Loss of heterozygosity and absence of MAX immunostaining in a prolactinoma associated with multiple endocrine neoplasia type 5 (MEN5)

Loss of heterozygosity and absence of MAX immunostaining in a prolactinoma associated with multiple endocrine neoplasia type 5 (MEN5) | 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 Short Report Loss of heterozygosity and absence of MAX immunostaining in a prolactinoma associated with multiple endocrine neoplasia type 5 (MEN5) Brigitte Delemer, Simona M. Florea, Benedicte Decoudier, Camille Boulagnon-Rombi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7760856/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Nov, 2025 Read the published version in Pituitary → Version 2 posted 8 You are reading this latest preprint version Show more versions Abstract Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome caused by germline pathogenic variants involving the MYC Associated Factor X (MAX) gene. Affected individuals typically have pheochromocytomas, often bilateral, at a relatively early age. In MAX pheochromocytoma cohorts, pituitary adenomas are rarely reported. The role of MAX as a tumor suppressor gene in the pituitary gland has not been directly proven to date. The propositus came from a pheochromocytoma kindred with a germline pathogenic MAX variant c.97C>T (p.R33*). In his late thirties he developed asynchronous bilateral pheochromocytomas and underwent bilateral adrenalectomy. At age 46, he developed hyperprolactinemia (45.1 g/L; 3x ULN) and increased IGF-1 (460 ng/mL; 1.9x ULN). Total testosterone was low (1.5 ng/mL) as was LH (1.2 IU/L). Pituitary MRI showed a microadenoma (6 mm), which was resected and his prolactin, IGF-1, and testosterone levels normalized. A pituitary adenoma was confirmed on pathology, which showed positivity for prolactin only and a Ki67 of 2%. MAX immunohistochemical staining was lost in the pituitary adenoma cells. Tumoral DNA analysis (120X read depth) showed that at the MAX locus the pathogenic variant c.97C>T constituted >90% of the sequencing reads supporting tumoral loss of heterozygosity (LOH). Loss of MAX staining and the identification of tumor LOH at the MAX locus confirms pituitary adenomas as a component tumor in the emerging MEN5 syndrome due to germline pathogenic MAX variants. pituitary adenoma MEN5 pheochromocytoma genetics MAX Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Nov, 2025 Read the published version in Pituitary → Version 2 posted Editorial decision: Revision requested 27 Oct, 2025 Reviews received at journal 27 Oct, 2025 Reviewers agreed at journal 19 Oct, 2025 Reviews received at journal 19 Oct, 2025 Reviewers agreed at journal 19 Oct, 2025 Reviewers invited by journal 18 Oct, 2025 Submission checks completed at journal 18 Oct, 2025 First submitted to journal 17 Oct, 2025 You are reading this latest preprint version Show more versions 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. 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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-7760856","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":535892298,"identity":"45b8168a-d27b-44f7-9d51-4a77730351e6","order_by":0,"name":"Brigitte Delemer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3QsQrCMBCA4cvkEnGN6CsIJ4WoIPoqlUKnoqujxcFFcdUXyeRwJaBLxbWjLs46CorWDgoiUTeH/EMIBx9cAmCz/WEILqP7pQA8G2Tn4QOBjBQHT8JmXxEk/hiaSS3nER2DZs9ZrZeCLZrlypTYsG8gjfHejebKb6i46wvY+1wmLgtj02JJgDqvNMqEy9KZdEogtxsYSe+gL+qKzoxLAXTlckMsNJMANFOEKDJCXJJrJulbMJooD0UcOHUgL12sExpJ+mO77Um1sDCKqwlQqy03OjKSd7Ffgc1ms9leuwHl91KujOGG5wAAAABJRU5ErkJggg==","orcid":"","institution":"Centre Hospitalier Universitaire de Reims, Hôpital Robert-Debré","correspondingAuthor":true,"prefix":"","firstName":"Brigitte","middleName":"","lastName":"Delemer","suffix":""},{"id":535892299,"identity":"72a4cae3-a725-4e9e-af6b-bcab7424a54a","order_by":1,"name":"Simona M. 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Affected individuals typically have pheochromocytomas, often bilateral, at a relatively early age. In MAX pheochromocytoma cohorts, pituitary adenomas are rarely reported. The role of MAX as a tumor suppressor gene in the pituitary gland has not been directly proven to date.\nThe propositus came from a pheochromocytoma kindred with a germline pathogenic MAX variant c.97C\u003eT (p.R33*). In his late thirties he developed asynchronous bilateral pheochromocytomas and underwent bilateral adrenalectomy. At age 46, he developed hyperprolactinemia (45.1 g/L; 3x ULN) and increased IGF-1 (460 ng/mL; 1.9x ULN). Total testosterone was low (1.5 ng/mL) as was LH (1.2 IU/L). Pituitary MRI showed a microadenoma (6 mm), which was resected and his prolactin, IGF-1, and testosterone levels normalized. A pituitary adenoma was confirmed on pathology, which showed positivity for prolactin only and a Ki67 of 2%. MAX immunohistochemical staining was lost in the pituitary adenoma cells. 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