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Klin Padiatr 2001; 213(6): 307-313
DOI: 10.1055/s-2001-18456
ORIGINALARBEIT

Georg Thieme Verlag Stuttgart · New York

Die Nebennierenrindenfunktion sehr unreifer Frühgeborener während der frühen postnatalen Phase

Adrenal function in very preterm infants in the early postnatal periodM.  Heckmann, S.  A.  Wudy
  • Zentrum für Kinderheilkunde und Jugendmedizin, Abt. Allgemeine Pädiatrie und Neonatologie, Justus-Liebig-Universität Gießen
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Publication History

Publication Date:
15 November 2001 (online)

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Zusammenfassung.

Bei sehr unreifen Frühgeborenen mit einem Gestationsalter unter 30 Schwangerschaftswochen findet sich keine Korrelation zwischen Schwere einer Erkrankung und einem Plasmakortisolwert. Während schwerer Erkrankung mit katecholaminbedürftiger arterieller Hypotension in den ersten zwei Lebenswochen wurden auffallend niedrige Kortisolwerte gemessen. Eine relative adrenale Insuffizienz wird daher vermutet. Mittels ACTH- und CRH-Test lassen sich Hypophyse und Nebennierenrinde stimulieren, wobei unklar ist, ob dies funktionell ausreichend ist. Frühgeborene mit eingeschränkter adrenaler Funktion in den ersten Lebenswochen scheinen ein erhöhtes Risiko zu haben, im Verlauf eine bronchopulmonale Dysplasie zu entwickeln. Glukokortikoide sind wirksam in der Behandlung der arteriellen Hypotension Frühgeborener und der bronchopulmonalen Dysplasie. Aufgrund des breiten Spektrums an potenziellen, zum Teil auch langfristigen Nebenwirkungen sollte die Therapie mit Glukokortikoiden nur unter sorgfältiger Abwägung von Nutzen und Risiken mit der niedrigsten wirksamen Dosis erfolgen.

In very premature infants of less than 30 weeks gestational age there is no correlation between the severity of illness and plasma cortisol concentrations. Low plasma cortisol levels were measured during critical illness with severe arterial hypotension requiring catecholamine treatment in the first two weeks of life. Thus, a relative adrenal insufficiency is suspected. The pituitary responds to CRH and the adrenal cortex to ACTH. But it is still questionable, wether the response is sufficient. Preterm infants with an impaired adrenal function in the first weeks of life seem to be at a higher risk for developing bronchopulmonary dysplasia. Steroids are effective in the treatment of arterial hypotension and bronchopulmonary dysplasia. Because of the broad spectrum of severe and long-term adverse effects, the treatment with glucocorticoids is recommended only after carefully balancing its benefits and risks.

Schlüsselwörter

Frühgeborene - Nebennierenrindenfunktion - Glukokortikoide - Hypotension - Bronchopulmonale Dysplasie

Key words

Preterm infants - adrenal function - corticosteroids - hypotension - bronchopulmonary dysplasia

Literatur

  • 1 Alkalay  A L, u. Mitarb. Hypothalamic-pituitary-adrenal axis function in very low birth weight infants treated with dexamethasone.  Pediatrics. 1990;;  86 204-210
    PubMedGoogle Scholar
  • 2 Alkalay  A L, u. Mitarb. Evaluation of hypothalamic-pituitary-adrenal axis in premature infants treated with dexamethasone.  Am J Perinatol. 1996;;  13 473-477
    PubMedGoogle Scholar
  • 3 Antonini  S R, u. Mitarb. The emergence of salivary cortisol circadian rthythm and its relationship to sleep activity in preterm infants.  Clin Endocrinol. 2000;;  52 423-426
    CrossrefPubMedGoogle Scholar
  • 4 Arnold  J D, u. Mitarb. Antenatal glucocorticoids modulate the amplitude of pulsatile cortisol secretion in premature neonates.  Pediatr Res. 1998;;  44 876-881
    PubMedGoogle Scholar
  • 5 Ballard  P L, u. Mitarb. Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome.  Pediatr Res. 1980;;  14 122-127
    PubMedGoogle Scholar
  • 6 Baldwin  W A, Allo  M. Occult hypoadrenalism in critically ill patients.  Arch Surg. 1993;;  128 673-676
    PubMedGoogle Scholar
  • 7 Boix-Ochoa  J, u. Mitarb. Cortisol response to surgical stress in neonates.  Pediatr Surg Int. 1987;;  2 267-270
    PubMedGoogle Scholar
  • 8 Bourchier  D, Weston  P J. Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birth weight infants.  Arch Dis Child. 1997;;  76 F174-178
    PubMedGoogle Scholar
  • 9 Briegel  J. Hydrokortison im septischen Schock - Renaissance einer alten Therapieform?.  Intensivmed. 1999;;  36 675-676
    CrossrefPubMedGoogle Scholar
  • 10 Celsi  G, u. Mitarb. Prenatal dexamethasone causes oligophrenia, sodium retention, and higher blood pressure in the offspring.  Pediatr Res. 1998;;  44 317-322
    PubMedGoogle Scholar
  • 11 Cole  C H, u. Mitarb. Adrenal function in premature infants during inhaled beclomethasone therapy.  J Pediatr. 1999;;  135 65-70
    PubMedGoogle Scholar
  • 12 Crowley  P. Prophylactic corticosteroids for preterm birth (Cochrane Review). In:. The Cochrane Library 1, Oxford; 2001:
    Google Scholar
  • 13 Dörr  H G, u. Mitarb. Antenatal betamethasone therapy: Effects on maternal, fetal, and neonatal mineralocorticoids, glucocorticoids, and progestins.  J Pediatr. 1986;;  108 990-993
    PubMedGoogle Scholar
  • 14 Doyle  L, Davis  P. Postnatal corticosteroids in preterm infants: Systematic review of effects on mortality and motor function.  J Paediatr Child Health. 2000;;  36 101-107
    CrossrefPubMedGoogle Scholar
  • 15 Dumas  P, u. Mitarb. Mapping of quantitative traft loci (QTL) of differential stress gene expression in rat recombinant inbred strains.  J Hypertens. 2000;;  18 545-551
    PubMedGoogle Scholar
  • 16 Economou  G, u. Mitarb. Cortisol secretion in stressed babies during neonatal period.  Horm Res. 1993;;  40 217-221
    PubMedGoogle Scholar
  • 17 Fauser  A, u. Mitarb. Rapid increase of blood pressure in extremely low birth weight infants after a single dose of dexamethasone.  Eur J Pediatr. 1993;;  152 354-356
    PubMedGoogle Scholar
  • 18 Finer  N N, Craft  A, Vaucher  Y E, Clark  R H, Sola  A. Postnatal steroids: short-term gain, long-term pain?.  J Pediatr. 2000;;  137 9-13
    CrossrefPubMedGoogle Scholar
  • 19 Ford  L R, u. Mitarb. Suppression and recovery of the neonatal hypothalamic-pituitary-adrenal axis after prolonged dexamethasone therapy.  J Pediatr. 1997;;  131 722-726
    PubMedGoogle Scholar
  • 20 Gaissmaier  R E, Pohlandt  F. Single-dose dexamethasone in hypotension in preterm infants.  J Pediatr. 1999;;  134 701-705
    PubMedGoogle Scholar
  • 21 Gray  J E, u. Mitarb. Neonatal therapeutic intervention scoring system: a therapy-based severity-of-illness index.  Pediatrics. 1992;;  90 561-567
    PubMedGoogle Scholar
  • 22 Grinspoon  S K, Biller  B MK. Laboratory Assessment of Adrenal Insufficiency.  J Clin Endocrinol Metab. 1994;;  79 923-931
    CrossrefPubMedGoogle Scholar
  • 23 Hadcock  J R, Malbon  C C. Regulation of β-adrenergic receptors by permissive hormones: Corticosteroids increase the steady-state levels of receptor mRNA.  Proc Natl Acad Sci USA. 1988;;  85 8415-8419
    PubMedGoogle Scholar
  • 24 Hanna  C E, u. Mitarb. Hypothalamic pituitary adrenal function in the extremely low birth weight infant.  J Clin Endocrinol Metab. 1993;;  76 384-387
    CrossrefPubMedGoogle Scholar
  • 25 Hanna  C E, u. Mitarb. Corticosteroid binding globulin, total serum cortisol, and stress in extremely low-birth-weight infants.  Am J Perinatol. 1997;;  14 201-204
    PubMedGoogle Scholar
  • 26 Heckmann  M, u. Mitarb. Reference range for serum cortisol in well preterm infants.  Arch Dis Child Fetal Neonatal Ed. 1999;;  81 F171-F174
    PubMedGoogle Scholar
  • 27 Heckmann  M, u. Mitarb. Serum cortisol concentrations in ill preterm infants less than 30 weeks gestational age.  Acta Paediatr. 2000;;  89 1098-1103
    PubMedGoogle Scholar
  • 28 Helbock  H J, u. Mitarb. Glucocoticoid-responsive hypotension in extremely low birth weight newborns.  Pediatrics. 1993;;  92 715-717
    PubMedGoogle Scholar
  • 29 Hingre  R V, u. Mitarb. Adrenal steroidgenesis in very low birth weight preterm infants.  J Clin Endocrinol Metab. 1994;;  78 266-270
    CrossrefPubMedGoogle Scholar
  • 30 Homoki  J, u. Mitarb. Influence of maternal antenatal treatment with betamethasone on the postnatal adrenal status in preterm infants. In: Görög S (Hrsg). Proceedings of the 4th symposium on the analysis of steroids. Académiai Kiadó, Budapest; 1990,: 333-337
    Google Scholar
  • 31 Howard  E, u. Mitarb. DNA, ganglioside and sulfatide in brains of rats given corticosterone in infancy, with an estimate of cell loss during development.  Brain Res. 1975;;  92 73-87
    CrossrefPubMedGoogle Scholar
  • 32 Huysman  M WA, u. Mitarb. Adrenal function in sick very preterm infants.  Pediatr Res. 2000;;  48 629-633
    PubMedGoogle Scholar
  • 33 Jett  P L, u. Mitarb. Variability of plasma cortisol levels in extremely low birth weight infants.  J Clin Endocrinol Metab. 1997;;  82 2921-2925
    CrossrefPubMedGoogle Scholar
  • 34 Jurney  T H, u. Mitarb. Spectrum of serum cortisol response to ACTH in ICU patients. Correlation with degree of illness and mortality.  Chest. 1987;;  92 292-295
    PubMedGoogle Scholar
  • 35 Kari  M A, u. Mitarb. Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study.  Pediatrics. 1994;;  93 730-736
    PubMedGoogle Scholar
  • 36 Kauppila  A, u. Mitarb. Umbilical cord and neonatal cortisol levels.  Obstetrics Gynecol. 1978;;  52 666-672
    PubMedGoogle Scholar
  • 37 Knowlton  A I. Adrenal insufficiency in the intensive care setting.  J Intens Care Med. 1989;;  4 35-45
    PubMedGoogle Scholar
  • 38 Kopelman  A E, u. Mitarb. A single very early dexamethasone dose improves respiratory and cardiovascular adaptation in preterm infants.  J Pediatr. 1999;;  135 345-350
    PubMedGoogle Scholar
  • 39 Korte  C, u. Mitarb. Adrenocortical function in the very low birth weight infant: improved testing sensitivity and association with neonatal outcome.  J Pediatr. 1996;;  128 257-263
    PubMedGoogle Scholar
  • 40 Krause  M. Neue Wege im Einsatz von Kortikosteroiden bei pulmonalen Erkrankungen des Frühgeborenen.  Klin Pädiatr. 1997;;  209 308-314
    PubMedGoogle Scholar
  • 41 Lamberts  S W, u. Mitarb. Corticosteroid therapy in severe illness.  N Engl J Med. 1997;;  337 1285-1292
    CrossrefPubMedGoogle Scholar
  • 42 Ledingham  I M, Watt  I. Influence of sedation on mortality in critically ill multiple trauma patients.  Lancet. 1983;;  1 1270
    PubMedGoogle Scholar
  • 43 Lee  M M, u. Mitarb. Serum adrenal steroid concentrations in premature infants.  J Clin Endocrinol Metab. 1989;;  69 1133-1136
    PubMedGoogle Scholar
  • 44 Mantagos  S, u. Mitarb. A simple stress test for the evaluation of hypothalamic-pituitary-adrenal axis during the first six months of life.  J Clin Endocrinol Metab. 1991;;  72 214-216
    PubMedGoogle Scholar
  • 45 Matthews  S G. Antenatal glucocorticoids and programming of the developing CNS.  Pediatr Res. 2000;;  47 291-300
    Google Scholar
  • 46 Merz  U, u. Mitarb. The hypothalamic-pituitary-adrenal axis in preterm infants weighing < or =1250 g: association with perinatal data and chronic lung disease.  Acta Paediatr. 1998;;  87 313-317
    CrossrefPubMedGoogle Scholar
  • 47 Metzger  D L, u. Mitarb. Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis.  J Clin Endocrinol Metab. 1993;;  77 458-463
    CrossrefPubMedGoogle Scholar
  • 48 Midgley  P C, u. Mitarb. Adrenal function in preterm infants: ACTH may not be the sole regulator of the fetal zone.  Pediatr Res. 1998;;  44 887-893
    PubMedGoogle Scholar
  • 49 Moise  A A, u. Mitarb. Antenatal steroids are associated with less need for blood pressure support in extremely premature infants.  Pediatrics. 1995;;  95 845-850
    PubMedGoogle Scholar
  • 50 Munck  A, u. Mitarb. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions.  Endocr Rev. 1984;;  5 25-44
    PubMedGoogle Scholar
  • 51 Naito  O, u. Mitarb. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery.  J Clin Endocrinol Metab. 1991;;  73 111-117
    PubMedGoogle Scholar
  • 52 Ng  P C, u. Mitarb. Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids.  J Clin Endocrinol Metab. 1997;;  82 3548-3552
    CrossrefPubMedGoogle Scholar
  • 53 Ng  P C, u. Mitarb. The pituitary-adrenal response to exogenous human corticotropin-releasing hormone in preterm, very low birth weigt infants.  J Clin Endocrinol Metab. 1997;;  82 797-799
    CrossrefPubMedGoogle Scholar
  • 54 Ng  P C. The fetal and neonatal hypothalamic-pituitary-adrenal axis.  Arch Dis Child. 2000;;  82 F250-F254
    PubMedGoogle Scholar
  • 55 Okur  H, u. Mitarb. The endocrine and metabolic response to surgical stress in the neonate.  J Pediatr Surg. 1995;;  30 626-630
    CrossrefPubMedGoogle Scholar
  • 56 Onishi  S, u. Mitarb. Postnatal development of circadian rhythm in serum cortisol levels in children.  Pediatr. 1983;;  72 399-404
    PubMedGoogle Scholar
  • 57 Papile  L A, u. Mitarb. A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants.  N Engl J Med. 1998;;  338 1112-1118
    CrossrefPubMedGoogle Scholar
  • 58 Parker  C R, u. Mitarb. Dynamics of the fetal adrenal, cholesterol, and apolipoprotein B responses to antenatal betamethasone therapy.  Am J Obstet Gynecol. 1996;;  174 562-565
    PubMedGoogle Scholar
  • 59 Richardson  D K, u. Mitarb. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care.  Pediatrics. 1993;;  91 617-623
    PubMedGoogle Scholar
  • 60 Richardson  D K, u. Mitarb. Birth weight and illness severity: independent predictors of neonatal mortality.  Pediatrics. 1993;;  91 969-975
    PubMedGoogle Scholar
  • 61 Saedi  S A, u. Mitarb. Reference ranges for serum cortisol and 17-hydroxyprogesterone levels in preterm infants.  J Pediatr. 1995;;  126 985-987
    PubMedGoogle Scholar
  • 62 Sapolsky  R M, Meaney  M J. Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period.  Brain Res Rev. 1986;;  11 65-76
    CrossrefPubMedGoogle Scholar
  • 63 Scott  S M, Watterberg  K L. Effect of gestational age, postnatal age, and illness on plasma cortisol concentrations in premature infants.  Pediatr Res. 1995;;  37 112-116
    PubMedGoogle Scholar
  • 64 Scott  S M, Wells  L. Corticosteroid-binding globulin in preterm infants in an intensive care unit.  Horm Res. 1995;;  44 218-221
    PubMedGoogle Scholar
  • 65 Seri  I. Cardiovascular, renal, and endocrine actions of dopamine in neonates and children.  J Pediatr. 1995;;  126 333-344
    PubMedGoogle Scholar
  • 66 Slotkin  T A, u. Mitarb. Fetal dexamethasone exposure impairs cellular development in neonatal rat heart and kidney: effects on DNA and Protein in whole tissue.  Teratology. 1991;;  43 301-306
    Google Scholar
  • 67 Strauss  A, u. Mitarb. Adrenal responsiveness in very-low-birth-weight infants treated with dexamethasone.  Dev Pharmacl Ther. 1992;;  19 147-154
    PubMedGoogle Scholar
  • 68 Terrone  D A, u. Mitarb. Multiple courses of betamethasone to enhance fetal lung maturation do not suppress neonatal adrenal response.  Am J Obstet Gynecol. 1999;;  180 1349-1353
    PubMedGoogle Scholar
  • 69 Tschanz  S A, u. Mitarb. Influence of postnatally administered glucocorticoids on rat lung growth.  Biol Neonate. 1995;;  68 229-245
    PubMedGoogle Scholar
  • 70 Van den Berghe  G, de Zegher  F. Anterior pituitary function during critical illness and dopamine treatment.  Crit Care Med. 1996;;  24 1580-1590
    CrossrefPubMedGoogle Scholar
  • 71 Vermes  I, u. Mitarb. Maturation of the circadian rhythm of the adrenocortical functions in human neonates and infants.  Hormon Res. 1980;;  12 237-244
    PubMedGoogle Scholar
  • 72 Vermes  I, u. Mitarb. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natriuretic hormone.  J Clin Endocrinol Metab. 1995;;  80 1238-1242
    CrossrefPubMedGoogle Scholar
  • 73 Watterberg  K L, Scott  S M. Evidence of early adrenal insufficiency in babies who develop bronchopulmonary dysplasia.  Pediatrics. 1995;;  95 120-125
    PubMedGoogle Scholar
  • 74 Watterberg  K L, u. Mitarb. Chorioamnionitis, cortisol, and acute lung disease in very low birth weight infants.  Pediatrics. 1997;;  99 E6
    PubMedGoogle Scholar
  • 75 Watterberg  K L, u. Mitarb. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease inpremature infants.  Pediatrics. 1999;;  104 1258-1263
    CrossrefPubMedGoogle Scholar
  • 76 Watterberg  K L, u. Mitarb. Links between early adrenal function and respiratory outcome in preterm infants: airway inflammation and patent ductus arteriosus.  Pediatrics. 2000;;  105 320-324
    CrossrefPubMedGoogle Scholar
  • 77 Wehling  M. Specific, nongenomic actions of steroid hormones.  Annu Rev Physiol. 1997;;  59 365-369
    CrossrefPubMedGoogle Scholar
  • 78 Wilson  D M, u. Mitarb. A randomized, placebo-controlled trial of effects of dexamethasone on hypothalamic-pituitary-adrenal axis in preterm infants.  J Pediatr. 1988;;  113 764-768
    PubMedGoogle Scholar
  • 79 Winter  S DW. Fetal and neonatal adrenocortical physiology. In: Polin RA, Fox WW (Hrsg). Fetal and neonatal physiology, 2. Aufl., WB Saunders, Philadelphia; 1998:
    Google Scholar
  • 80 Wittekind  C A, u. Mitarb. Longitudinal study of plasma ACTH and cortisol in very low birth weight infants in the first 8 weeks of life.  Early Hum Dev. 1993;;  33 191-200
    CrossrefPubMedGoogle Scholar
  • 81 Wudy  S A, u. Mitarb. Assessment of hypothalamic-pituitary-adrenocortical axis function in dexamethasone treated very low birth weight infants by a single dose metyrapone test and gas chromatographic mass spectrometric determination of urinary steroids.  J Ped Endocrinol Metab. 1995;;  8 281-286
    PubMedGoogle Scholar
  • 82 Yeh  T F, u. Mitarb. Early dexamethasone therapy in preterm infants: A follow-up study.  Pediatr. 1998;;  101 E7
    PubMedGoogle Scholar

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