Abstract
Early adrenal insufficiency is associated with cardiopulmonary dysfunction in immature infants. Isolated cortisol levels and ACTH stimulation testing may not adequately show ontogeny of postnatal cortisol secretion nor identify at risk infants. Our objectives were 1) to determine postnatal urinary cortisol excretion rate (UCER) from birth to 14 d in immature baboons and 2) to evaluate the relation between UCER and cardiac performance. UCER was assessed via 6-h blocked urine collections from birth to 336 h of age in twenty-one 125-d gestation (term = 185 d) baboons. Urinary cortisol was measured by RIA. Cardiopulmonary parameters were averaged over the same time periods as urine collection. Serial two-dimensional echocardiograms were performed. After 24-h age, a subgroup (n = 8) received up to four doses (0.5–1.0 mg/kg each) of hydrocortisone for refractory hypotension. UCER significantly increased from 0 to 6 h through 66 to 72 h age for non-cortisol-treated infants. Significantly reduced UCER patterns between birth and 24 h were found for animals subsequently requiring cortisol treatment. Cortisol-treated infants had lower mean blood pressure, worse metabolic acidosis, increased fluid needs, and impaired left ventricular function between 12 and 48 h of age. No group differences were found in gas exchange or ventilator support. We conclude that adrenal cortisol secretion significantly improves over the initial 72 h of life in the 125-d immature baboon. Failure to increase UCER after 12–24 h of life correlated with poor cardiovascular function that improved with hydrocortisone therapy. Adrenal hypofunction in the immature baboon is similar to the very preterm human and could serve as a model for future postnatal investigations.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- UCER:
-
urinary cortisol excretion rate
- VCFc:
-
velocity of circumferential fiber shortening—rate corrected
- LVWS:
-
left ventricular wall stress
- HC:
-
hydrocortisone
- Fio2:
-
fraction of inspired oxygen
References
Hanna C, Keith L, Colasurdo M, Buffkin D, Laird M, Mandel S, Cook D, LaFranchi S, Reynolds J 1993 Hypothalamic pituitary adrenal function in the extremely low birth weight infant. J Clin Endocrinol Metab 76: 384–387
Scott S, Watterberg K 1995 Effect of gestational age, postnatal age, and illness on plasma cortisol concentrations in premature infants. Pediatr Res 37: 112–116
Korte C, Styne D, Merritt T, Mayes D, Wertz A, Helbock H 1996 Adrenocortical function in the very low birth weight infant: improved testing sensitivity and association with neonatal outcome. J Pediatr 128: 257–263
Ng P, Wong G, Lam C, Lee C, Wong M, Fok T, Wong W, Chan D 1997 The pituitary-adrenal response to exogenous human corticotropin-releasing hormone in preterm, very low birth weight infants. J Clin Endocrinol Metab 82: 797–799
Huysman M, Hokken-Koelega A, De Ridder M, Sauer P 2000 Adrenal function in sick very preterm infants. Pediatr Re 48: 629–633
Helbock H, Insoft R, Conte F 1993 Glucocorticoid-responsive hypotension in extremely low birth weight newborns. Pediatrics 92: 715–717
Seri I, Tan R, Evans J 2001 Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension. Pediatrics 107: 1070–1074
Watterberg K, Scott S 1995 Evidence of early adrenal insufficiency in babies who develop bronchopulmonary dysplasia. Pediatrics 95: 120–125
Banks B, Stouffer N, Cnaan A, Ning Y, Merrill J, Ballard R, Ballard P 2001 Association of plasma cortisol and chronic lung disease in preterm infants. Pediatrics 107: 494–498
Watterberg K, Gerdes J, Gifford K, Lin H 1999 Prophylaxis against early adrenal in-sufficiency to prevent chronic lung disease in preterm infants. Pediatrics 104: 1258–1263
Jaffe R, Seron-Ferre M, Parer J, Lawrence C 1978 The primate fetal pituitary-adrenal axis in the perinatal period. Am J Obstet Gynecol 131: 164–169
Pepe G, Albrecht E 1990 Regulation of the primate fetal adrenal cortex. Endocr Rev 11: 151–176
Ducsay C, Hess D, McClellan M, Novy M 1991 Endocrine and morphological maturation of the fetal and neonatal adrenal cortex in baboons. J Clin Endocrinol Metab 73: 385–395
Taylor A, Lally K, Chwals W, McCurnin D, Gerstmann D, Shade R, deLemos R 1993 Hormonal response of the premature primate to operative stress. J Pediatr Surg 28: 844–846
Coulter C, Martin M, Voytek C, Hofmann J, Jaffe R 1993 Response to hemorrhagic stress in the rhesus monkey fetus in utero: effects on the pituitary-adrenal axis. J Clin Endocrinol Metab 76: 1234–1240
Coalson J, Winter V, Siler-Khodr T, Yoder B 1999 Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 160: 1333–1346
Yoder B, Siler-Khodr T, Winter V, Coalson J 2000 High-frequency oscillatory ventilation. Effects on lung function, mechanics, and cytokines in the immature baboon model of neonatal chronic lung disease. Am J Respir Crit Care Med 162: 1867–1876
Sahn D, Deely W, Hagan A, Freidman W 1974 Echocardiographic assessment of left ventricular performance in normal newborns. Circulation 49: 232–236
Bryant R, Shirley R, Ott D, Feltes T 1998 Left ventricular performance following arterial switch operation: Use of noninvasive wall stress analysis in the postoperative period. Crit Care Med 926: 926–932
Rowland D, Gutgesell H 1994 Use of mean arterial blood pressure for noninvasive determination of left ventricule wall stress in infants and children. Am J Cardiol 74: 98–99
Gaissmaier R, Pohlandt F 1999 Single-dose dexamethasone treatment of hypotension in preterm infants. J Pediatr 134: 701–705
Fauser A, Pohlandt F, Bartmann P, Gortner L 1993 Rapid increase of blood pressure in extremely low birth weight infants after a single dose of dexamethasone. Eur J Pediatr 152: 354–356
Kopelman A, Moise A, Holbert D, Hegemier S 1999 A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants. J Pediatr 135: 345–350
Tantivit P, Subramanian N, Garg M, Ramanathan R, deLemos R 1999 Low serum cortisol in term newborns with refractory hypotension. J Perinatol 19: 352–357
Hanna C, Jett P, Laird M, Mandel S, LaFranchi S, Reynolds J 1997 Corticosteroid binding globulin, total serum cortisol, and stress in extremely low-birth-weight infants. Am J Perinatol 14: 201–204
Lee M, Rajagopalan L, Berg G, Moshang T 1989 Serum adrenal steroid concentrations in premature infants. J Clin Endocrinol Metab 69: 1133–1136
Trainer P, McHardy K, Harvey R, Reid I 1993 Urinary free cortisol in the assessment of hydrocortisone replacement therapy. Horm Metab Res 25: 117–120
Siamopoulou-Mavridou A, Mavridis A, Vizandiadis A, Harsoulis P 1986 Free urinary cortisol immunoreactive levels in premature and full term infants. Acta Paediatr Scand 75: 919–922
Shenker Y, Skatrud J 2001 Adrenal insufficiency in critically ill patients. Am J Respir Crit Care Med 163: 1520–1523
Lamberts S, Bruining H, de Jong F 1997 Corticosteroid therapy in severe illness. N Engl J Med 337: 1285–1292
Hadcock J, Malbon C 1988 Regulation of β-adrenergic receptors by “permissive” hormones: corticosteroids increase steady-state levels of receptor mRNA. Proc Natl Acad Sci U S A 85: 8415–8419
Tseng Y, Tucker M, Kashiwai K, Waschek J, Padbury J 1995 Regulation of beta 1-adrenoceptors by glucocorticoids and thyroid hormones in fetal sheep. Eur J Pharmacol 289: 353–359
Padbury J, Polk D, Ervin M, Berry L, Ikegami M, Jobe A 1995 Postnatal cardiovascular and metabolic response to a single intramuscular dose of betamethasone in fetal sheep born prematurely by cesarean section. Pediatr Res 38: 709–715
Yano K, Tsuda Y, Kaji Y, Kanaya S, Fujino T, Niho Y 1994 Effects of hydrocortisone on transmembrane currents in guinea pig ventricular myocytes—possible evidence for positive inotropism. Jpn Circ J 58: 836–843
Kunz D, Walker G, Eberhardt W, Pfeilschifter J 1996 Molecular mechanisms of dexamethasone inhibition of nitric oxide synthase expression in inter-leukin 1β-stimulated mesangial cells: evidence for the involvement of tran-scriptional and posttranscriptional regulation. Proc Natl Acad Sci U S A 93: 255–259
Mesiano S, Jaffe R 1997 Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev 18: 378–403
Okur H, Kucukaydin M, Ustdal M 1995 The endocrine and metabolic response to surgical stress in the neonate. J Pediatr Surg 30: 626–630
Levine A, Cohen D, Zadik Z 1994 Urinary free cortisol values in children under stress. J Pediatr 125: 853–857
Acknowledgements
The authors thank all the personnel that support the BPD Resource Center: the animal husbandry group led by Drs. D. Carey and M. Leland, and the NICU staff (D. Correll, W. Cox, L. Kalisky, L. Nicley, S. Salazar, S. Ali, and R. Degan) for the excellent care they provide.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by National Institutes of Health grants HL52636-02 and HL52646.
Rights and permissions
About this article
Cite this article
Yoder, B., Martin, H., McCurnin, D. et al. Impaired Urinary Cortisol Excretion and Early Cardiopulmonary Dysfunction in Immature Baboons. Pediatr Res 51, 426–432 (2002). https://doi.org/10.1203/00006450-200204000-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200204000-00006
This article is cited by
-
New insights into the roles of glucocorticoid signaling dysregulation in pathological cardiac hypertrophy
Heart Failure Reviews (2022)
-
Association between plasma cortisol and death or vasopressor refractory hypotension in preterm neonates: a prospective, cohort study
Journal of Perinatology (2018)
-
Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone
Journal of Perinatology (2012)
-
Clinical characterization and long-term prognosis of neurological development in preterm infants with late-onset circulatory collapse
Journal of Perinatology (2010)
-
Relative adrenal insufficiency in the preterm and term infant
Journal of Perinatology (2009)
