Nye E J, Grice J E, Hockings G I, Strakosch C R, Crosbie G V, Walters M M, Torpy D J, Jackson R V
Department of Medicine, The University of Queensland, Brisbane, Australia.
Clin Endocrinol (Oxf). 2001 Nov;55(5):625-33. doi: 10.1046/j.1365-2265.2001.01389.x.
Low doses of ACTH [1-24] (0.1, 0.5 and 1.0 microg per 1.73 m2) may provide a more physiological level of adrenal stimulation than the standard 250 microg test, but not all studies have concluded that the 1.0 microg is a more sensitive screening test for central hypoadrenalism. Eight-hour infusions of high dose ACTH [1-24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8-h infusion with the standard 250 microg test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic-pituitary disease.
Three groups of subjects were studied. A healthy control group (group 1, n = 9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n = 12, underwent IHT) and group 3 (n = 21, IHT contraindicated). Six different tests were performed: a standard IHT (0.15 U/kg soluble insulin); a 60-minute 250 microg HDT; three different LDTs using 0.1 microg, 0.5 microg and 1.0 microg (all per 1.73 m2); and an 8-h infusion test (250 microg ACTH [1-24] at a constant rate over 8 h).
Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1-24] stimulation tests. Seven of the 9 patients who failed the IHT, failed by a clear margin (peak cortisol < 85% of the lowest normal). Two of the 7 also failed all the ACTH [1-24] tests. Five of the 7 patients had discordant results, four passed the 0.1 LDT, one (out of four) passed the 0.5 LDT, none (out of three) passed the 1.0 LDT, two passed the HDT and three passed the 8-h test. Two patients were regarded as borderline fails in the IHT. Both passed the ACTH [1-24] tests, although one was a borderline pass in the 8-h test. Only five out of the 21 patients in group 3 showed discordance between the HDT and the LDTs. One patient passed the HDT and failed the 0.1 LDT, four patients failed the HDT but passed some of the different LDTS.
We conclude that in the diagnosis of central hypoadrenalism, ACTH [1-24] stimulation tests may give misleading results compared to the IHT. The use of low bolus doses of ACTH [1-24] (1.0, 0.5 or 0.1 microg) or a high dose prolonged infusion does not greatly improve the sensitivity of ACTH [1-24] testing. Dynamic tests that provide a central stimulus remain preferable in the assessment of patients with suspected ACTH deficiency.
低剂量促肾上腺皮质激素[1 - 24]（每1.73平方米0.1、0.5和1.0微克）可能比标准的250微克试验提供更接近生理水平的肾上腺刺激，但并非所有研究都得出结论认为1.0微克是诊断中枢性肾上腺皮质功能减退更敏感的筛查试验。也有人建议采用高剂量促肾上腺皮质激素[1 - 24]进行8小时输注，以此评估肾上腺持续分泌皮质醇的能力。在本研究中，我们比较了三种低剂量促肾上腺皮质激素试验（LDTs）以及8小时输注试验与标准250微克试验（HDT）和胰岛素低血糖试验（IHT）对下丘脑 - 垂体疾病患者的诊断准确性。
研究对象分为三组。一组健康对照组（第1组，n = 9），以及33例已知下丘脑或垂体疾病的患者，这些患者被分为第2组（n = 12，接受IHT）和第3组（n = 21，IHT禁忌）。进行了六种不同的试验：标准IHT（0.15 U/kg可溶性胰岛素）；60分钟的250微克HDT；三种不同的LDTs，分别使用0.1微克、0.5微克和1.0微克（均为每1.73平方米）；以及一项8小时输注试验（250微克促肾上腺皮质激素[1 - 24]在8小时内以恒定速率输注）。
第2组12例患者中有9例IHT未通过。第2组中12例明确通过IHT的患者，也通过了所有促肾上腺皮质激素[1 - 24]刺激试验。9例IHT未通过的患者中有7例明显未通过（皮质醇峰值<最低正常水平的85%）。这7例中的2例也未通过所有促肾上腺皮质激素[1 - 24]试验。7例患者中有5例结果不一致，4例通过了0.1微克LDT，4例中的1例通过了0.5微克LDT，3例中无人通过1.0微克LDT，2例通过了HDT，3例通过了8小时试验。2例患者在IHT中被视为临界未通过。两人均通过了促肾上腺皮质激素[1 - 24]试验，尽管其中一人在8小时试验中为临界通过。第3组21例患者中只有5例HDT和LDTs结果不一致。1例患者通过了HDT但未通过0.1微克LDT，4例患者未通过HDT但通过了一些不同的低剂量试验。
我们得出结论，在中枢性肾上腺皮质功能减退的诊断中，与IHT相比，促肾上腺皮质激素[1 - 24]刺激试验可能会给出误导性结果。使用低推注剂量的促肾上腺皮质激素[1 - 24]（1.0、0.5或0.1微克）或高剂量延长输注并不能显著提高促肾上腺皮质激素[1 - 24]检测的敏感性。在评估疑似促肾上腺皮质激素缺乏的患者时，提供中枢刺激的动态试验仍然更可取。
