{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:08:16Z","timestamp":1789546096039,"version":"build-2803163510"},"reference-count":14,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant hereditary endocrine tumor syndrome classically associated with medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism. Early recognition is important because cascade screening may identify affected relatives before advanced disease develops. We report a Syrian family with a clinically MEN2A-consistent phenotype. The index patient, a 37-year-old male, presented with a large multinodular thyroid mass and was found to have markedly elevated plasma metanephrines, bilateral adrenal masses, and elevated serum calcitonin and carcinoembryonic antigen. He underwent bilateral adrenalectomy followed by total thyroidectomy with bilateral neck dissection. Histopathology confirmed bilateral pheochromocytoma and multifocal MTC with gross extrathyroidal extension and lateral cervical lymph-node metastasis. Phenotype-driven cascade screening identified a 39-year-old sister with elevated calcitonin, metanephrine, and normetanephrine levels, bilateral adrenal masses, bilateral pheochromocytoma, and MTC, representing a second first-degree relative with the MEN2A-defining combination of MTC and bilateral pheochromocytoma. A 26-year-old brother was found to have synchronous papillary thyroid carcinoma and oncocytic\/H\u00fcrthle-cell carcinoma with negative calcitonin immunostaining. This family highlights the value of phenotype-driven cascade screening when rearranged during transfection (RET) proto-oncogene testing is unavailable and emphasizes the importance of precise pathological classification of nonmedullary thyroid tumors in individuals from MEN2A-consistent families.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag278","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:13:36Z","timestamp":1788520416000},"source":"Crossref","is-referenced-by-count":0,"title":["Phenotype-driven cascade screening in a Syrian family with clinically consistent multiple endocrine neoplasia type 2A"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-8709","authenticated-orcid":false,"given":"Munawar","family":"Hraib","sequence":"first","affiliation":[{"name":"Department of Oncology, Al-Bairuni University Hospital , Damascus ,","place":["Syria"]},{"name":"Faculty of Medicine, Damascus University , Damascus ,","place":["Syria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Alturun","sequence":"additional","affiliation":[{"name":"Department of Oncology, Al-Bairuni University Hospital , Damascus ,","place":["Syria"]},{"name":"Faculty of Medicine, Damascus University , Damascus ,","place":["Syria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6689-5632","authenticated-orcid":false,"given":"Taim","family":"Al Kheder","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Damascus University , Damascus ,","place":["Syria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faozat","family":"Alonainy","sequence":"additional","affiliation":[{"name":"Department of Oncology, Al-Bairuni University Hospital , Damascus ,","place":["Syria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026091603531192400_luag278-B1","first-page":"1993","volume-title":"GeneReviews(\u00ae)","author":"Eng","year":"1999"},{"key":"2026091603531192400_luag278-B2","volume-title":"Multiple Endocrine Neoplasias Type 2","author":"Lath"},{"key":"2026091603531192400_luag278-B3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.semcancer.2021.03.035","article-title":"Multiple endocrine neoplasia type 2: a review","volume":"79","author":"Mathiesen","year":"2022","journal-title":"Semin Cancer Biol"},{"issue":"6","key":"2026091603531192400_luag278-B4","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/thy.2014.0335","article-title":"Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma","volume":"25","author":"Wells","year":"2015","journal-title":"Thyroid"},{"issue":"3","key":"2026091603531192400_luag278-B5","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s12020-020-02332-2","article-title":"MEN2-related pheochromocytoma: current state of knowledge, specific characteristics in MEN2B, and perspectives","volume":"69","author":"Amodru","year":"2020","journal-title":"Endocrine"},{"issue":"1","key":"2026091603531192400_luag278-B6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO classification of thyroid neoplasms","volume":"33","author":"Baloch","year":"2022","journal-title":"Endocr Pathol"},{"issue":"5","key":"2026091603531192400_luag278-B7","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3803\/EnM.2022.1553","article-title":"Update from the 2022 World Health Organization classification of thyroid tumors: a standardized diagnostic approach","volume":"37","author":"Jung","year":"2022","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"6","key":"2026091603531192400_luag278-B8","first-page":"1059","article-title":"Expression of papillary thyroid carcinoma in multiple endocrine neoplasia type 2A","volume":"114","author":"Decker","year":"1993","journal-title":"Surgery"},{"issue":"11","key":"2026091603531192400_luag278-B9","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s40618-015-0290-y","article-title":"Papillary thyroid carcinoma and multiple endocrine neoplasia type 2","volume":"38","author":"Febrero","year":"2015","journal-title":"J Endocrinol Invest"},{"issue":"1","key":"2026091603531192400_luag278-B10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/030089160709300121","article-title":"Simultaneous occurrence of medullary carcinoma and papillary microcarcinoma of thyroid in a patient with MEN 2A syndrome. Report of a case","volume":"93","author":"Giacomelli","year":"2007","journal-title":"Tumori"},{"issue":"10","key":"2026091603531192400_luag278-B11","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11101516","article-title":"Epidemiology of simultaneous medullary and papillary thyroid carcinomas (MTC\/PTC): an Italian multicenter study","volume":"11","author":"Appetecchia","year":"2019","journal-title":"Cancers (Basel)"},{"issue":"5","key":"2026091603531192400_luag278-B12","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2022-248879","article-title":"Synchronous H\u00fcrthle cell and medullary thyroid carcinomas","volume":"15","author":"Yeap","year":"31 2022","journal-title":"BMJ Case Rep"},{"issue":"1","key":"2026091603531192400_luag278-B13","first-page":"83","article-title":"Oncocytic variant of medullary thyroid carcinoma\u2014a case report","volume":"14","author":"Parampalli Srinivas","year":"2019","journal-title":"Iran J Pathol"},{"issue":"5","key":"2026091603531192400_luag278-B14","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1177\/10668969251415524","article-title":"Rare RET variants in a patient with MEN2A and multiple follicular-derived thyroid tumors: a case report and review of the literature","volume":"34","author":"Song","year":"2026","journal-title":"Int J Surg Pathol"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/10\/luag278\/71115241\/luag278.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/4\/10\/luag278\/71115241\/luag278.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:53:19Z","timestamp":1789545199000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luag278\/8800985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":14,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luag278","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,9,3]]},"article-number":"luag278"}}