Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097, Halle (Saale), Germany.
Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
Endocrine. 2023 Apr;80(1):100-110. doi: 10.1007/s12020-022-03273-8. Epub 2022 Dec 2.
Thirty years into the genomic era, this study sought to explore events that helped transform the clinical landscape of hereditary medullary thyroid cancer (MTC).
This retrospective analysis of prospectively collected data included all RET carriers referred to a tertiary center for neck surgery that was performed between 1986 and 2021, using descriptive statistics and Poisson regression analysis.
Altogether, 496 RET carriers were referred for thyroidectomy (388 carriers) or neck reoperation (108 carriers). Of these, 44 carriers had highest risk mutations (p.Met918Thr), 164 carriers high risk mutations (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr/insHisGluLeuCys), 116 carriers moderate-high risk mutations (p.Cys609/611/618/620/630Arg/Gly/Phe/Ser/Tyr) and 172 carriers low-moderate risk mutations (p.Glu768Asp, p.Leu790Phe, p.Val804Leu/Met, or p.Ser891Ala). Three event clusters drove referral numbers upward: a string of first reports of causative RET mutations between 1993 and 1998; the international consensus guidelines for diagnosis and therapy of MEN type 1 and type 2 in 2001; and the revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma in 2015. Referrals for neck reoperation declined sluggishly over 30 years, ending in 2018. Index patients continued to be referred into 2021. Referrals for thyroidectomy, grouped in 5-year increments, peaked in 1996-2000 for carriers of highest and high risk mutations, and in 2006-2010 for carriers of moderate-high and low-moderate risk mutations, some 10 years later.
International management guidelines are critical in building and increasing the pressure towards screening of sporadic-appearing disease and offspring of known gene families by encompassing the complete disease spectrum early on.
在基因组时代的 30 年后，本研究旨在探索有助于改变遗传性髓样甲状腺癌（MTC）临床格局的事件。
本研究对前瞻性收集的数据进行回顾性分析，纳入了 1986 年至 2021 年间转诊至三级中心进行颈部手术的所有 RET 携带者，采用描述性统计和泊松回归分析。
共有 496 名 RET 携带者被转诊行甲状腺切除术（388 名携带者）或颈部再次手术（108 名携带者）。其中，44 名携带者携带最高风险突变（p.Met918Thr），164 名携带者携带高风险突变（p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr/insHisGluLeuCys），116 名携带者携带中高风险突变（p.Cys609/611/618/620/630Arg/Gly/Phe/Ser/Tyr），172 名携带者携带低中风险突变（p.Glu768Asp、p.Leu790Phe、p.Val804Leu/Met 或 p.Ser891Ala）。三个事件集群导致转诊人数上升：1993 年至 1998 年间连续报告的一系列 RET 致病突变；2001 年 MEN 1 型和 2 型的国际诊断和治疗共识指南；以及 2015 年修订的美国甲状腺协会 MTC 管理指南。30 年来，颈部再次手术的转诊数量缓慢下降，直到 2018 年结束。索引患者仍持续转诊至 2021 年。5 年为一组的甲状腺切除术转诊数量在携带最高和高风险突变的患者中于 1996-2000 年达到峰值，在携带中高和低中风险突变的患者中于 2006-2010 年达到峰值，比这晚了约 10 年。
国际管理指南在早期涵盖整个疾病谱的情况下，对于建立和增加对散发性疾病和已知基因突变家族后代的筛查压力至关重要。
