{"doi":"10.1210/jcemcr/luaf002","title":"Medullary Thyroid Carcinoma and Clinical Outcomes in Heterozygous Carriers of the <i>RET</i> K666N Germline Pathogenic Variant","abstract":"Abstract 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.","journal":"JCEM Case Reports","year":2025,"id":551717,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437901,"name":"Teresa Kim","orcid":"0000-0003-1404-0479","position":1,"is_corresponding":false},{"id":1339254,"name":"Esther Peluso","orcid":null,"position":2,"is_corresponding":false},{"id":225877,"name":"Steven E. Jacobsen","orcid":"0000-0001-9483-138X","position":3,"is_corresponding":false},{"id":698317,"name":"Michael W. Yeh","orcid":"0000-0001-7907-4245","position":4,"is_corresponding":false},{"id":748461,"name":"Melissa G. Lechner","orcid":"0000-0002-4744-6566","position":5,"is_corresponding":false},{"id":1448051,"name":"Allison T Yip","orcid":null,"position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:29.318076Z","pmid":"39963300","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}