Norton Jeffrey A, Venzon David J, Berna Marc J, Alexander H R, Fraker Douglas L, Libutti Stephen K, Marx Stephen J, Gibril Fathia, Jensen Robert T
Department of Surgery, Stanford University Medical Center, Stanford, CA 94305, USA.
Ann Surg. 2008 Mar;247(3):501-10. doi: 10.1097/SLA.0b013e31815efda5.
Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) patients with Zollinger-Ellison syndrome (ZES) is caused by parathyroid hyperplasia. Surgery for parathyroid hyperplasia is tricky and difficult. Long-term outcome in ZES/MEN1/HPT is not well known.
Eighty-four consecutive patients (49 F/35 M) with ZES/MEN1/HPT underwent initial parathyroidectomy (PTX) and were followed at 1- to 3-year intervals.
Age at PTX was 36 +/- 2 years. Mean follow-up was 17 +/- 1 years. Before PTX, mean Ca = 2.8 mmol/L (normal level (nl <2.5), PTH i = 243 pg/mL (nl <65), and gastrin = 6950 pg/mL (nl < 100). Sixty-one percent had nephrolithiasis. Each patient had parathyroid hyperplasia. Fifty-eight percent of patients had 4 parathyroid glands identified. Nine of 84 (11%) had 4 glands removed with immediate autograft, 40/84 (47%) 3 to 3.5 glands, whereas 35/84 (42%) <3 glands removed. Persistent/recurrent HPT occurred in 42%/48% of patients with <3 glands, 12%/44% with 3 to 3.5 glands, and 0%/55% with 4 glands removed. Hypoparathyroidism occurred in 3%, 10%, and 22%, respectively. The disease-free interval after surgery was significantly longer if >3 glands were removed. After surgery to correct the HPT, each biochemical parameter of ZES was improved and 20% of patients no longer had laboratory evidence of ZES.
HPT/MEN1/ZES is a severe form of parathyroid hyperplasia with a high rate of nephrolithiasis, persistent and recurrent HPT. Surgery to correct the hypercalcemia significantly ameliorates the ZES. Removal of less than 3.5 glands has an unacceptably high incidence of persistent HPT (42%), whereas 4-gland resection and transplant has a high rate of permanent hypoparathyroidism (22%). More than 3-gland resection has a longer disease-free interval. The surgical procedure of choice for patients with HPT/MEN1/ZES is 3.5-gland parathyroidectomy. Careful long-term follow-up is necessary as a significant proportion will develop recurrent HPT.
1型多发性内分泌腺瘤病（MEN1）合并卓艾综合征（ZES）患者的原发性甲状旁腺功能亢进症（HPT）是由甲状旁腺增生引起的。甲状旁腺增生的手术操作棘手且困难。ZES/MEN1/HPT的长期预后尚不清楚。
84例连续性ZES/MEN1/HPT患者（49例女性/35例男性）接受了初次甲状旁腺切除术（PTX），并按1至3年的间隔进行随访。
PTX时的年龄为36±2岁。平均随访时间为17±1年。PTX前，平均血钙=2.8 mmol/L（正常水平（nl<2.5）），甲状旁腺激素i=243 pg/mL（nl<65），胃泌素=6950 pg/mL（nl<100）。61%的患者有肾结石。每位患者均有甲状旁腺增生。58%的患者发现有4个甲状旁腺。84例中有9例（11%）切除4个腺体并立即进行自体移植，40/84例（47%）切除3至3.5个腺体，而35/84例（42%）切除少于3个腺体。切除少于3个腺体的患者中持续性/复发性HPT的发生率为42%/48%，切除3至3.5个腺体的患者为12%/44%，切除4个腺体的患者为0%/55%。甲状旁腺功能减退症的发生率分别为3%、10%和22%。如果切除超过3个腺体，术后无病生存期明显延长。纠正HPT手术后，ZES的各项生化指标均得到改善，20%的患者不再有ZES的实验室证据。
HPT/MEN1/ZES是一种严重的甲状旁腺增生形式，肾结石、持续性和复发性HPT的发生率很高。纠正高钙血症的手术可显著改善ZES。切除少于3.5个腺体时，持续性HPT的发生率高得令人无法接受（42%），而切除4个腺体并进行移植时，永久性甲状旁腺功能减退症的发生率很高（22%）。切除超过3个腺体的无病生存期更长。HPT/MEN1/ZES患者的首选手术方式是切除3.5个甲状旁腺。由于很大一部分患者会发生复发性HPT，因此需要进行仔细的长期随访。
