [99mTc] MIBI was performed afterward, but it was inconclusive. The familial history was negative for endocrine diseases; the patient underwent one year earlier a removal of a cemento-ossifying fibroma of the right maxilla. During the inpatient stay the patient autonomously expelled renal calculi. An abdomen and pelvic Ultrasound (US) procedure was performed, showing only urolithiasis, without any additional features of clinical relevance at the renal parenchyma and to the other abdominal and pelvic organs explored. The patient underwent a [18F] Fluorocholine PET/CT to plan neck surgery and to metabolically characterize and locate a suspected parathyroid neoplasm The images were acquired on a PET/CT scanner (Omni Legend, GE HealthCare) from the vertex to the mediastinum, revealing a nodular formation in the left caudal thyroid lobe with focal uptake strongly suggestive of a solitary parathyroid neoplasm. Additionally, [18F]Fluorocholine PET/CT demonstrated a diffused and intense uptake in the right maxilla, corresponding to a 17x22mm lesion. The CT features of this lesion suggested the presence of a recurrent ossifying jaw fibroma (Fig. 1 ). Following the PET/CT scan the patient underwent genetic testing for the CDC73 mutation which confirmed a diagnosis of hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Conclusions While [18F]FDG PET/CT and [11C]Methionine PET/CT have been reported in cases of HPT-JT syndrome [ 9 , 10 ], to the best of our knowledge this is the first case in literature reporting the use of [18F]Fluorocholine PET/CT in a patient with HPT-JT syndrome. The only previously reported case involving [18F]FDG PET/CT [ 9 ] described the imaging of a patient suspected for malignancy of the maxilla - afterwards classified as a cemento-ossifying fibroma – with a concomitant incidentally found parathyroid carcinoma. As outlined in the European Association of Nuclear Medicine (EANM) guidelines for parathyroid imaging, [18F]Fluorocholine is the radiopharmaceutical of choice for PET imaging in patients with pHPT for characterizing parathyroid lesions [ 6 ]; although [11C]Methionine has also been used for localizing parathyroid, a meta-analysis by Bioletto et al. [ 11 ] provided a quantitative evidence supporting the likely superiority of [18F]Fluorocholine over 11[C]Methionine in terms of sensitivity. Both tracers showed a high and comparable positive predictive value. Moreover, [11C]Methionine radiopharmaceutical requires an on-site cyclotron for its production and use, whereas [18F]Fluorocholine is commercially available and can be delivered to the site of use. Recently, Iacobone et al. reported a 95% rate of single-gland involvement in a cohort of 20 HPT-JT syndrome patients from five large families. Therefore, when preoperative imaging techniques concordantly localize a single-gland and there is no suspicion of parathyroid malignancy, a focused approach with selective parathyroidectomy has been proposed. Conversely, in case of absent or discordant preoperative localization, a bilateral neck exploration with subtotal parathyroidectomy is suggested due to the increased risk of multiglandular involvement, with persistent and recurrent pHPT in case of focused exploration [ 12 ]. Regardless of the surgical approach, according to a literature review, the risk of recurrence is estimated to be about 25%, necessitating regular lifelong pHPT biochemical and instrumental monitoring [ 2 , 3 ]. In our patient, given the absence of suspicious abdominal masses in the US, our PET/CT scan did not include the abdomen, considering the physiologic renal excretion of the radiopharmaceutical which reduces the study’s sensitivity in the renal parenchyma [ 13 ]. Even though the most common -and sometimes only- feature of HPT-JT is pHPT [ 3 ], jaw lesions may precede the development of hypercalcemia by years potentially leading to misdiagnosis [ 14 ]. In the case of our young patient using [18F]Fluorocholine PET/CT we were able to accurately localize the patient’s solitary parathyroid neoplasm and predicted valuable information for surgical planning. Additionally, we identified intense uptake indicative of a relapse or persistence of the known maxilla cemento-ossifying fibroma. Our study was also able to demonstrate the absence of further jaw cemento-ossifying fibroma. Current guidelines recommends that all CDC73 mutation carriers should undergo regular clinical and instrumental follow up. This includes biochemical evaluation of PTH and serum calcium levels, and period imaging studies such as neck ultrasound, orthopantomogram (OPG), renal and pelvic ultrasound, CT, or MR [ 2 , 4 ]. This case aims to promote awareness regarding the usefulness of advanced Nuclear Medicine techniques in the management and follow-up of the rare pathologic condition of HPT-JT syndrome and its various clinical associations. This case suggests that [18F]Fluorocholine PET/CT may be utilized in the management and follow up of HPT-JT patients given the high uptake observed in both parathyroid tumors and the cemento-ossifying fibromas. This case underlines the importance of a thorough patient history and a multidisciplinary approach in managing complex endocrine conditions. It also underscores the role of [18F]Fluorocholine PET/CT as a valuable tool for diagnosis, treatment planning, and follow-up in patients with HPT-JT syndrome. Abbreviations EANM – European Association of Nuclear Medicine EKG – Electrocardiogram FDG – Fluorodeoxyglucose FIHP – Familial Isolated Hyperparathyroidism HPT-JT – Hyperparathyroidism-jaw tumor MEN1 – Multiple Endocrine Neoplasia type 1 MEN2A – Multiple Endocrine Neoplasia type 2A MEN4 – Multiple Endocrine Neoplasia type 4 MR – Magnetic Resonance OPG – Orthopantomogram PET/CT – Positron Emission Tomography / Computed Tomography pHPT – Primary hyperparathyroidism PTH – Parathyroid Hormone [99mTc]Tc-MIBI – Technetium-99m methoxy-isobutyl-isonitrile US – Ultrasound Declarations Ethics approval and consent to participate This study was conducted in accordance with institutional and national ethical standards; a specific approval from our Institution Review Board was not required for this specific paper. The patient’s legal guardians provided written informed consent for participation in this case report. Consent for publication Written informed consent was obtained from the patient’s legal guardians for the publication of this case report and any accompanying images. Availability of data and material All relevant data analyzed during this study are included in this published article. Additional data supporting the findings of this study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding No specific funding was received for this work. Authors' contributions FS and DC contributed to the conceptualization and drafting of the manuscript. CL, FS and DC contributed to image analysis and interpretation. MI and FT reviewd the manuscript and contributed to the clinical discussion. All authors reviewed, edited, and approved the final manuscript. Acknowledgements Not applicable References Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein LS, Cochran C, et al. Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res Off J Am Soc Bone Miner Res. 2002;17 Suppl 2:N37-43. Iacobone M, Carnaille B, Palazzo FF, Vriens M. Hereditary hyperparathyroidism--a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2015 Dec;400(8):867-86. Masi G, Barzon L, Iacobone M, Viel G, Porzionato A, Macchi V, et al. Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer. 2008;15:1115–26. Torresan F, Iacobone M. Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature. Int J Endocrinol. 2019;2019:1761030. Kelly TG, Shattuck TM, Reyes-Mugica M, Stewart AF, Simonds WF, Udelsman R, et al. Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res Off J Am Soc Bone Miner Res. 2006;21:1666–71. Petranović Ovčariček P, Giovanella L, Carrió Gasset I, Hindié E, Huellner MW, Luster M, et al. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021;48:2801–22. Treglia G, Rizzo A, Piccardo A. Expanding the clinical indications of [18F]fluorocholine PET/CT in primary hyperparathyroidism: the evidence cannot be evaded. Eur J Nucl Med Mol Imaging. 2024;51:1345–8. Treglia G, Piccardo A, Paone G, Trimboli P, Imperiale A. [18F]Fluorocholine PET/CT as First-Line vs. Second-Line Imaging Method to localize parathyroid adenomas in primary hyperparathyroidism: “Game, Set, and Match.” Eur J Nucl Med Mol Imaging. 2024;51:3596–9. Nazerani Hooshmand T, Pernthaler B, Szurian K, Pau M, Aigner RM. 18F-FDG PET/CT in the Hyperparathyroidism-Jaw-Tumor Syndrome. Clin Nucl Med. 2021;46:497–8. Mele M, Rolighed L, Jespersen M, Rejnmark L, Christiansen P. Recurrence of Hyperparathyroid Hypercalcemia in a Patient With the HRPT-2 Mutation and a Previous Parathyroid Carcinoma in Hyperparathyroidism-Jaw Tumor Syndrome. Int J Endocrinol Metab. 2016;14:e35424. Bioletto F, Barale M, Parasiliti-Caprino M, Prencipe N, Berton AM, Procopio M, et al. Comparison of the diagnostic accuracy of 18F-Fluorocholine PET and 11C-Methionine PET for parathyroid localization in primary hyperparathyroidism: a systematic review and meta-analysis. Eur J Endocrinol. 2021;185:109–20. Iacobone M, Camozzi V, Mian C, Pennelli G, Pagetta C, Casal Ide E, et al. Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations. World J Surg. 2020;44:508–16. Calabria F, Chiaravalloti A, Cicciò C, Gangemi V, Gullà D, Rocca F, et al. PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience. Nucl Med Biol. 2017;51:40–54. Cavaco BM, Barros L, Pannett AAJ, Ruas L, Carvalheiro M, Ruas MMA, et al. The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred. QJM - Mon J Assoc Physicians. 2001;94:213–22. Cite Share Download PDF Status: Published Journal Publication published 14 Jan, 2026 Read the published version in EJNMMI Research → Version 1 posted Editorial decision: Major Revision 31 Mar, 2025 Reviewers agreed at journal 28 Mar, 2025 Reviewers invited by journal 28 Mar, 2025 Editor assigned by journal 19 Mar, 2025 First submitted to journal 17 Mar, 2025 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-6190034","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":435346916,"identity":"8d83c9dc-a1be-4eb4-a2f0-36d898439af2","order_by":0,"name":"Francesca Serani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBAC9gY0AR5+IHGAgY2BB5cWngPoApINUC249GBoYTAAi7Ax4LSGR/rwswc/Kurk+RvYHz6uqLkjY3wj9+DhgjIGGXtcWvjSzA17zhw2nHGAx9jwzLFnPGY38hIOzziH22H2PAxm0oxtBxIYDvCwSTawHQZqyTE4zNuGxy887N+kGf/VJcgfYH/+s+HfYR7jGQS18ABtaWBOAPrajLGx7TCPgQRhLWWSPccOG24Emi/Z2HeYR+LMGwOgXyR4MAMT7rBtEj9q6uTljrc//Njw7bA9f3uO8eeCMht7jFjGAMyobAlC6vFoHwWjYBSMglEAAL9mUEgz59KQAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-7470-0614","institution":"UNIPD DIMED: Universita degli Studi di Padova Dipartimento di Medicina","correspondingAuthor":true,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Serani","suffix":""},{"id":435346917,"identity":"8e9e223d-afcb-4a2d-9159-3a300da4cd70","order_by":1,"name":"Carmelo Salvino Lacognata","email":"","orcid":"","institution":"Azienda Ospedale Universita Padova","correspondingAuthor":false,"prefix":"","firstName":"Carmelo","middleName":"Salvino","lastName":"Lacognata","suffix":""},{"id":435346918,"identity":"894cd650-1011-473b-9528-758dfd3b7e5d","order_by":2,"name":"Francesca Torresan","email":"","orcid":"","institution":"Azienda Ospedale Universita Padova","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Torresan","suffix":""},{"id":435346919,"identity":"781d2b0f-6602-4ecc-89ce-4c7ea363ec8d","order_by":3,"name":"Maurizio Iacobone","email":"","orcid":"","institution":"Azienda Ospedale Universita Padova","correspondingAuthor":false,"prefix":"","firstName":"Maurizio","middleName":"","lastName":"Iacobone","suffix":""},{"id":435346920,"identity":"118be7d9-a956-4fd6-b2c5-0a9ed080567a","order_by":4,"name":"Diego Cecchin","email":"","orcid":"","institution":"UNIPD DIMED: Universita degli Studi di Padova Dipartimento di Medicina","correspondingAuthor":false,"prefix":"","firstName":"Diego","middleName":"","lastName":"Cecchin","suffix":""}],"badges":[],"createdAt":"2025-03-09 18:24:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6190034/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6190034/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13550-025-01267-x","type":"published","date":"2026-01-14T16:29:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80813544,"identity":"2002eead-beda-48e3-afb8-ad96e7751b1b","added_by":"auto","created_at":"2025-04-17 10:41:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":251490,"visible":true,"origin":"","legend":"\u003cp\u003eFirst column: Axial fused images of [18F]Choline PET/CT showing high uptake of the radiopharmaceutical corresponding to the ossifying fibroma visible on CT (second column). Third column: Fused [18F]Choline PET/CT showing high uptake (red arrows) in a solitary, oblong, left parathyroid tumor that presented a cystic portion on the medial portion (without significant uptake).\u003c/p\u003e","description":"","filename":"IMMAGINECASE.png","url":"https://assets-eu.researchsquare.com/files/rs-6190034/v1/b93f10478bad6cc080e7c7ad.png"},{"id":100616095,"identity":"9840b765-88d9-4b4a-8801-c5e9541f9925","added_by":"auto","created_at":"2026-01-19 17:39:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":565540,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6190034/v1/44ba6304-cd88-4b12-8663-c86c998a5cc5.pdf"}],"financialInterests":"","formattedTitle":"[18F]Fluorocholine PET/CT in a 15-Year-Old patient suggested HPT-JT Syndrome with Active Cemento-ossifying Fibroma","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary hyperparathyroidism (pHPT) is typically a sporadic disorder though it can be heritable in approximately 10% of cases; in this cases it can occur as an isolated condition or as part of a syndrome involving tumors in other tissues. Syndromes associated with pHPT include multiple endocrine neoplasia types 1 (MEN1), 2A (MEN2A) and 4 (MEN4), hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and familial isolated hyperparathyroidism (FIHP) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHPT-JT is a rare autosomal dominant disease with incomplete penetrance, caused by mutations in the suppressor gene CDC73 (formerly known as HRPT2), which encodes for parafibromin [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This inherited endocrine neoplastic syndrome predisposes individuals to a triad of conditions including multiple maxillary or mandibular cemento-ossifying fibromas, benign and malignant parathyroid neoplasms, cystic and neoplastic renal abnormalities, and hyperplastic and neoplastic uterine involvement [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the most common - and sometimes sole - manifestation of HPT-JT is pHPT [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. HPT-JT is more frequently associated with atypical adenomas and parathyroid carcinomas compared to other pHPT conditions [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNuclear medicine techniques are crucial in identifying and localizing hyperfunctioning parathyroid glands [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; In patients with pHPT requiring surgery, preoperative localization of the hyperfunctioning gland(s) enables selective and focused parathyroidectomy. This approach may reduce operation time, minimize complications, improve postoperative recovery, enhance cosmetic outcomes and increase patient satisfaction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorically, the first line nuclear medicine imaging modality for parathyroid imaging has been [99mTc]Tc-MIBI due to the high concentration of mitochondria in the parathyroid neoplasms[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However emerging evidence demonstrates the superior diagnostic performance of [18F]Fluorocholine Positron Emission Tomography (PET) imaging in detecting parathyroid adenomas in patients with pHPT [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], offering greater diagnostic accuracy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Consequently, [18F]Fluorocholine PET imaging is increasingly considered a viable alternative imaging method, whenever available. It has proven effective even in patients with negative or inconclusive findings from standard imaging methods such as [99mTc]Tc-MIBI scintigraphy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDifferent hybrid PET/CT and PET/MR systems are on the market and used daily for clinical practice, with PET/CT being the most diffuse.\u003c/p\u003e \u003cp\u003eHere, we present a 15-year-old male patient with pHPT, who was referred to our unit to perform a PET/CT with [18F]Fluorocholine to localize parathyroid glands and imaging results suggested a HPT-JT syndrome.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 15-year-old boy presented to a Nuclear Medicine unit of a hospital, to perform [18F]Fluorocholine PET/CT, following an in-patient procedure for hematuria. During the procedure blood tests revealed severe hypercalcemia, hypercalciuria and hyperparathormonemia. Additionally, the patient exhibited ventricular repolarization abnormalities on the EKG. Patient underwent neck echography which raised suspicion of an enlarged left inferior parathyroid gland.\u003c/p\u003e \u003cp\u003eA neck MR confirmed the presence of a solitary nodular formation below the left thyroid lobe. A parathyroid scintigraphy with [99mTc] MIBI was performed afterward, but it was inconclusive.\u003c/p\u003e \u003cp\u003eThe familial history was negative for endocrine diseases; the patient underwent one year earlier a removal of a cemento-ossifying fibroma of the right maxilla. During the inpatient stay the patient autonomously expelled renal calculi. An abdomen and pelvic Ultrasound (US) procedure was performed, showing only urolithiasis, without any additional features of clinical relevance at the renal parenchyma and to the other abdominal and pelvic organs explored.\u003c/p\u003e \u003cp\u003eThe patient underwent a [18F] Fluorocholine PET/CT to plan neck surgery and to metabolically characterize and locate a suspected parathyroid neoplasm The images were acquired on a PET/CT scanner (Omni Legend, GE HealthCare) from the vertex to the mediastinum, revealing a nodular formation in the left caudal thyroid lobe with focal uptake strongly suggestive of a solitary parathyroid neoplasm.\u003c/p\u003e \u003cp\u003eAdditionally, [18F]Fluorocholine PET/CT demonstrated a diffused and intense uptake in the right maxilla, corresponding to a 17x22mm lesion. The CT features of this lesion suggested the presence of a recurrent ossifying jaw fibroma (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFollowing the PET/CT scan the patient underwent genetic testing for the CDC73 mutation which confirmed a diagnosis of hyperparathyroidism-jaw tumor (HPT-JT) syndrome.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWhile [18F]FDG PET/CT and [11C]Methionine PET/CT have been reported in cases of HPT-JT syndrome [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], to the best of our knowledge this is the first case in literature reporting the use of [18F]Fluorocholine PET/CT in a patient with HPT-JT syndrome.\u003c/p\u003e \u003cp\u003eThe only previously reported case involving [18F]FDG PET/CT [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] described the imaging of a patient suspected for malignancy of the maxilla - afterwards classified as a cemento-ossifying fibroma \u0026ndash; with a concomitant incidentally found parathyroid carcinoma.\u003c/p\u003e \u003cp\u003eAs outlined in the European Association of Nuclear Medicine (EANM) guidelines for parathyroid imaging, [18F]Fluorocholine is the radiopharmaceutical of choice for PET imaging in patients with pHPT for characterizing parathyroid lesions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; although [11C]Methionine has also been used for localizing parathyroid, a meta-analysis by Bioletto et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] provided a quantitative evidence supporting the likely superiority of [18F]Fluorocholine over 11[C]Methionine in terms of sensitivity. Both tracers showed a high and comparable positive predictive value. Moreover, [11C]Methionine radiopharmaceutical requires an on-site cyclotron for its production and use, whereas [18F]Fluorocholine is commercially available and can be delivered to the site of use.\u003c/p\u003e \u003cp\u003eRecently, Iacobone et al. reported a 95% rate of single-gland involvement in a cohort of 20 HPT-JT syndrome patients from five large families. Therefore, when preoperative imaging techniques concordantly localize a single-gland and there is no suspicion of parathyroid malignancy, a focused approach with selective parathyroidectomy has been proposed. Conversely, in case of absent or discordant preoperative localization, a bilateral neck exploration with subtotal parathyroidectomy is suggested due to the increased risk of multiglandular involvement, with persistent and recurrent pHPT in case of focused exploration [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Regardless of the surgical approach, according to a literature review, the risk of recurrence is estimated to be about 25%, necessitating regular lifelong pHPT biochemical and instrumental monitoring [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our patient, given the absence of suspicious abdominal masses in the US, our PET/CT scan did not include the abdomen, considering the physiologic renal excretion of the radiopharmaceutical which reduces the study\u0026rsquo;s sensitivity in the renal parenchyma [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEven though the most common -and sometimes only- feature of HPT-JT is pHPT [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], jaw lesions may precede the development of hypercalcemia by years potentially leading to misdiagnosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the case of our young patient using [18F]Fluorocholine PET/CT we were able to accurately localize the patient\u0026rsquo;s solitary parathyroid neoplasm and predicted valuable information for surgical planning. Additionally, we identified intense uptake indicative of a relapse or persistence of the known maxilla cemento-ossifying fibroma. Our study was also able to demonstrate the absence of further jaw cemento-ossifying fibroma.\u003c/p\u003e \u003cp\u003eCurrent guidelines recommends that all CDC73 mutation carriers should undergo regular clinical and instrumental follow up. This includes biochemical evaluation of PTH and serum calcium levels, and period imaging studies such as neck ultrasound, orthopantomogram (OPG), renal and pelvic ultrasound, CT, or MR [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case aims to promote awareness regarding the usefulness of advanced Nuclear Medicine techniques in the management and follow-up of the rare pathologic condition of HPT-JT syndrome and its various clinical associations. This case suggests that [18F]Fluorocholine PET/CT may be utilized in the management and follow up of HPT-JT patients given the high uptake observed in both parathyroid tumors and the cemento-ossifying fibromas.\u003c/p\u003e \u003cp\u003eThis case underlines the importance of a thorough patient history and a multidisciplinary approach in managing complex endocrine conditions. It also underscores the role of [18F]Fluorocholine PET/CT as a valuable tool for diagnosis, treatment planning, and follow-up in patients with HPT-JT syndrome.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEANM \u0026ndash; European Association of Nuclear Medicine\u003c/p\u003e\n\u003cp\u003eEKG \u0026ndash; Electrocardiogram\u003c/p\u003e\n\u003cp\u003eFDG \u0026ndash; Fluorodeoxyglucose\u003c/p\u003e\n\u003cp\u003eFIHP \u0026ndash; Familial Isolated Hyperparathyroidism\u003c/p\u003e\n\u003cp\u003eHPT-JT \u0026ndash; Hyperparathyroidism-jaw tumor\u003c/p\u003e\n\u003cp\u003eMEN1 \u0026ndash; Multiple Endocrine Neoplasia type 1\u003c/p\u003e\n\u003cp\u003eMEN2A \u0026ndash; Multiple Endocrine Neoplasia type 2A\u003c/p\u003e\n\u003cp\u003eMEN4 \u0026ndash; Multiple Endocrine Neoplasia type 4\u003c/p\u003e\n\u003cp\u003eMR \u0026ndash; Magnetic Resonance\u003c/p\u003e\n\u003cp\u003eOPG \u0026ndash; Orthopantomogram\u003c/p\u003e\n\u003cp\u003ePET/CT \u0026ndash; Positron Emission Tomography / Computed Tomography\u003c/p\u003e\n\u003cp\u003epHPT \u0026ndash; Primary hyperparathyroidism\u003c/p\u003e\n\u003cp\u003ePTH \u0026ndash; Parathyroid Hormone\u003c/p\u003e\n\u003cp\u003e[99mTc]Tc-MIBI \u0026ndash; Technetium-99m methoxy-isobutyl-isonitrile\u003c/p\u003e\n\u003cp\u003eUS \u0026ndash; Ultrasound\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with institutional and national ethical standards; a specific approval from our Institution Review Board was not required for this specific paper. The patient\u0026rsquo;s legal guardians provided written informed consent for participation in this case report.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s legal guardians for the publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material\u003c/p\u003e\n\u003cp\u003eAll relevant data analyzed during this study are included in this published article. Additional data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Funding\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this work.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eFS and DC contributed to the conceptualization and drafting of the manuscript. CL, FS and DC contributed to image analysis and interpretation. MI and FT reviewd the manuscript and contributed to the clinical discussion. All authors reviewed, edited, and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMarx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein LS, Cochran C, et al. Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res Off J Am Soc Bone Miner Res. 2002;17 Suppl 2:N37-43. \u003c/li\u003e\n\u003cli\u003eIacobone M, Carnaille B, Palazzo FF, Vriens M. Hereditary hyperparathyroidism--a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2015 Dec;400(8):867-86.\u003c/li\u003e\n\u003cli\u003eMasi G, Barzon L, Iacobone M, Viel G, Porzionato A, Macchi V, et al. Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer. 2008;15:1115\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eTorresan F, Iacobone M. Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature. Int J Endocrinol. 2019;2019:1761030. \u003c/li\u003e\n\u003cli\u003eKelly TG, Shattuck TM, Reyes-Mugica M, Stewart AF, Simonds WF, Udelsman R, et al. Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res Off J Am Soc Bone Miner Res. 2006;21:1666\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003ePetranović Ovčariček P, Giovanella L, Carri\u0026oacute; Gasset I, Hindi\u0026eacute; E, Huellner MW, Luster M, et al. The EANM practice guidelines for parathyroid imaging. Eur J Nucl Med Mol Imaging. 2021;48:2801\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eTreglia G, Rizzo A, Piccardo A. Expanding the clinical indications of [18F]fluorocholine PET/CT in primary hyperparathyroidism: the evidence cannot be evaded. Eur J Nucl Med Mol Imaging. 2024;51:1345\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eTreglia G, Piccardo A, Paone G, Trimboli P, Imperiale A. [18F]Fluorocholine PET/CT as First-Line vs. Second-Line Imaging Method to localize parathyroid adenomas in primary hyperparathyroidism: \u0026ldquo;Game, Set, and Match.\u0026rdquo; Eur J Nucl Med Mol Imaging. 2024;51:3596\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eNazerani Hooshmand T, Pernthaler B, Szurian K, Pau M, Aigner RM. 18F-FDG PET/CT in the Hyperparathyroidism-Jaw-Tumor Syndrome. Clin Nucl Med. 2021;46:497\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eMele M, Rolighed L, Jespersen M, Rejnmark L, Christiansen P. Recurrence of Hyperparathyroid Hypercalcemia in a Patient With the HRPT-2 Mutation and a Previous Parathyroid Carcinoma in Hyperparathyroidism-Jaw Tumor Syndrome. Int J Endocrinol Metab. 2016;14:e35424. \u003c/li\u003e\n\u003cli\u003eBioletto F, Barale M, Parasiliti-Caprino M, Prencipe N, Berton AM, Procopio M, et al. Comparison of the diagnostic accuracy of 18F-Fluorocholine PET and 11C-Methionine PET for parathyroid localization in primary hyperparathyroidism: a systematic review and meta-analysis. Eur J Endocrinol. 2021;185:109\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eIacobone M, Camozzi V, Mian C, Pennelli G, Pagetta C, Casal Ide E, et al. Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations. World J Surg. 2020;44:508\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eCalabria F, Chiaravalloti A, Cicci\u0026ograve; C, Gangemi V, Gull\u0026agrave; D, Rocca F, et al. PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience. Nucl Med Biol. 2017;51:40\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eCavaco BM, Barros L, Pannett AAJ, Ruas L, Carvalheiro M, Ruas MMA, et al. The hyperparathyroidism-jaw tumour syndrome in a Portuguese kindred. QJM - Mon J Assoc Physicians. 2001;94:213\u0026ndash;22. \u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejre","sideBox":"Learn more about [EJNMMI Research](http://ejnmmires.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejre/default.aspx","title":"EJNMMI Research","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6190034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6190034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant disorder caused by CDC73 gene mutations, predisposing individuals to primary hyperparathyroidism (pHPT), cemento-ossifying fibromas, and other neoplastic conditions. [18F]Fluorocholine PET/CT has emerged as a tool for localizing hyperfunctioning parathyroid glands in pHPT, but its application in HPT-JT syndrome remains unreported.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eWe describe the case of a 15-year-old male presenting with severe hypercalcemia, hyperparathormonemia, and a history of cemento-ossifying fibroma removal. Standard imaging, including [99mTc]Tc-MIBI scintigraphy, was inconclusive. [18F]Fluorocholine PET/CT successfully identified a hyperfunctioning parathyroid neoplasm and a recurrent maxillary cemento-ossifying fibroma. Genetic testing confirmed a CDC73 mutation, leading to the diagnosis of HPT-JT syndrome.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTo our knowledge, this is the first reported case utilizing [18F]Fluorocholine PET/CT for the diagnosis and management of HPT-JT syndrome. Given its superior sensitivity compared to conventional imaging, [18F]Fluorocholine PET/CT provided critical information for surgical planning and long-term disease monitoring. This case highlights the potential role of [18F]Fluorocholine PET/CT in detecting both parathyroid and maxillary manifestations of HPT-JT syndrome, emphasizing the need for further research into its application in hereditary endocrine disorders.\u003c/p\u003e","manuscriptTitle":"[18F]Fluorocholine PET/CT in a 15-Year-Old patient suggested HPT-JT Syndrome with Active Cemento-ossifying Fibroma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 10:41:17","doi":"10.21203/rs.3.rs-6190034/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2025-03-31T11:52:12+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-03-28T13:04:13+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-28T12:37:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-20T01:52:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"EJNMMI Research","date":"2025-03-17T18:02:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ejnmmi-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejre","sideBox":"Learn more about [EJNMMI Research](http://ejnmmires.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejre/default.aspx","title":"EJNMMI Research","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bcc2523d-987e-4c84-ba44-3707794d0665","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T17:04:59+00:00","versionOfRecord":{"articleIdentity":"rs-6190034","link":"https://doi.org/10.1186/s13550-025-01267-x","journal":{"identity":"ejnmmi-research","isVorOnly":false,"title":"EJNMMI Research"},"publishedOn":"2026-01-14 16:29:58","publishedOnDateReadable":"January 14th, 2026"},"versionCreatedAt":"2025-04-17 10:41:17","video":"","vorDoi":"10.1186/s13550-025-01267-x","vorDoiUrl":"https://doi.org/10.1186/s13550-025-01267-x","workflowStages":[]},"version":"v1","identity":"rs-6190034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6190034","identity":"rs-6190034","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}