Machens Andreas, Elwerr Malik, Lorenz Kerstin, Weber Frank, Dralle Henning
Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097, Halle (Saale), Germany.
Department of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University of Duisburg-Essen, D-45122, Essen, Germany.
Endocrine. 2020 May;68(2):368-376. doi: 10.1007/s12020-020-02232-5. Epub 2020 Feb 25.
To determine whether published disease penetrance estimates of 50% for pheochromocytoma and 20-30% for primary hyperparathyroidism in multiple endocrine neoplasia (MEN 2A), conceivably reflecting overrepresentation of index patients with completely developed MEN 2A, may be too high.
Cross-sectional study of carriers at high risk of MEN 2A from a tertiary referral center.
There were 213 carriers of RET mutations in codon 634, born between 1922 and 2014. Median age of thyroidectomy was 17 years, with MTC being present in 76.5%; pheochromocytoma in 31.0% at a median of 34 years in the first, and in 18.8% at a median of 35 years in the second adrenal; and primary hyperparathyroidism in 10.8% at a median of 39 years. MTC, pheochromocytoma and primary hyperparathyroidism, stratified by year of birth, were diagnosed earlier over time: for MTC from 51 to 4 years; for pheochromocytoma from 51 to 22.5 years in the first, and from 51 to 29.5 years in the second adrenal, and for primary hyperparathyroidism from 46 to 12 years (P ≤ 0.008). This decline in age was paralleled by diminishing tumor diameters, more strongly in the thyroid (from 20 to 1.8 mm; P < 0.001) than in the adrenals (from 43 to 30 mm in the first, and from 20-57.5 to 30.5 mm in the second adrenal; statistically nonsignificant).
The lower disease penetrance estimates and sluggish decline of adrenal tumor diameters call for more widespread adoption of adrenal-sparing and parathyroid preservation surgery based on early and regular biochemical screening.
确定多发性内分泌腺瘤病2A型（MEN 2A）中嗜铬细胞瘤50%以及原发性甲状旁腺功能亢进症20 - 30%的已发表疾病外显率估计值是否可能过高，这一估计值可能反映了完全发展为MEN 2A的索引患者的过度代表性。
对来自三级转诊中心的MEN 2A高风险携带者进行横断面研究。
共有213名密码子634处RET突变的携带者，出生于1922年至2014年之间。甲状腺切除术的中位年龄为17岁，髓样甲状腺癌（MTC）的发生率为76.5%；嗜铬细胞瘤的发生率在第一个肾上腺为31.0%，中位年龄为34岁，在第二个肾上腺为18.8%，中位年龄为35岁；原发性甲状旁腺功能亢进症的发生率为10.8%，中位年龄为39岁。按出生年份分层，MTC、嗜铬细胞瘤和原发性甲状旁腺功能亢进症随着时间推移诊断时间提前：MTC从51岁提前到4岁；嗜铬细胞瘤在第一个肾上腺从51岁提前到22.5岁，在第二个肾上腺从51岁提前到29.5岁，原发性甲状旁腺功能亢进症从46岁提前到12岁（P≤0.008）。年龄的这种下降与肿瘤直径减小同时出现，甲状腺肿瘤直径减小更为明显（从20毫米减小到1.8毫米；P<0.001），肾上腺肿瘤直径减小相对不明显（第一个肾上腺从43毫米减小到30毫米，第二个肾上腺从20 - 57.5毫米减小到30.5毫米；无统计学意义）。
较低的疾病外显率估计值以及肾上腺肿瘤直径下降缓慢，这就要求基于早期定期生化筛查更广泛地采用保留肾上腺和甲状旁腺的手术。
