{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:45:50Z","timestamp":1760132750648,"version":"3.41.2"},"reference-count":13,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["K08DK129829"],"award-info":[{"award-number":["K08DK129829"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of the thyroid parafollicular C-cells associated with activating mutations in the rearranged during transfection (RET) kinase proto-oncogene. We report the clinical outcomes of a family with a rare germline RET K666N pathogenic variant discovered incidentally by genetic testing performed for breast cancer risk stratification in an asymptomatic 24-year-old woman. Subsequent genetic testing identified the same pathogenic variant in her 21-year-old sister, 60-year-old father, and 84-year-old paternal grandmother. The proband and her sister had no biochemical or imaging evidence of MTC. The 60-year-old father had mildly elevated serum calcitonin and multiple thyroid nodules on ultrasound. Fine-needle aspirate thyroid biopsy cytology suggested MTC so he underwent total thyroidectomy. Surgical pathology demonstrated bilateral subcentimeter foci of MTC and C-cell hyperplasia. The 84-year-old grandmother was also found to have multiple thyroid nodules and elevated calcitonin but declined further evaluation. There was no biochemical evidence of other multiple endocrine neoplastic type 2 (MEN2)-associated tumors (ie, parathyroid adenoma, pheochromocytoma) in the family. These data, along with prior rare reports in the literature, suggest that monoallelic germline RET K666N pathogenic variants carry a risk of familial MTC that demonstrate age-dependent expressivity but low penetrance of other MEN2 tumors in affected individuals.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf002","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:40:24Z","timestamp":1739785224000},"source":"Crossref","is-referenced-by-count":1,"title":["Medullary Thyroid Carcinoma and Clinical Outcomes in Heterozygous Carriers of the <i>RET<\/i> K666N Germline Pathogenic Variant"],"prefix":"10.1210","volume":"3","author":[{"given":"Allison T","family":"Yip","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, UCLA David Geffen School of Medicine , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa H","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, UCLA David Geffen School of Medicine , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther M","family":"Peluso","sequence":"additional","affiliation":[{"name":"UCLA\/Caltech Medical Scientist Training Program , UCLA Geffen School of Medicine, Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Developmental Biology, UCLA , Los Angeles, CA 90095 ,","place":["USA"]},{"name":"Howard Hughes Medical Institute, University of California, Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7907-4245","authenticated-orcid":false,"given":"Michael W","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, UCLA David Geffen School of Medicine , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-6566","authenticated-orcid":false,"given":"Melissa G","family":"Lechner","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, UCLA David Geffen School of Medicine , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"issue":"5","key":"2025021712070790800_luaf002-B1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1210\/endrev\/bnad013","article-title":"Medullary thyroid cancer: updates and challenges","volume":"44","author":"Gild","year":"2023","journal-title":"Endocr 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