Leal A, Lage M, Popovic V, Torres E, Koppeschaar H P F, Paramo C, Micic D, Garcia-Mayor R V, Dieguez C, Casanueva F F
Hospital Virgen del Rocio Sevilla, Granada, Spain.
Clin Endocrinol (Oxf). 2002 Sep;57(3):377-84. doi: 10.1046/j.1365-2265.2002.01623.x.
The diagnosis of GH deficiency in adults is based on the provocative testing of GH secretion. When testing a patient with suspected GH deficiency, clinicians assess the whole secretory curve and select the GH peak as an index of secretory capability. This procedure is time consuming and the determination of GH in several samples is necessary. The combined administration of growth hormone releasing hormone (GHRH) plus growth hormone releasing peptide-6 (GHRP-6) is an effective test of GH secretion, and it has been unambiguously demonstrated that the elicited GH peak is capable of segregating normal GH secretion subjects from GH deficient patients on an individual basis. The GHRH + GHRP-6 test biochemically classifies patients into three groups; those with a stimulated GH peak >/= 20 micro g/l are considered normal and those with peaks at </= 10 micro g/l as GH deficient. The group comprising individuals between these parameters is considered uncertain, and the results are further interpreted according to clinical information, or by other tests.
As the GHRH + GHRP-6 test induces GH peaks consistently in the first 30 minutes, the working hypothesis assessed in this study was whether a single determination of GH 30 minutes after stimulus could provide the same clinical classification as the whole secretory curve.
Three hundred and forty-nine adult subjects (146 patients with organic pituitary disease and 203 healthy subjects) were studied. All were administered GHRH 1 micro g/kg i.v. plus GHRP-6 1 micro g/kg i.v. at 0 minutes, and blood samples were obtained at regular intervals. GH was determined in all samples.
GHRH + GHRP-6-evoked GH peaks in controls and patients were not correlated with GH basal values, making this determination useless for test validation. In contrast, an excellent correlation was observed between GH values at 30 minutes and the GH peaks (r = 0.994, P < 0.0001). When comparing the 30-minute GH values against the peaks, the biochemical classification changed from normal toward uncertain in only five out of 203 control subjects, which is without clinical relevance according to Bayes theorem. Similarly, when the 30-minute value was used instead of the peak in GH deficient patients, only two out of 146 patients moved from the uncertain area toward the GH deficient one. Thus, better diagnostic classification was provided for patients.
The GHRH + GHRP-6 test is a convenient, safe and reliable, provocative test of GH reserve in adults, which can be reduced to a single fixed GH determination 30 minutes after stimulus.
成人生长激素缺乏症的诊断基于生长激素分泌的激发试验。在对疑似生长激素缺乏症的患者进行检测时,临床医生会评估整个分泌曲线,并选择生长激素峰值作为分泌能力的指标。此过程耗时且需要测定多个样本中的生长激素。生长激素释放激素(GHRH)与生长激素释放肽-6(GHRP-6)联合给药是一种有效的生长激素分泌检测方法,并且已经明确证明,激发的生长激素峰值能够在个体水平上区分正常生长激素分泌的受试者和生长激素缺乏的患者。GHRH + GHRP-6试验从生化角度将患者分为三组;刺激后生长激素峰值≥20μg/L的患者被认为是正常的,而峰值≤10μg/L的患者被认为是生长激素缺乏的。处于这两个参数之间的个体组被认为结果不确定,需要根据临床信息或其他检测进一步解读结果。
由于GHRH + GHRP-6试验在最初30分钟内可持续诱导生长激素峰值,本研究评估的工作假设是刺激后30分钟单次测定生长激素是否能提供与整个分泌曲线相同的临床分类。
研究了349名成年受试者(146例患有器质性垂体疾病的患者和203名健康受试者)。所有受试者均在0分钟时静脉注射1μg/kg GHRH加1μg/kg GHRP-6,并定期采集血样。对所有样本进行生长激素测定。
对照组和患者中GHRH + GHRP-6激发的生长激素峰值与生长激素基础值无关,因此该测定对试验验证无用。相反,观察到30分钟时的生长激素值与生长激素峰值之间存在极好的相关性(r = 0.994,P < 0.0001)。将30分钟时的生长激素值与峰值进行比较时,203名对照受试者中只有5人从正常生化分类变为不确定分类,根据贝叶斯定理,这在临床上并无相关性。同样,当在生长激素缺乏的患者中用30分钟时的值代替峰值时,146名患者中只有2人从不确定区域变为生长激素缺乏区域。因此,为患者提供了更好的诊断分类。
GHRH + GHRP-6试验是一种方便、安全且可靠的成人生长激素储备激发试验,可简化为刺激后30分钟单次固定的生长激素测定。