Die Nebennierenrindenfunktion sehr unreifer Frühgeborener während der frühen postnatalen Phase

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
• 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
• 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
• 4 Arnold  J D, u. Mitarb. Antenatal glucocorticoids modulate the amplitude of pulsatile cortisol secretion in premature neonates.  Pediatr Res. 1998;;  44 876-881
• 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
• 6 Baldwin  W A, Allo  M. Occult hypoadrenalism in critically ill patients.  Arch Surg. 1993;;  128 673-676
• 7 Boix-Ochoa  J, u. Mitarb. Cortisol response to surgical stress in neonates.  Pediatr Surg Int. 1987;;  2 267-270
• 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
• 9 Briegel  J. Hydrokortison im septischen Schock - Renaissance einer alten Therapieform?.  Intensivmed. 1999;;  36 675-676
• 10 Celsi  G, u. Mitarb. Prenatal dexamethasone causes oligophrenia, sodium retention, and higher blood pressure in the offspring.  Pediatr Res. 1998;;  44 317-322
• 11 Cole  C H, u. Mitarb. Adrenal function in premature infants during inhaled beclomethasone therapy.  J Pediatr. 1999;;  135 65-70
• 12 Crowley  P. Prophylactic corticosteroids for preterm birth (Cochrane Review). In:. The Cochrane Library 1, Oxford; 2001:
• 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
• 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
• 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
• 16 Economou  G, u. Mitarb. Cortisol secretion in stressed babies during neonatal period.  Horm Res. 1993;;  40 217-221
• 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
• 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
• 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
• 20 Gaissmaier  R E, Pohlandt  F. Single-dose dexamethasone in hypotension in preterm infants.  J Pediatr. 1999;;  134 701-705
• 21 Gray  J E, u. Mitarb. Neonatal therapeutic intervention scoring system: a therapy-based severity-of-illness index.  Pediatrics. 1992;;  90 561-567
• 22 Grinspoon  S K, Biller  B MK. Laboratory Assessment of Adrenal Insufficiency.  J Clin Endocrinol Metab. 1994;;  79 923-931
• 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
• 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
• 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
• 26 Heckmann  M, u. Mitarb. Reference range for serum cortisol in well preterm infants.  Arch Dis Child Fetal Neonatal Ed. 1999;;  81 F171-F174
• 27 Heckmann  M, u. Mitarb. Serum cortisol concentrations in ill preterm infants less than 30 weeks gestational age.  Acta Paediatr. 2000;;  89 1098-1103
• 28 Helbock  H J, u. Mitarb. Glucocoticoid-responsive hypotension in extremely low birth weight newborns.  Pediatrics. 1993;;  92 715-717
• 29 Hingre  R V, u. Mitarb. Adrenal steroidgenesis in very low birth weight preterm infants.  J Clin Endocrinol Metab. 1994;;  78 266-270
• 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
• 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
• 32 Huysman  M WA, u. Mitarb. Adrenal function in sick very preterm infants.  Pediatr Res. 2000;;  48 629-633
• 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
• 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
• 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
• 36 Kauppila  A, u. Mitarb. Umbilical cord and neonatal cortisol levels.  Obstetrics Gynecol. 1978;;  52 666-672
• 37 Knowlton  A I. Adrenal insufficiency in the intensive care setting.  J Intens Care Med. 1989;;  4 35-45
• 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
• 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
• 40 Krause  M. Neue Wege im Einsatz von Kortikosteroiden bei pulmonalen Erkrankungen des Frühgeborenen.  Klin Pädiatr. 1997;;  209 308-314
• 41 Lamberts  S W, u. Mitarb. Corticosteroid therapy in severe illness.  N Engl J Med. 1997;;  337 1285-1292
• 42 Ledingham  I M, Watt  I. Influence of sedation on mortality in critically ill multiple trauma patients.  Lancet. 1983;;  1 1270
• 43 Lee  M M, u. Mitarb. Serum adrenal steroid concentrations in premature infants.  J Clin Endocrinol Metab. 1989;;  69 1133-1136
• 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
• 45 Matthews  S G. Antenatal glucocorticoids and programming of the developing CNS.  Pediatr Res. 2000;;  47 291-300
• 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
• 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
• 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
• 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
• 50 Munck  A, u. Mitarb. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions.  Endocr Rev. 1984;;  5 25-44
• 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
• 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
• 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
• 54 Ng  P C. The fetal and neonatal hypothalamic-pituitary-adrenal axis.  Arch Dis Child. 2000;;  82 F250-F254
• 55 Okur  H, u. Mitarb. The endocrine and metabolic response to surgical stress in the neonate.  J Pediatr Surg. 1995;;  30 626-630
• 56 Onishi  S, u. Mitarb. Postnatal development of circadian rhythm in serum cortisol levels in children.  Pediatr. 1983;;  72 399-404
• 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
• 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
• 59 Richardson  D K, u. Mitarb. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care.  Pediatrics. 1993;;  91 617-623
• 60 Richardson  D K, u. Mitarb. Birth weight and illness severity: independent predictors of neonatal mortality.  Pediatrics. 1993;;  91 969-975
• 61 Saedi  S A, u. Mitarb. Reference ranges for serum cortisol and 17-hydroxyprogesterone levels in preterm infants.  J Pediatr. 1995;;  126 985-987
• 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
• 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
• 64 Scott  S M, Wells  L. Corticosteroid-binding globulin in preterm infants in an intensive care unit.  Horm Res. 1995;;  44 218-221
• 65 Seri  I. Cardiovascular, renal, and endocrine actions of dopamine in neonates and children.  J Pediatr. 1995;;  126 333-344
• 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
• 67 Strauss  A, u. Mitarb. Adrenal responsiveness in very-low-birth-weight infants treated with dexamethasone.  Dev Pharmacl Ther. 1992;;  19 147-154
• 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
• 69 Tschanz  S A, u. Mitarb. Influence of postnatally administered glucocorticoids on rat lung growth.  Biol Neonate. 1995;;  68 229-245
• 70 Van den Berghe  G, de Zegher  F. Anterior pituitary function during critical illness and dopamine treatment.  Crit Care Med. 1996;;  24 1580-1590
• 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
• 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
• 73 Watterberg  K L, Scott  S M. Evidence of early adrenal insufficiency in babies who develop bronchopulmonary dysplasia.  Pediatrics. 1995;;  95 120-125
• 74 Watterberg  K L, u. Mitarb. Chorioamnionitis, cortisol, and acute lung disease in very low birth weight infants.  Pediatrics. 1997;;  99 E6
• 75 Watterberg  K L, u. Mitarb. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease inpremature infants.  Pediatrics. 1999;;  104 1258-1263
• 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
• 77 Wehling  M. Specific, nongenomic actions of steroid hormones.  Annu Rev Physiol. 1997;;  59 365-369
• 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
• 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:
• 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
• 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
• 82 Yeh  T F, u. Mitarb. Early dexamethasone therapy in preterm infants: A follow-up study.  Pediatr. 1998;;  101 E7