Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, Tinelli C, Papalia A, Casini M R, Loche S
Department of Pediatrics, University of Pavia, Italy.
Eur J Endocrinol. 2005 May;152(5):735-41. doi: 10.1530/eje.1.01911.
Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic-pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences.
In this study we evaluated the integrity of the HPA in 24 patients (age 4.2-31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency.
At a cortisol cut-off for a normal response of 550 nmol/l (20 microg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2-135.2 nmol/l (2.4-4.9 microg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST.
We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re-assessment of adrenal function.
患有器质性生长激素缺乏症（GHD）或下丘脑 - 垂体结构异常的患者可能存在额外的垂体前叶激素缺乏，并有发生完全或部分促肾上腺皮质激素（ACTH）缺乏的风险。评估下丘脑 - 垂体 - 肾上腺轴（HPA）的完整性对这些患者至关重要，因为尽管临床上无症状，但他们的HPA无法对压力刺激做出适当反应，可能会产生危及生命的后果。
在本研究中，我们评估了24例已确诊为GHD的患者（研究时年龄4.2 - 31岁）的HPA完整性，并比较了胰岛素耐量试验（ITT）、短促肾上腺皮质激素试验（SST）、低剂量促肾上腺皮质激素试验（LDSST）和促肾上腺皮质激素释放激素（CRH）试验在诊断肾上腺功能不全方面的可靠性。
以皮质醇正常反应的临界值550 nmol/l（20 μg/dl）为标准，11例受试者对ITT的反应低于正常，其中6例为先天性GHD，5例为后天性GHD。4例患者有明显的肾上腺功能不全，晨起皮质醇浓度在66.2 - 135.2 nmol/l（2.4 - 4.9 μg/dl）之间，伴有典型的临床症状和实验室检查结果。在所有这些患者中，LDSST和CRH试验均证实对ITT的皮质醇反应低于正常。SST未能将其中1例患者识别为肾上腺功能不全。在7例对ITT的皮质醇反应低于正常但无症状的患者中，LDSST确诊1例肾上腺功能不全，SST未确诊任何病例，CRH试验确诊5例。5例对ITT的皮质醇反应正常的患者在LDSST和SST后也表现出正常反应。其中只有2例在CRH试验后反应正常。在7例无症状肾上腺功能不全的患者中，晨起皮质醇平均浓度显著高于有明显肾上腺功能不全的患者。8例患者禁忌进行ITT，且他们均无明显肾上腺功能不全的临床症状。其中1例患者对LDSST、SST和CRH的皮质醇反应低于正常，3例对CRH反应低于正常，但对LDSST和SST反应正常。
我们得出结论，这些试验中没有一项能被认为在确定或排除继发性或三发性肾上腺功能不全的存在方面完全可靠。因此，临床判断仍然是决定哪些患者需要评估或重新评估肾上腺功能的最重要问题之一。
