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Intensivmedizin + Notfallmedizin

, Volume 42, Issue 4, pp 345–354 | Cite as

Akute Nebenniereninsuffizienz („Addison-Krise“)

  • U. WoenckhausEmail author
  • A. Vasold
  • L. C. Bollheimer
ÜBERSICHT

Zusammenfassung

Die akute Nebennierenrindeninsuffizienz (NNR-Insuffizienz) oder adrenale Krise ist die Folge eines vital bedrohlichen Mangels an Glukound Mineralokortikoiden. Ursächlich liegt in der Mehrzahl der Fälle eine primär adrenale Störung zugrunde, seltener entwickelt sich die Erkrankung sekundär bei einer hypophysären oder hypothalamischen Läsion. Pathophysiologisch dominierend für die Entwicklung des Kreislaufversagens ist der Mangel an Mineralokortikoiden. Gleichzeitig ist aber auch das Fehlen der mineralokortikoiden Eigenwirkung der körpereigenen Glukokortikoide von Bedeutung. Dass Glukokortikoide unabdingbar für die Wirksamkeit von Katecholaminen sind, wurde erst in jüngerer Zeit erkannt und erklärt das schlechte Ansprechen der unbehandelten NNR-Insuffizienz auf die Gabe von Katecholaminen. Diagnostisch hinweisende Symptome wie Müdigkeit, Abdominalschmerzen, Übelkeit und Fieber sowie charakteristische Laborveränderungen wie Hyponatriämie, Hyperkaliämie und Hypoglykämie ergeben sich aus der Kombination der verschiedenen Hormonmangelsituationen. Die Diagnosesicherung mittels Cortisol-, ACTH-Bestimmung und ACTH-Kurztest kann vor Therapieeinleitung in aller Regel nicht abgewartet werden. Basis der Behandlung ist die sofortige Bolusinjektion von 100 mg Hydrocortison, gefolgt von einer hochdosierten Bolus- oder Dauerinfusion (100 mg Hydrocortison alle 8–12 h) und Volumenersatz bis zur klinischen Stabilisierung. Die an dritter Stelle stehende Substitution von Mineralokortikoiden ist nur bei primärer NNR-Insuffizienz und dabei erst nach Absenken der Hydrocortisondosis auf <50 mg/d erforderlich. Selten kann es auch unter einer supraphysiologischen Glukokortikoidtherapie zum Auftreten einer adrenalen Krise kommen, insbesondere wenn die Behandlung abrupt abgesetzt oder rasch ausgeschlichen wird. In Ermangelung klinischer Studien dienen hier empirisch gewonnene Modelle und eine engmaschige klinische Verlaufskontrolle der Prophylaxe dieser vermeidbaren Nebenwirkung.

Schlüsselwörter

Nebenniereninsuffizienz Adrenale Krise Adrenokortikotrope Achse ACTH-Kurztest Therapie 

Adrenal crisis

Summary

Acute adrenal insufficiency or adrenal crisis is the life-threatening manifestation of glucocorticoid and mineralocorticoid deficiency. Generally, there are two types of adrenal failure: the first is caused by an adrenal disease, the second is the result of an impaired hypothalamic-pituitary-adrenal axis. A blunted mineralocorticoid production is the main pathogenic factor leading to dehydration and hypotensive shock. Diminished binding of the naturally occurring glucocorticoids on the mineralocorticoid receptor further aggravates the hemodynamic instability. More recently the important permissive effects of glucocorticoids on catecholamine action have been generally acknowledged and explain the poor responsiveness to catecholamines in untreated adrenal insufficiency. Clinical features of an adrenal crisis comprise fatigue, abdominal pain, nausea and fever. The severity of characteristic biochemical findings such as hyponatremia, hyperkalemia or hypoglycemia varies and depends on the corresponding hormone deficiencies. The diagnosis is usually confirmed by determination of circulating serum cortisol and plasma ACTH in addition to a standard corticotropin stimulation test. However, in an emergency setting laboratory results must not be awaited. After drawing the appropriate blood samples, 100 mg hydrocortisone has to be administered intravenously followed by a bolus of 100 mg every 8–12 h or by continuous infusion. The treatment has to be accompanied by sufficient fluid substitution. Replacement of mineralocorticoids in primary adrenal insufficiency is not required before the daily hydrocortisone dose has been tapered below 50 mg. Special attention has to be drawn on secondary adrenal insufficiency ensuing a glucocorticoid therapy in supraphysiologic doses. In this setting adrenal crisis develops when glucocorticoid treatment is tapered or stopped abruptly. Lacking controlled clinical studies dosage reduction of glucocorticoids is generally guided by empiricism and requires careful clinical observation.

Key words

Adrenal insufficiency adrenal crisis hypothalamic-pituitary-adrenal axis corticotropin stimulation test treatment 

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References

  1. 1.
    Lovas K, Loge JH, Husebye ES (2002) Subjective health status in Norwegian patients with Addison’s disease. Clin Endocrinol 56(5):581–588CrossRefGoogle Scholar
  2. 2.
    Arlt W, Allolio B (2003) Adrenal insufficiency. Lancet 361(9372):1881–1893CrossRefPubMedGoogle Scholar
  3. 3.
    Willis AC, Vince FP (1997) The prevalence of Addison’s disease in Coventry, UK. Postgrad Med J 73(859):286–288PubMedGoogle Scholar
  4. 4.
    Lovas K, Husebye ES (2002) High prevalence and increasing incidence of Addison’s disease in western Norway. Clin Endocrinol 56(6):787–791CrossRefGoogle Scholar
  5. 5.
    Regal M, Paramo C, Sierra SM, Garcia-Mayor RV (2001) Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol 55(6):735–740CrossRefGoogle Scholar
  6. 6.
    Hahner S, Arlt W, Allolio B (2003) Die Nebennierenkrise. Diagnostisches und therapeutisches Management der akuten Nebenniereninsuffizienz. Internist 44(10):1243–1252CrossRefPubMedGoogle Scholar
  7. 7.
    Betterle C, Dal Pra C, Mantero F, Zanchetta R (2002) Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 23(3):327–364CrossRefPubMedGoogle Scholar
  8. 8.
    Alevritis EM, Sarubbi FA, Jordan RM, Peiris AN (2003) Infectious causes of adrenal insufficiency. South Med J 96(9):888–890CrossRefPubMedGoogle Scholar
  9. 9.
    Dore GJ, Marriott DJ, Duflou JA (1995) Clinico-pathological study of cytomegalovirus (CMV) in AIDS autopsies: under-recognition of CMV pneumonitis and CMV adrenalitis. Aust N Z J Med 25(5):503–506PubMedGoogle Scholar
  10. 10.
    Findling JW, Buggy BP, Gilson IH, Brummitt CF, Bernstein BM, Raff H (1994) Longitudinal evaluation of adrenocortical function in patients infected with the human immunodeficiency virus. J Clin Endocrinol Metab 79(4):1091–1096CrossRefPubMedGoogle Scholar
  11. 11.
    Aubourg P, Chaussain JL (2003) Adrenoleukodystrophy: the most frequent genetic cause of Addison’s disease. Horm Res 59(Suppl 1):104–105CrossRefPubMedGoogle Scholar
  12. 12.
    Chanson P, Lepeintre JF, Ducreux D (2004) Management of pituitary apoplexy. Expert Opin Pharmacother 5(6):1287–1298CrossRefPubMedGoogle Scholar
  13. 13.
    McKenna TJ, Fearon U, Clarke D, Cunningham SK (1997) A critical review of the origin and control of adrenal androgens. Baillieres Clin Obstet Gynaecol 11(2):229–248PubMedGoogle Scholar
  14. 14.
    Allolio B, Ehses W, Steffen HM, Muller R (1994) Reduced lymphocyte beta 2-adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency. Clin Endocrinol 40(6):769–775Google Scholar
  15. 15.
    Zuckerman-Levin N, Tiosano D, Eisenhofer G, Bornstein S, Hochberg Z (2001) The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: a study in isolated glucocorticoid deficiency. J Clin Endocrinol Metab 86(12):5920–5924CrossRefPubMedGoogle Scholar
  16. 16.
    Bornstein SR, Breidert M, Ehrhart-Bornstein M, Kloos B, Scherbaum WA (1995) Plasma catecholamines in patients with Addison’s disease. Clin Endocrinol 42(2):215–218Google Scholar
  17. 17.
    Ishikawa S, Schrier RW (1984) Vascular effects of arginine vasopressin, angiotensin II, and norepinephrine in adrenal insufficiency. Am J Physiol 246(1 Pt 2):H104–H113PubMedGoogle Scholar
  18. 18.
    Yagil Y, Krakoff LR (1988) The differential effect of aldosterone and dexamethasone on pressor responses in adrenalectomized rats. Hypertension 11(2):174–178PubMedGoogle Scholar
  19. 19.
    Diederich S, Franzen NF, Bahr V, Oelkers W (2003) Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases. Eur J Endocrinol 148(6):609–617CrossRefPubMedGoogle Scholar
  20. 20.
    Artavia-Loria E, Chaussain JL, Bougneres PF, Job JC (1986) Frequency of hypoglycemia in children with adrenal insufficiency. Acta Endocrinol (Suppl)279:275–278Google Scholar
  21. 21.
    Tobin MV, Aldridge SA, Morris AI, Belchetz PE, Gilmore IT (1989) Gastrointestinal manifestations of Addison’s disease. Am J Gastroenterol 84(10):1302–1305PubMedGoogle Scholar
  22. 22.
    McAulay V, Frier BM (2000) Addison’s disease in type 1 diabetes presenting with recurrent hypoglycaemia. Postgrad Med J 76(894):230–232CrossRefPubMedGoogle Scholar
  23. 23.
    Dorin RI, Qualls CR, Crapo LM (2003) Diagnosis of adrenal insufficiency. Ann Intern Med 139(3):194–204PubMedGoogle Scholar
  24. 24.
    Oelkers W, Diederich S, Bahr V (1992) Diagnosis and therapy surveillance in Addison’s disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone. J Clin Endocrinol Metab 75(1):259–264CrossRefPubMedGoogle Scholar
  25. 25.
    Grinspoon SK, Biller BM (1994) Clinical review 62: laboratory assessment of adrenal insufficiency. J Clin Endocrinol Metab 79(4):923–931CrossRefPubMedGoogle Scholar
  26. 26.
    Nerup J (1974) Addison’s disease—a review of some clinical, pathological and immunological features. Dan Med Bull 21(6):201–217PubMedGoogle Scholar
  27. 27.
    Hangaard J, Andersen M, Grodum E, Koldkjaer O, Hagen C (1996) Pulsatile thyrotropin secretion in patients with Addison’s disease during variable glucocorticoid therapy. J Clin Endocrinol Metab 81(7):2502–2507CrossRefPubMedGoogle Scholar
  28. 28.
    Kraan GP, Dullaart RP, Pratt JJ, Wolthers BG, Drayer NM, De Bruin R (1998) The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different. J Clin Endocrinol Metab 83(4):1247–1252CrossRefPubMedGoogle Scholar
  29. 29.
    de Herder WW, van der Lely AJ (2003) Addisonian crisis and relative adrenal failure. Rev Endocr Metab Disord 4(2):143–147CrossRefPubMedGoogle Scholar
  30. 30.
    Quinkler M, Lepenies J, Diederich S (2003) Therapie der Nebennierenrinden-Insuffizienz Dtsch Med Wochenschr 128(12):617-618CrossRefPubMedGoogle Scholar
  31. 31.
    Groschl M, Rauh M, Dorr HG (2002) Cortisol and 17-hydroxyprogesterone kinetics in saliva after oral administration of hydrocortisone in children and young adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 87(3):1200–1204CrossRefPubMedGoogle Scholar
  32. 32.
    Brandon DD, Isabelle LM, Samuels MH, Kendall JW, Loriaux DL (1999) Cortisol production rate measurement by stable isotope dilution using gas chromatography-negative ion chemical ionization mass spectrometry. Steroids 64(6):372–378CrossRefPubMedGoogle Scholar
  33. 33.
    Smith SJ, MacGregor GA, Markandu ND et al (1984) Evidence that patients with Addison’s disease are undertreated with fludrocortisone. Lancet 1(8367):11–14CrossRefPubMedGoogle Scholar
  34. 34.
    Hunt PJ, Gurnell EM, Huppert FA et al (2000) Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial. J Clin Endocrinol Metab 85(12):4650–4656CrossRefPubMedGoogle Scholar
  35. 35.
    Arlt W, Callies F, van Vlijmen JC et al (1999) Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 341(14):1013–1020CrossRefPubMedGoogle Scholar
  36. 36.
    Arlt W, Allolio B (2003) DHEA replacement in adrenal insufficiency. J Clin Endocrinol Metab 88(8):4001; author reply-2CrossRefPubMedGoogle Scholar
  37. 37.
    Cronin CC, Callaghan N, Kearney PJ, Murnaghan DJ, Shanahan F (1997) Addison disease in patients treated with glucocorticoid therapy. Arch Intern Med 157(4):456–458CrossRefPubMedGoogle Scholar
  38. 38.
    Steward PM (2002) The Adrenal Cortex. In: Larsen PR, Melmed S, Polonsky KS (Hrsg) Williams Textbook of Endocrinology. WB Saunders Company, Philadelphia, S 491–551Google Scholar
  39. 39.
    Todd GR, Acerini CL, Ross-Russell R, Zahra S, Warner JT, McCance D (2002) Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 87(6):457–461CrossRefPubMedGoogle Scholar
  40. 40.
    Krasner AS (1999) Glucocorticoid-induced adrenal insufficiency. Jama 282(7):671–676CrossRefPubMedGoogle Scholar
  41. 41.
    Christy NP (1992) Pituitary-adrenal function during corticosteroid therapy. Learning to live with uncertainty. N Engl J Med 326(4):266–267PubMedGoogle Scholar
  42. 42.
    LaRochelle GE Jr, LaRochelle AG, Ratner RE, Borenstein DG (1993) Recovery of the hypothalamic-pituitaryadrenal (HPA) axis in patients with rheumatic diseases receiving lowdose prednisone. Am J Med 95(3):258–264CrossRefPubMedGoogle Scholar
  43. 43.
    Fauci AS (1978) Alternate-day corticosteroid therapy. Am J Med 64(5):729–731CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff Verlag 2005

Authors and Affiliations

  1. 1.Klinik und Poliklinik für Innere Medizin IUniversität RegensburgRegensburgGermany

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