Aimaretti G, Corneli G, Baldelli R, Di Somma C, Gasco V, Durante C, Ausiello L, Rovere S, Grottoli S, Tamburrano G, Ghigo E
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy.
Clin Endocrinol (Oxf). 2003 Jul;59(1):56-61. doi: 10.1046/j.1365-2265.2003.01794.x.
Within an appropriate clinical context, GH deficiency (GHD) in adults must be demonstrated biochemically by a single provocative test. Insulin-induced hypoglycaemia (ITT) and GH-releasing hormone (GHRH) + arginine (ARG) are indicated as the tests of choice, provided that appropriate cut-off limits are defined. Although IGF-I is the best marker of GH secretory status, its measurement is not considered a reliable diagnostic tool. In fact, considerable overlap between GHD and normal subjects is present, at least when patients with suspected GHD are considered independently of the existence of other anterior pituitary defects. Considering the time and cost associated with provocative testing procedures, we aimed to re-evaluate the diagnostic power of IGF-I measurement.
To this goal, in a large population [n = 237, 139 men, 98 women, age range 20-80 years, body mass index (BMI) range 26.4 +/- 4.3 kg/m2] of well-nourished adults with total anterior pituitary deficit including severe GHD (as shown by a GH peak below the 1st centile limit of normal response to GHRH + ARG tests and/or ITT) we evaluated the diagnostic value of a single total IGF-I measurement. IGF-I levels in hypopituitary patients were evaluated based on age-related normative values in a large population of normal subjects (423 ns, 144 men and 279 women, age range 20-80 years, BMI range 18.2-24.9 kg/m2).
Mean IGF-I levels in GHD were lower than those in normal subjects in each decade, but not the oldest one (74.4 +/- 48.9 vs. 243.9 +/- 86.7 micro g/l for 20-30 years; 81.8 +/- 46.5 vs. 217.2 +/- 56.9 micro g/l for 31-40 years; 85.8 +/- 42.1 vs. 168.5 +/- 69.9 micro g/l for 41-50 years; 82.3 +/- 39.3 vs. 164.3 +/- 60.3 micro g/l for 51-60 years; 67.5 +/- 31.8 vs. 123.9 +/- 50.0 micro g/l for 61-70 years; P < 0.0001; 54.3 +/- 33.6 vs. 91.6 +/- 53.5 micro g/l for 71-80 years, P = ns). Individual IGF-I levels in GHD were below the age-related 3rd and 25th centile limits in 70.6% and 97.63% of patients below 40 years and in 34.9% and 77.8% of the remaining patients up to the 8th decade, respectively.
Total IGF-I levels are often normal even in patients with total anterior hypopituitarism but this does not rule out severe GHD that therefore ought to be verified by provocative testing of GH secretion. However, despite the low diagnostic sensitivity of this parameter, very low levels of total IGF-I can be considered definitive evidence of severe GHD in a remarkable percentage of total anterior hypopituitary patients who could therefore skip provocative testing of GH secretion.
在适当的临床背景下，成人生长激素缺乏症（GHD）必须通过单次激发试验进行生化证明。胰岛素诱导低血糖试验（ITT）和生长激素释放激素（GHRH）+精氨酸（ARG）试验被视为首选试验，前提是确定了适当的临界值。尽管胰岛素样生长因子-I（IGF-I）是生长激素分泌状态的最佳标志物，但其测量不被视为可靠的诊断工具。事实上，GHD患者与正常受试者之间存在相当大的重叠，至少在独立考虑疑似GHD患者而不考虑其他垂体前叶缺陷的存在时是这样。考虑到激发试验程序的时间和成本，我们旨在重新评估IGF-I测量的诊断价值。
为实现这一目标，在一大群营养良好的成人（n = 237，男性139名，女性98名，年龄范围20 - 80岁，体重指数（BMI）范围26.4±4.3 kg/m²）中，这些患者患有全垂体前叶功能减退症，包括严重GHD（如生长激素峰值低于GHRH + ARG试验和/或ITT正常反应的第1百分位数下限所示），我们评估了单次总IGF-I测量的诊断价值。根据一大群正常受试者（423名，男性144名，女性279名，年龄范围20 - 80岁，BMI范围18.2 - 24.9 kg/m²）中与年龄相关的正常参考值来评估垂体功能减退患者的IGF-I水平。
各年龄段GHD患者的平均IGF-I水平均低于正常受试者，但最年长的年龄段除外（20 - 30岁：74.4±48.9 vs. 243.9±86.7 μg/l；31 - 40岁：81.8±46.5 vs. 217.2±56.9 μg/l；41 - 50岁：85.8±42.1 vs. 168.5±69.9 μg/l；51 - 60岁：82.3±39.3 vs. 164.3±60.3 μg/l；61 - 70岁：67.5±31.8 vs. 123.9±50.0 μg/l；P < 0.0001；71 - 80岁：54.3±33.6 vs. 91.6±53.5 μg/l，P = 无显著差异）。40岁以下患者中，70.6%和97.63%的GHD患者个体IGF-I水平低于与年龄相关的第3和第25百分位数下限，而在其余患者直至80岁时，这一比例分别为34.9%和77.8%。
即使在全垂体前叶功能减退的患者中，总IGF-I水平通常也正常，但这并不排除严重GHD，因此应通过生长激素分泌激发试验来证实。然而，尽管该参数的诊断敏感性较低，但在相当比例的全垂体前叶功能减退患者中，极低的总IGF-I水平可被视为严重GHD的确切证据，因此这些患者可以跳过生长激素分泌激发试验。
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