Addison Disease Treatment & Management

  • Author: George T Griffing, MD; Chief Editor: George T Griffing, MD   more...
 
Updated: May 11, 2012
 

Medical Care

In patients in acute adrenal crisis, IV access should be established urgently, and an infusion of isotonic sodium chloride solution should be begun to restore volume deficit and correct hypotension. Some patients may require glucose supplementation. The precipitating cause should be sought and corrected where possible.

  • In stress situations, the normal adrenal gland output of cortisol is approximately 250-300 mg in 24 hours. This amount of hydrocortisone in soluble form (hydrocortisone sodium succinate or phosphate) should be given, preferably by continuous infusion.[43]
    • Administer 100 mg of hydrocortisone in 100 cc of isotonic sodium chloride solution by continuous IV infusion at a rate of 10-12 cc/h. Infusion may be initiated with 100 mg of hydrocortisone as an IV bolus.
    • An alternative method of hydrocortisone administration is 100 mg as an IV bolus every 6-8 hours.
    • The infusion method maintains plasma cortisol levels more adequately at steady stress levels, especially in the small percentage of patients who are rapid metabolizers and who may have low plasma cortisol levels between the IV boluses.
  • Clinical improvement, especially blood pressure response, should be evident within 4-6 hours of hydrocortisone infusion. Otherwise, the diagnosis of adrenal insufficiency would be questionable.
  • After 2-3 days, the stress hydrocortisone dose should be reduced to 100-150 mg, infused over a 24-hour period, irrespective of the patient's clinical status. This is to avoid stress gastrointestinal bleeding.
  • As the patient improves and as the clinical situation allows, the hydrocortisone infusion can be gradually tapered over the next 4-5 days to daily replacement doses of approximately 3 mg/h (72-75 mg over 24 h) and eventually to daily oral replacement doses, when oral intake is possible.
  • As long as the patient is receiving 100 mg or more of hydrocortisone in 24 hours, no mineralocorticoid replacement is necessary. The mineralocorticoid activity of hydrocortisone in this dosage is sufficient.
  • Thereafter, as the hydrocortisone dose is weaned further, mineralocorticoid replacement should be instituted in doses equivalent to the daily adrenal gland aldosterone output of 0.05-0.20 mg every 24 hours. The usual mineralocorticoid used for this purpose is 9-alpha-fludrocortisone, usually in doses of 0.05-0.10 mg per day or every other day.
  • Patients may need to be advised to increase salt intake in hot weather.
Next

Surgical Care

  • Parenteral steroid coverage should be used in times of major stress, trauma, or surgery and during any major procedure.
  • During surgical procedures, 100 mg of hydrocortisone should be given, preferably by the IM route, prior to the start of a continuous IV infusion. The IM dose of hydrocortisone assures steroid coverage in case of problems with the IV access.
    • When continuous IV infusion is not practical, an intermittent IV bolus injection every 6-8 hours may be used.
    • After the procedure, the hydrocortisone may be rapidly tapered within 24-36 hours to the usual replacement doses, or as gradually as the clinical situation dictates.
    • Mineralocorticoid replacement usually can be withheld until the patient resumes daily replacement steroids.
Previous
Next

Consultations

Whenever possible, an endocrinologist should be involved in both the acute care and on-going treatment of these patients.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Coauthor(s)

Sylvester Odeke, MD, FACE  Clinical Assistant Professor of Medicine, Division of Endocrinology and Metabolism, The Brody School of Medicine at East Carolina University

Sylvester Odeke, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, and North Carolina Medical Society

Disclosure: Nothing to disclose.

Steven B Nagelberg, MD  Clinical Professor, Department of Medicine, Division of Endocrinology and Metabolism, Drexel University College of Medicine

Steven B Nagelberg, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Medical Association, Endocrine Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Daniel Einhorn, MD, FACP, FACE  Medical Director, Scripps/Whittier Diabetes Institute, Department of Medicine, Associate Clinical Professor of Medicine, University of California at San Diego School of Medicine

Daniel Einhorn, MD, FACP, FACE is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Phi Beta Kappa, and Society of Nuclear Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS  Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

This chapter is dedicated to the late Dr. James C. Melby.

References

  1. Addison T. On the Constitutional and Local Effects of Disease of the Supra-renal Capsules. London, UK: Samuel Highley; 1855.

  2. Hemminki K, Li X, Sundquist J, et al. Subsequent autoimmune or related disease in asthma patients: clustering of diseases or medical care?. Ann Epidemiol. Mar 2010;20(3):217-22. [Medline].

  3. White K, Arlt W. Adrenal crisis in treated Addison's disease: a predictable but under-managed event. Eur J Endocrinol. Jan 2010;162(1):115-20. [Medline].

  4. Kyriazopoulou V. Glucocorticoid replacement therapy in patients with Addison's disease. Expert Opin Pharmacother. Apr 2007;8(6):725-9. [Medline].

  5. Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, et al. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab. Dec 2006;91(12):4849-53. [Medline]. [Full Text].

  6. Barnett AH, Espiner EA, Donald RA. Patients presenting with Addison's disease need not be pigmented. Postgrad Med J. Nov 1982;58(685):690-2. [Medline].

  7. McBrien DJ. Steatorrhea in Addison's disease. Lancet. 1963;Vol I:25-6.

  8. Van Dellen RG, Purnell DC. Hyperkalemic paralysis in Addison's disease. Mayo Clin Proc. Dec 1969;44(12):904-14.

  9. Likhari T, Magzoub S, Griffiths MJ, et al. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia. Postgrad Med J. Jun 2007;83(980):420-1. [Medline].

  10. Guo YK, Yang ZG, Li Y, et al. Addison's disease due to adrenal tuberculosis: contrast-enhanced CT features and clinical duration correlation. Eur J Radiol. Apr 2007;62(1):126-31. [Medline].

  11. Husebye E, Lovas K. Pathogenesis of primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. Apr 2009;23(2):147-57. [Medline].

  12. Husebye ES, Bratland E, Bredholt G, et al. The substrate-binding domain of 21-hydroxylase, the main autoantigen in autoimmune Addison's disease, is an immunodominant T cell epitope. Endocrinology. May 2006;147(5):2411-6. [Medline]. [Full Text].

  13. Wolff AS, Myhr KM, Vedeler CA, et al. Fc-gamma receptor polymorphisms are not associated with autoimmune Addison's disease. Scand J Immunol. Jun 2007;65(6):555-8. [Medline].

  14. Roycroft M, Fichna M, McDonald D, et al. The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22 gene) predisposes to autoimmune Addison's disease. Clin Endocrinol (Oxf). Aug 15 2008;[Medline].

  15. Elfstrom P, Montgomery SM, Kampe O, et al. Risk of primary adrenal insufficiency in patients with celiac disease. J Clin Endocrinol Metab. Sep 2007;92(9):3595-8. [Medline]. [Full Text].

  16. Betterle C, Lazzarotto F, Spadaccino AC, et al. Celiac disease in North Italian patients with autoimmune Addison's disease. Eur J Endocrinol. Feb 2006;154(2):275-9. [Medline].

  17. Biagi F, Campanella J, Soriani A, et al. Prevalence of coeliac disease in Italian patients affected by Addison's disease. Scand J Gastroenterol. Mar 2006;41(3):302-5. [Medline].

  18. Wolff AS, Erichsen MM, Meager A, et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J Clin Endocrinol Metab. Feb 2007;92(2):595-603. [Medline].

  19. Magitta NF, Boe Wolff AS, Johansson S, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes. Genes Immun. Oct 23 2008;[Medline].

  20. Gombos Z, Hermann R, Kiviniemi M, et al. Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations. Eur J Endocrinol. Dec 2007;157(6):757-61. [Medline].

  21. Glasgow BJ, Steinsapir KD, Anders K, et al. Adrenal pathology in the acquired immune deficiency syndrome. Am J Clin Pathol. Nov 1985;84(5):594-7. [Medline].

  22. Greene LW, Cole W, Greene JB, et al. Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome. Ann Intern Med. Oct 1984;101(4):497-8. [Medline].

  23. Membreno L, Irony I, Dere W, et al. Adrenocortical function in acquired immunodeficiency syndrome. J Clin Endocrinol Metab. Sep 1987;65(3):482-7. [Medline].

  24. Mukhopadhya A, Danda S, Huebner A, et al. Mutations of the AAAS gene in an Indian family with Allgrove's syndrome. World J Gastroenterol. Aug 7 2006;12(29):4764-6. [Medline].

  25. Migeon CJ, Kenny EM, Kowarski A, et al. The syndrome of congenital adrenocortical unresponsiveness to ACTH. Report of six cases. Pediatr Res. Nov 1968;2(6):501-13. [Medline].

  26. Babu K, Murthy KR, Babu N, et al. Triple A syndrome with ophthalmic manifestations in two siblings. Indian J Ophthalmol. Jul-Aug 2007;55(4):304-6. [Medline]. [Full Text].

  27. Mukherjee S, Newby E, Harvey JN. Adrenomyeloneuropathy in patients with 'Addison's disease': genetic case analysis. J R Soc Med. May 2006;99(5):245-9. [Medline].

  28. Dias RP, Chan LF, Metherell LA, et al. Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency. Eur J Endocrinol. Feb 2010;162(2):357-9. [Medline]. [Full Text].

  29. Baker BY, Lin L, Kim CJ, et al. Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia. J Clin Endocrinol Metab. Dec 2006;91(12):4781-5. [Medline]. [Full Text].

  30. Dackis CA, Gurpegui M, Pottash AL, et al. Methadone induced hypoadrenalism. Lancet. Nov 20 1982;2(8308):1167.

  31. Sekiguchi Y, Hara Y, Matsuoka H, et al. Sibling cases of Addison's disease caused by DAX-1 gene mutations. Intern Med. 2007;46(1):35-9. [Medline]. [Full Text].

  32. Elansary EH, Earis JE. Rifampicin and adrenal crisis. Br Med J (Clin Res Ed). Jun 11 1983;286(6381):1861-2.

  33. Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab. Dec 1984;59(6):1204-6.

  34. Oelkers W, Diederich S, Bahr V. 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. Jul 1992;75(1):259-64. [Medline]. [Full Text].

  35. Demers LM, Whitley RJ. Function of the adrenal cortex: protocol for the rapid ACTH test. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry. Vol 43. 3rd ed. Philadelphia, Pa: WB Saunders; 1999:1530-60.

  36. Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab. Apr 1991;72(4):773-8. [Medline].

  37. Dluhy RG, Himathongkam T, Greenfield M. Rapid ACTH test with plasma aldosterone levels. Improved diagnostic discrimination. Ann Intern Med. Jun 1974;80(6):693-6.

  38. Lindholm J, Kehlet H. Re-evaluation of the clinical value of the 30 min ACTH test in assessing the hypothalamic-pituitary-adrenocortical function. Clin Endocrinol (Oxf). Jan 1987;26(1):53-9. [Medline].

  39. May ME, Carey RM. Rapid adrenocorticotropic hormone test in practice. Retrospective review. Am J Med. Dec 1985;79(6):679-84. [Medline].

  40. Barnett AH, Donald RA, Espiner EA. High concentrations of thyroid-stimulating hormone in untreated glucocorticoid deficiency: indication of primary hypothyroidism?. Br Med J (Clin Res Ed). Jul 17 1982;285(6336):172-3. [Medline].

  41. Gharib H, Hodgson SF, Gastineau CF, et al. Reversible hypothyroidism in Addison's disease. Lancet. Oct 7 1972;2(7780):734-6. [Medline].

  42. Ma ES, Yang ZG, Li Y, et al. Tuberculous Addison's disease: morphological and quantitative evaluation with multidetector-row CT. Eur J Radiol. Jun 2007;62(3):352-8. [Medline].

  43. Lovas K, Husebye ES. Continuous subcutaneous hydrocortisone infusion in Addison's disease. Eur J Endocrinol. Jul 2007;157(1):109-12. [Medline].

  44. Debono M, Ross RJ. Doses and steroids to be used in primary and central hypoadrenalism. Ann Endocrinol (Paris). Sep 2007;68(4):265-7. [Medline].

  45. Reisch N, Arlt W. Fine tuning for quality of life: 21st century approach to treatment of Addison's disease. Endocrinol Metab Clin North Am. Jun 2009;38(2):407-18, ix-x. [Medline].

  46. Lovas K, Gjesdal CG, Christensen M, et al. Glucocorticoid replacement therapy and pharmacogenetics in Addison's disease: effects on bone. Eur J Endocrinol. Jun 2009;160(6):993-1002. [Medline].

  47. Anglin RE, Rosebush PI, Mazurek MF. The neuropsychiatric profile of Addison's disease: revisiting a forgotten phenomenon. J Neuropsychiatry Clin Neurosci. 2006;18(4):450-9. [Medline]. [Full Text].

  48. Bethune JE. The diagnosis and treatment of adrenal insufficiency. In: De Groot LJ, ed. Endocrinology. Vol 2. 2nd ed. Philadelphia, Pa: WB Saunders; 1989:1647-59.

  49. Bethune JE. The Adrenal cortex: a scope monograph. Kalamazoo, Mich: Upjohn Co; 1974.

  50. Burke CW. Adrenocortical insufficiency. Clin Endocrinol Metab. Nov 1985;14(4):947-76.

  51. Christiansen JJ, Djurhuus CB, Gravholt CH, et al. Effects of cortisol on carbohydrate, lipid, and protein metabolism: studies of acute cortisol withdrawal in adrenocortical failure. J Clin Endocrinol Metab. Sep 2007;92(9):3553-9. [Medline]. [Full Text].

  52. Coco G, Dal Pra C, Presotto F, et al. Estimated risk for developing autoimmune Addison's disease in patients with adrenal cortex autoantibodies. J Clin Endocrinol Metab. May 2006;91(5):1637-45. [Medline]. [Full Text].

  53. Donckier JE, Lacrosse M, Michel L. Bilateral adrenal lymphoma with Addison's disease : a surgical pitfall. Acta Chir Belg. Mar-Apr 2007;107(2):219-21. [Medline].

  54. Eisenbarth GS, Wilson PW, Ward F, et al. The polyglandular failure syndrome: disease inheritance, HLA type, and immune function. Ann Intern Med. Oct 1979;91(4):528-33. [Medline].

  55. Symington T, ed. Functional Pathology of the Adrenal Gland. Edinburgh, Scotland: Churchill Livingstone; 1969.

  56. Gordon WH, Dluhy RG. Diseases of the adrenal cortex. In: Fauci A, Brunwald E, Martin JB, et al, eds. Harrison's Principles of Internal Medicine. Vol 332. 14th ed. New York, NY: McGraw-Hill; 1998:2035-54.

  57. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. Apr 15 2004;350(16):1629-38.

  58. Kaplan NM. The adrenal glands. In: Griffin JE, Ojeda S, eds. Textbook of Endocrine Physiology. 3rd ed. Oxford, UK: Oxford University Press; 1996:284-313.

  59. Kasperlik-Zaluska AA, Migdalska B, Czarnocka B, Drac-Kaniewska J, Niegowska E, Czech W. Association of Addison's disease with autoimmune disorders--a long-term observation of 180 patients. Postgrad Med J. Nov 1991;67(793):984-7. [Medline]. [Full Text].

  60. Lever EG, McKerron CG. Auto-immune Addison's disease associated with hyperprolactinaemia. Clin Endocrinol (Oxf). Oct 1984;21(4):451-7. [Medline].

  61. Lovas K, Thorsen TE, Husebye ES. Saliva cortisol measurement: simple and reliable assessment of the glucocorticoid replacement therapy in Addison's disease. J Endocrinol Invest. Sep 2006;29(8):727-31. [Medline].

  62. Mason AS, Meade TW, Lee JA, et al. Epidemiological and clinical picture of Addison's disease. Lancet. Oct 5 1968;2(7571):744-7. [Medline].

  63. Meakin JW, Nelson DH, Thorn GW. Addison's disease in two brothers. J Clin Endocrinol Metab. Jun 1959;19(6):726-31.

  64. Nieman LK, Chanco Turner ML. Addison's disease. Clin Dermatol. Jul-Aug 2006;24(4):276-80. [Medline].

  65. Norbiato G, Galli M, Righini V, et al. The syndrome of acquired glucocorticoid resistance in HIV infection. Baillieres Clin Endocrinol Metab. Oct 1994;8(4):777-87. [Medline].

  66. Pombo M, Devesa J, Taborda A, et al. Glucocorticoid deficiency with achalasia of the cardia and lack of lacrimation. Clin Endocrinol (Oxf). Sep 1985;23(3):237-43. [Medline].

  67. Rose LI, Williams GH, Jagger PI, et al. The 48-hour adrenocorticotrophin infusion test for adrenocortical insufficiency. Ann Intern Med. Jul 1970;73(1):49-54.

  68. Sloper JC. The pathology of the adrenals, thymus and certain other endocrine glands in Addison's disease: an analysis of 37 necropsies. Proc R Soc Med. Aug 1955;48(8):625-8.

  69. Torrejon S, Webb SM, Rodriguez-Espinosa J, et al. Long-lasting subclinical Addison's disease. Exp Clin Endocrinol Diabetes. Sep 2007;115(8):530-2. [Medline].

  70. Walter M, McDonald CG, Paty BW, et al. Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening. Diabet Med. Feb 2007;24(2):161-5. [Medline].

  71. Waterhouse R. A case of suprarenal apoplexy. Lancet. 1911;Vol 3:577-8.

  72. Wood JB, Frankland AW, James VH, et al. A rapid test of adrenocortical function. Lancet. Jan 30 1965;191:243-5.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.