Department of General, Visceral, and Vascular Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle (Saale), Germany.
J Clin Endocrinol Metab. 2013 Feb;98(2):E336-45. doi: 10.1210/jc.2012-3192. Epub 2013 Jan 2.
In multiple endocrine neoplasia type 2, American Thyroid Association (ATA) management guidelines recommend continuous biochemical screening for pheochromocytoma and/or primary hyperparathyroidism. This implicit assumption of linear tumor development is difficult to reconcile with current thinking that cells accrue somatic mutations stochastically, yielding a bell-shaped distribution.
This investigation aimed at evaluating the age distribution of pheochromocytoma and primary hyperparathyroidism in gene carriers at risk of developing multiple endocrine neoplasia type 2.
ATA class D, C, B, and A mutations, with or without pheochromocytoma and/or primary hyperparathyroidism, were plotted against carrier age at the time of diagnosis or last follow-up.
The setting was a surgical referral center.
Included were 474 carriers of ATA class D (37 patients), C (170 patients), B (112 patients), and A (155 patients) mutations. Eighty-four carriers (17.8%) developed pheochromocytoma (bilateral in 42 patients) and 20 carriers (4.2%) primary hyperparathyroidism.
INTERVENTIONS were adrenalectomy and/or parathyroidectomy.
Main outcome measures were multiple endocrine neoplasia type 2-associated tumors.
Bell-shaped age distribution curves were obtained for unilateral and bilateral pheochromocytoma (ATA class D, C, and B) and primary hyperparathyroidism (ATA class C and B). Owing to the rarity of events, the bell shape of the distribution curve was faint but consistent with a random distribution for ATA class A mutations (unilateral pheochromocytoma and primary hyperparathyroidism). With decreasing penetrance, the bell-shaped distribution curve, becoming narrower and flatter, shifted to the right toward higher age groups.
These data, revealing phases of greater amidst phases of lower penetrance, support adjustment of biochemical screening to carrier age and ATA class.
在 2 型多发性内分泌肿瘤中，美国甲状腺协会（ATA）管理指南建议对嗜铬细胞瘤和/或原发性甲状旁腺功能亢进症进行持续的生化筛查。这种线性肿瘤发展的隐含假设与当前的观点难以调和，当前的观点认为细胞随机获得体细胞突变，产生钟形分布。
本研究旨在评估有 2 型多发性内分泌肿瘤发病风险的基因携带者中嗜铬细胞瘤和原发性甲状旁腺功能亢进症的年龄分布。
ATA 分类 D、C、B 和 A 突变，无论是否伴有嗜铬细胞瘤和/或原发性甲状旁腺功能亢进症，均与诊断或最后一次随访时的携带者年龄相对应。
外科转诊中心。
共纳入 474 名携带 ATA 分类 D（37 例）、C（170 例）、B（112 例）和 A（155 例）突变的携带者。84 名携带者（17.8%）发生嗜铬细胞瘤（42 例为双侧），20 名携带者（4.2%）发生原发性甲状旁腺功能亢进症。
干预措施包括肾上腺切除术和/或甲状旁腺切除术。
主要观察指标为 2 型多发性内分泌肿瘤相关肿瘤。
获得了单侧和双侧嗜铬细胞瘤（ATA 分类 D、C 和 B）和原发性甲状旁腺功能亢进症（ATA 分类 C 和 B）的钟形年龄分布曲线。由于事件的罕见性，分布曲线的钟形形状微弱，但与 ATA 分类 A 突变（单侧嗜铬细胞瘤和原发性甲状旁腺功能亢进症）的随机分布一致。随着外显率的降低，钟形分布曲线变窄变平，向高龄组偏移。
这些数据显示出较高的穿透阶段和较低的穿透阶段，支持根据携带者年龄和 ATA 分类调整生化筛查。
