Soliman Ashraf T, Taman Khaled H, Rizk Mohamed M, Nasr Ibrahim S, Alrimawy Hala, Hamido Mohamed S M
Department of Pediatrics, University of Alexandria, Alexandria, Egypt.
Metabolism. 2004 Feb;53(2):209-14. doi: 10.1016/j.metabol.2003.09.005.
In this crossover study, we compared the peak responses of cortisol to low-dose (1 microg/1.73 m(2)) and standard-dose (250 microg/1.73 m(2)) adrenocorticotropic hormone (ACTH) stimulation tests in 90 full-term newborns (37 to 42 weeks gestational age, birthweight > 2,500 g, aged 4 to 7 days): 30 with sepsis syndrome, 30 with respiratory distress (RD) and 30 normal infants. Basal cortisol and ACTH were measured in a fasting venous sample. Serum cortisol concentrations were measured 30 minutes after low-dose ACTH and 60 minutes after standard-dose ACTH by radioimmunoassay (RIA). The mean basal circulating cortisol concentration and peak cortisol responses to low-dose and standard-dose ACTH tests were higher in stressed infants with sepsis and RD compared to normal. Basal but not ACTH-stimulated cortisol concentrations were significantly higher in newborns with sepsis versus those with RD. Circulating cortisol concentrations after the low-dose ACTH test were correlated significantly with those obtained after the standard-dose ACTH test (r = 0.814, P <.001). Clinical subgrouping of septic newborns showed that those with leukopenia (5/10 died) and with meningitis (6/12 died) had significantly lower basal and peak cortisol responses to the low-dose ACTH test (but not the standard-dose ACTH test) versus those with leukocytosis (3/20 died) and without meningitis (2/18 died), respectively. In addition, septic newborns who died had significantly lower circulating cortisol concentrations and lower cortisol responses to the low-dose ACTH test (but not the standard-dose test) versus those who survived the stress. On an individual basis, only 2 septic newborns (both died) had low basal cortisol levels (<5 microg/dL) and cortisol responses less than 15 microg/dL after the low-dose ACTH test. Four more septic newborns had basal cortisol above 5 microg/dl but cortisol responses below 20 microg/dL after the low-dose ACTH test. These 4 newborns (4/30) with inadequate adrenocortical response to low-dose ACTH during sepsis had high mortality (3/4 died) and represented a subgroup of septic newborns that should be diagnosed, using a low-dose ACTH test, and treated early. These data suggest that the low-dose ACTH test may be more disciminatory than the standard-dose test among babies under stress. Increasing the cut-point level of basal cortisol in stressed infants to the lowest level of cortisol response to low-dose ACTH in normal newborns, followed by the use of a low-dose ACTH test, appears to select some newborns who need and may improve on corticosteroid therapy. Further studies are required to investigate whether supplementation with stress doses of hydrocortisone may improve the outcome in these patients.
在这项交叉研究中，我们比较了90名足月儿（胎龄37至42周，出生体重>2500g，年龄4至7天）对低剂量（1μg/1.73m²）和标准剂量（250μg/1.73m²）促肾上腺皮质激素（ACTH）刺激试验的皮质醇峰值反应：30例患有脓毒症综合征，30例患有呼吸窘迫（RD），30例为正常婴儿。在空腹静脉样本中测量基础皮质醇和ACTH。通过放射免疫分析（RIA）在低剂量ACTH注射30分钟后和标准剂量ACTH注射60分钟后测量血清皮质醇浓度。与正常婴儿相比，患有脓毒症和RD的应激婴儿的平均基础循环皮质醇浓度以及对低剂量和标准剂量ACTH试验的皮质醇峰值反应更高。脓毒症新生儿的基础皮质醇浓度（而非ACTH刺激后的皮质醇浓度）显著高于RD新生儿。低剂量ACTH试验后的循环皮质醇浓度与标准剂量ACTH试验后的浓度显著相关（r = 0.814，P<.001）。脓毒症新生儿的临床亚组分析表明，与白细胞增多（3/20死亡）和无脑膜炎（2/18死亡）的新生儿相比，白细胞减少（5/10死亡）和患有脑膜炎（6/12死亡）的新生儿对低剂量ACTH试验（而非标准剂量ACTH试验）的基础和峰值皮质醇反应显著更低。此外，与在应激中存活的新生儿相比，死亡的脓毒症新生儿的循环皮质醇浓度显著更低，对低剂量ACTH试验（而非标准剂量试验）的皮质醇反应也更低。就个体而言，只有2例脓毒症新生儿（均死亡）基础皮质醇水平低（<5μg/dL），且在低剂量ACTH试验后皮质醇反应低于15μg/dL。另有4例脓毒症新生儿基础皮质醇高于5μg/dl，但在低剂量ACTH试验后皮质醇反应低于20μg/dL。这4例（4/30）在脓毒症期间对低剂量ACTH肾上腺皮质反应不足的新生儿死亡率高（3/4死亡），代表了一组应通过低剂量ACTH试验诊断并早期治疗的脓毒症新生儿亚组。这些数据表明，在处于应激状态的婴儿中，低剂量ACTH试验可能比标准剂量试验更具鉴别力。将应激婴儿的基础皮质醇切点水平提高到正常新生儿对低剂量ACTH皮质醇反应的最低水平，然后使用低剂量ACTH试验，似乎可以筛选出一些需要并可能从皮质类固醇治疗中获益的新生儿。需要进一步研究以调查补充应激剂量的氢化可的松是否可以改善这些患者的预后。
