Yamaguchi K, Abe K, Adachi I, Tanaka M, Ueda M, Oka Y, Miyakawa S, Kameya T, Yanaihara N
Endocrinol Jpn. 1980 Dec;27 Suppl 1:79-86. doi: 10.1507/endocrj1954.27.supplement_79.
Three patients with the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome were studied. All had watery diarrhea, hypokalemia and hypercalcemia. Plasma vasoactive intestinal polypeptide (VIP) levels determined by radioimmunoassay were markedly elevated in these patients, indicating that they had VIP-producing tumors. Plasma VIP levels determined serially after the operation indicate that its determination is useful in estimating the effect of a treatment. As for multiple endocrine neoplasia type 1 (MEN1), two out of the three cases belonged to this category. Patient 1 had a brother with insulinoma, and in case 2, even though there was no family history, the autopsy revealed not only multiple tumors of the pancreas but also pituitary adenomas, chief cell hyperplasia of the parathyroid glands, thyroid adenomas and adrenocortical adenomas. VIP and other hormones in the tumors as well as in the plasma were examined extensively in these cases. In case 1, VIP, gastrin and calcitonin were produced in the tumor and only plasma VIP levels were elevated. In case 2, with multiple tumors, tumor 1 produced VIP, glucagon pancreatic polypeptide, gastrin and calcitonin, and tumor 2, VIP, pancreatic polypeptide, gastrin and beta-melanocyte stimulating hormone. In this case, plasma VIP, pancreatic polypeptide and glucagon levels were elevated. In case 3, VIP and calcitonin were produced in the tumor, and plasma VIP and calcitonin levels were elevated. These results indicate that (1) VIP is a good tumor marker for the WDHA syndrome due to VIP-producing tumors; (2) patients with the WDHA syndrome are sometimes associated with MEN1; and (3) VIP-producing tumors are multiple hormone-producing tumors, and VIP predominantly elevated in the plasma results in the WDHA syndrome, although other hormones such as pancreatic polypeptide, glucagon and calcitonin are sometimes found to be elevated in plasma without contributing to the clinical features.
对三名患有水样腹泻-低钾血症-无胃酸（WDHA）综合征的患者进行了研究。所有患者均有水样腹泻、低钾血症和高钙血症。通过放射免疫测定法测定的血浆血管活性肠肽（VIP）水平在这些患者中显著升高，表明他们患有产生VIP的肿瘤。术后连续测定血浆VIP水平表明，其测定有助于评估治疗效果。至于1型多发性内分泌肿瘤（MEN1），三例中有两例属于此类。病例1有一个患胰岛素瘤的兄弟，病例2尽管没有家族史，但尸检发现不仅有胰腺多发肿瘤，还有垂体腺瘤、甲状旁腺主细胞增生、甲状腺腺瘤和肾上腺皮质腺瘤。对这些病例的肿瘤以及血浆中的VIP和其他激素进行了广泛检测。病例1中，肿瘤产生VIP、胃泌素和降钙素，仅血浆VIP水平升高。病例2有多个肿瘤，肿瘤1产生VIP、胰高血糖素、胰多肽、胃泌素和降钙素，肿瘤2产生VIP、胰多肽、胃泌素和β-促黑素细胞激素。在该病例中，血浆VIP、胰多肽和胰高血糖素水平升高。病例3中，肿瘤产生VIP和降钙素，血浆VIP和降钙素水平升高。这些结果表明：（1）VIP是由产生VIP的肿瘤引起的WDHA综合征的良好肿瘤标志物；（2）WDHA综合征患者有时与MEN1相关；（3）产生VIP的肿瘤是多激素产生肿瘤，血浆中VIP显著升高导致WDHA综合征，尽管有时发现其他激素如胰多肽、胰高血糖素和降钙素在血浆中升高但对临床特征无影响。
