Timing of Peak Serum Cortisol Values in Preterm Infants in Low-Dose and the Standard ACTH Tests

Karlsson, Riikka; Kallio, Johanna; Toppari, Jorma; Kero, Pentti

doi:10.1203/00006450-199903000-00013

Cited by 23 publications

(9 citation statements)

References 19 publications

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“…Although lower doses of corticotropin have recently been used in infants (6,12,23), in this study we wanted to compare maximal responses between these groups. Similarly, the sampling time of 30 min after ACTH administration was chosen for consistency with previous work.…”

Section: Methodsmentioning

confidence: 99%

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Impaired Glucocorticoid Synthesis in Premature Infants Developing Chronic Lung Disease

2001

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Premature infants have higher cortisol precursor concentrations than term infants; however, many sick preterm infants have surprisingly low cortisol concentrations. Those who develop chronic lung disease (CLD) have lower cortisol values than those who recover. We hypothesized that some infants have a decreased ability to synthesize cortisol, leading to physiologic disruptions including amplified inflammatory responses, thereby resulting in CLD. We measured cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone sulfate, and ACTH in 40 extremely low birth weight infants enrolled in a study of low-dose hydrocortisone therapy to prevent CLD. Thirty-four infants survived and 15 developed CLD. Hydrocortisone therapy did not suppress ACTH or any measured steroid value. Before study (Ͻ48 h of life), 17-OH progesterone was higher in CLD infants, as was the ratio of 17-OH progesterone to 11-deoxycortisol. On d 15-19 (Ն72 h after end of therapy), basal and stimulated cortisol concentrations were lower in CLD infants. In contrast, the basal ratio of 11-deoxycortisol to cortisol was higher in CLD infants, as were stimulated values of 17-OH progesterone and stimulated ratios of 17-OH progesterone to 11-deoxycortisol and 11-deoxycortisol to cortisol. Thus, infants who developed CLD had lower basal and stimulated cortisol values, but elevated cortisol precursors and precursor to product ratios, compared with infants who recovered. These data support the hypothesis that these immature infants have a decreased capacity to synthesize cortisol, which may lead to a relative adrenal insufficiency in the face of significant illness. Premature infants have elevated concentrations of cortisol precursors compared with term infants, even to the point of requiring the development of different normal screening ranges for congenital adrenal hyperplasia (1-4). Cortisol concentrations, however, are not similarly elevated in these infants; instead, many sick premature infants have surprisingly low cortisol concentrations for their degree of illness (1, 2, 5, 6). Case reports and small studies have also reported clinical signs consistent with adrenal insufficiency in such infants, such as hypotension, which respond to hydrocortisone therapy (7-10).Premature infants who develop CLD have been shown to have lower serum cortisol concentrations and decreased response to ACTH stimulation early in life (6, 11-13), compared with similar infants who recover without CLD. Because cortisol is central to the ability of the body to control inflammation, one consequence of cortisol insufficiency can be an amplified response to inflammatory stimuli (14 -16). The earliest stages in the development of CLD are characterized by broad increases in lung inflammation (17,18). We have reported that, in the first week of life, serum cortisol concentrations correlated inversely with concentrations of several cytokines and proteins in the airways of intubated premature infants (19).From these findings, we developed the hypothesi...

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Section: Methodsmentioning

confidence: 99%

“…Similarly, the sampling time of 30 min after ACTH administration was chosen for consistency with previous work. This time point has recently been shown to be appropriate in premature infants, using a standard ACTH dose of 250 g/1.73 m 2 (23). Laboratory procedures.…”

Section: Methodsmentioning

confidence: 99%

Impaired Glucocorticoid Synthesis in Premature Infants Developing Chronic Lung Disease

2001

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“…The ACTH stimulation test of 1 g has been evaluated in healthy adult volunteers, adult and pediatric patients with suspected or verified endocrine disorders, and in adults, children, and preterm infants treated with steroids (6,22,(31)(32)(33)(34). Stimulation tests using these lower doses of ACTH have been reported to be more sensitive in detecting insufficient adrenal function in critically ill preterm infants compared with the standard test (22).…”

Section: Discussionmentioning

confidence: 99%

Maturity of the Adrenal Cortex in Very Preterm Infants Is Related to Gestational Age

Bolt

2002

Pediatric Research

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To study the maturity of the adrenal cortex in preterms born before 33 wk of gestation, basal levels of cortisol and cortisone and the cortisol and 17-hydroxyprogesterone (17-OHP) response to 1 g/kg adrenocorticotropic hormone stimulation were measured in 24 appropriate-for-gestational age preterm infants (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17-OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms born Ͻ30 wk of gestation, levels of cortisol, and the ratio between cortisol/17-OHP were lower compared with preterms born between 30 and 33 wk. Levels of cortisone were higher in preterms born Ͻ30 wk, suggesting a lower activity of 11␤-hydroxysteroid dehydrogenase that may be related to maturity as well. The adrenal gland plays an important role during gestation. Steroid hormones produced by the fetal adrenal cortex are involved in the maturation of organ systems necessary for intrauterine and extrauterine life. For example, secretion of cortisol in late gestation is essential for lung maturation in sheep, rats, monkeys, and possibly humans (1, 2). It has been suggested that the adrenal cortex function may be more closely related to gestational age rather than to birth (3, 4), which implicates that in very preterm infants the adrenal activity may still be immature. Immaturity of the hypothalamic-pituitaryadrenal (HPA)-axis in preterm infants has been suggested to be associated with the occurrence of respiratory distress syndrome, chronic lung disease of prematurity, or even cardiovascular instability (5-7). Therefore, the ability of the HPA-axis to regulate, synthesize, and secrete cortisol in response to stress may be critical for survival and pulmonary development in very preterm infants.To evaluate the adrenal function the plasma cortisol response to i.v. administered ACTH is a common screening test. In general, 250 g synthetic ACTH is given as a bolus dose to stimulate cortisol release from the adrenal cortex, in adults as well as children as described by Wood et al. in 1965 (8). This supra-physiologic dose is much higher than required to produce a maximal adrenal response and could elicit an appropriate response despite of adrenal insufficiency (9, 10). Therefore, a lower dose of ACTH has been proposed to study the adrenal function.We hypothesize that differences in the maturity of the HPAaxis related to gestational age can be observed in the levels of hormones produced by the adrenal cortex and the adrenal response to ACTH in preterm infants of different gestational ages. The objective was to study basal levels of glucocorticoids and to establish the effect of stimulation of the adrenal cortex with ACTH in very preterm infants at the end of the 1st week of life. PATIENTS AND METHODS Patients.The study group consisted of 24 preterm infants with gestational ages ranging from 26 to 33 wk and birth weights ranging from 690 to 1985 g. Patients admitted to our July 11, 2001; January 10, 2002

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“…These time points were based on a study in which cortisol concentrations in infants after ACTH stimulation were measured at 30, 40, 60 and 120 min, and the maximal level was detected most often after 30 min [20]. It has been reported that the response to a low-dose ACTH test begins to diminish after 30 min [20,21]. In our study, the peak cortisol level was achieved at 40 min in 93 (94.9%) and at 30 min in 4 infants (4%).…”

Section: Discussionmentioning

confidence: 99%

Baseline and Stimulated Cortisol Levels in Preterm Infants: Is There Any Clinical Relevance?

Sarı

Dizdar²,

Oğuz³

et al. 2011

Horm Res Paediatr

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Background/Aim: To evaluate the association between the cortisol levels and clinical outcomes in preterm infants. Methods: Baseline adrenocorticotropic hormone (ACTH) and cortisol levels and ACTH-stimulated cortisol concentrations after low-dose synthetic ACTH (Synacthen®, 1 µg/kg) were measured in preterm infants <37 weeks of gestational age between the 5th and 7th days of life. Associations between cortisol concentrations and clinical outcomes were examined. The prevalence and prognostic utility of relative adrenal insufficiency (AI) were assessed. Results: Ninety-eight preterm infants were enrolled. Median baseline cortisol and ACTH levels were 13.7 µg/dl (25th-75th percentile, 9.7-21.1 µg/dl) and 11.5 pg/ml (25th-75th percentile, 6.9-22.6 pg/ml), respectively. Median peak cortisol level after ACTH stimulation was 33.6 µg/dl (25th-75th percentile, 27.2-40.2 µg/dl). The prevalence of relative AI, defined as baseline cortisol <15 µg/dl or Δ-cortisol <9 µg/dl, was 65%. Cortisol levels at baseline and at all time points during the test and relative AI were not associated with mortality or any other clinical outcomes. Conclusion: Neither baseline nor ACTH-stimulated cortisol levels were associated with clinical outcomes in preterm infants. A significant proportion of preterm infants hospitalized in the neonatal unit fulfilled the criteria for relative AI; however, relative AI did not affect outcome.

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Timing of Peak Serum Cortisol Values in Preterm Infants in Low-Dose and the Standard ACTH Tests

Cited by 23 publications

References 19 publications

Impaired Glucocorticoid Synthesis in Premature Infants Developing Chronic Lung Disease

Impaired Glucocorticoid Synthesis in Premature Infants Developing Chronic Lung Disease

Maturity of the Adrenal Cortex in Very Preterm Infants Is Related to Gestational Age

Baseline and Stimulated Cortisol Levels in Preterm Infants: Is There Any Clinical Relevance?

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