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Corticosteroid binding globulin, total serum cortisol, and stress in extremely low-birth-weight infants
C E Hanna1, P L Jett, M R Laird
1Department of Pediatrics, Doernbecher Children's Hospital, Oregon Health Sciences University, Portland, USA.
Insights
Low corticosteroid binding globulin (CBG) does not explain low total cortisol in extremely low-birth-weight (ELBW) infants. However, low cortisol levels in sick ELBW infants may indicate adrenal insufficiency, similar to adults.
Area of Science:
- Neonatalogy
- Endocrinology
- Pediatric Critical Care
Background:
- Extremely low-birth-weight (ELBW) infants often exhibit low serum total cortisol levels.
- Corticosteroid binding globulin (CBG) influences cortisol bioavailability.
- The role of CBG in the low cortisol levels observed in ELBW infants is unclear.
Purpose of the Study:
- To investigate whether low corticosteroid binding globulin (CBG) levels explain the low serum total cortisol concentrations in extremely low-birth-weight (ELBW) infants.
- To assess the relationship between CBG, total cortisol, and illness severity in ELBW neonates.
- To estimate free cortisol levels and compare them to adult diagnostic criteria for adrenal insufficiency.
Main Methods:
- Prospective study of 31 ELBW infants (gestational age < 28 weeks) within the first 8 days of life.
- Measurement of serum total cortisol and CBG levels from single blood samples.
- Assessment of illness severity using the Score for Neonatal Acute Physiology Perinatal Extension (SNAP-PE).
Main Results:
- Mean serum total cortisol was 9.2 mcg/mL and mean CBG was 1.4 mg/dL.
- No significant correlation was found between total cortisol and CBG levels (r = -0.18).
- Five infants with severe illness (mean SNAP-PE score 41) had total cortisol levels ≤ 3.0 mcg/dL, with estimated free cortisol comparable to adult adrenal insufficiency.
Conclusions:
- CBG levels are lower in ELBW infants compared to term infants.
- Low CBG levels do not account for the low total cortisol observed in some critically ill ELBW infants.
- Low cortisol levels in ELBW infants may be physiologically appropriate when well but can signify adrenal insufficiency when severely ill.
Abstract:
Our objective was to determine if low levels of corticosteroid binding globulin (CBG) might explain the low serum total cortisol levels found in some extremely low-birth-weight (ELBW) infants. In a prospective study, serum total cortisol and CBG were measured in single blood samples from 31 ELBW infants, with a gestational age less than 28 weeks, in the first 8 days of life. Severity of illness was assessed using the Score for Neonatal Acute Physiology Perinatal Extension (SNAP-PE). The mean serum total cortisol (mean +/- 1 SD) was 9.2 +/- 9.8 mcg/mL and the mean CBG level was 1.4 +/- 0.31 mg/dL. There was no significant correlation between serum total cortisol and CBG levels (r = -0.18), severity of illness as measured by the SNAP-PE (r = +0.12), or birth weight (r = -0.12). Five of 31 infants, having a mean SNAP-PE score of 41, had serum total cortisol levels < or = 3.0 mcg/dL. Estimated mean serum free cortisol concentrations in these five infants (0.76 mcg/dL) were comparable to estimated free cortisol levels diagnostic of adrenal insufficiency in sick adult patients. Our findings indicate that CBG levels are lower in ELBW infants than in term infants, but low CBG levels do not explain the low serum total cortisol levels found in some very sick infants. Low cortisol levels in small premature infants may be adequate to support growth if the infant is well, but may result in a syndrome of adrenal insufficiency in those with severe illnesses.