Marsh D J, McDowall D, Hyland V J, Andrew S D, Schnitzler M, Gaskin E L, Nevell D F, Diamond T, Delbridge L, Clifton-Bligh P, Robinson B G
Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, Australia.
Clin Endocrinol (Oxf). 1996 Feb;44(2):213-20. doi: 10.1046/j.1365-2265.1996.505292.x.
The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members.
Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC.
RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results.
Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia.
There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other.
There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.
五肽胃泌素刺激试验是用于识别2A型多发性内分泌腺瘤病（MEN 2A）和家族性甲状腺髓样癌（FMTC）中无症状个体的传统检测方法。在MEN 2A和FMTC家族中，RET原癌基因突变与疾病表型的分离鉴定使得重新审视该检测用于识别受影响家族成员的有效性成为可能。
在确定MEN 2A或FMTC家族中RET突变阳性和RET突变阴性成员后，收集连续和单次五肽胃泌素刺激试验数据。
在16个澳大利亚和新西兰的MEN 2A或FMTC家族中鉴定出RET突变。本研究纳入了对这些家族中39名个体的分析。32名个体（14名男性，18名女性）先前被确定为RET突变阴性。7名个体（6名男性，1名女性）先前被确定为RET突变阳性。两名RET突变阴性男性基于先前的五肽胃泌素试验结果接受了甲状腺切除术。
在注射后0、1、2、5和10分钟测量五肽胃泌素刺激后血清降钙素水平。对所有个体进行RET原癌基因的突变分析。在两个MEN 2A家族的两名RET突变阴性个体中，进行了甲状腺切除术并对C细胞进行定量，以确定C细胞增生的诊断。
RET突变阴性男性和女性的平均降钙素峰值反应分别为282±236和96±62（平均值±标准差）ng/l，差异有统计学意义（P < 0.013）。在16个家族中的两个家族中，7名RET突变阴性个体出现了对五肽胃泌素刺激的假阳性反应。接受甲状腺切除术的两名RET突变阴性个体的甲状腺组织学检查显示，其中一名有C细胞增生，另一名没有。
RET突变阳性个体和RET突变阴性个体的五肽胃泌素试验结果有相当大的重叠。这些结果表明，有必要对所有有患MEN 2A或FMTC风险的个体进行RET原癌基因分析，并在决定是否进行甲状腺切除术时将五肽胃泌素试验结果与RET原癌基因分析相结合。
