Circulating adrenocorticotropic hormone (ACTH) and cortisol concentrations in normal, appropriate-for-gestational-age newborns versus those with sepsis and respiratory distress: Cortisol response to low-dose and standard-dose ACTH tests.

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.