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Addison Disease Treatment & Management

  • Author: George T Griffing, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Jul 20, 2016
 

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.[44]
    • 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. Some hospitals mix 300-400 mg in 1 liter saline and infuse over 24 h to avoid needing to renew the infusion every 8-10 hours.
    • 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.
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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.
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Consultations

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

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Contributor Information and Disclosures
Author

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sylvester Odeke, MD, FACE Vidant Medical Group Endocrinology, Diabetes & Metabolism, Greenville, NC

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

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, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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 Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

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. Olafsson AS, Sigurjonsdottir HA. INCREASING PREVALENCE OF ADDISON DISEASE: RESULTS FROM A NATIONWIDE STUDY. Endocr Pract. 2016 Jan. 22 (1):30-5. [Medline].

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

  4. 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. 2006 Dec. 91(12):4849-53. [Medline]. [Full Text].

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

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

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

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

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

  10. 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. 2007 Jun. 83(980):420-1. [Medline].

  11. 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. 2007 Apr. 62(1):126-31. [Medline].

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

  13. 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. 2006 May. 147(5):2411-6. [Medline]. [Full Text].

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

  15. 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). 2008 Aug 15. [Medline].

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

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

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

  19. 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. 2007 Feb. 92(2):595-603. [Medline].

  20. 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. 2008 Oct 23. [Medline].

  21. 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. 2007 Dec. 157(6):757-61. [Medline].

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

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

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

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

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

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

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

  29. 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. 2010 Feb. 162(2):357-9. [Medline]. [Full Text].

  30. 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. 2006 Dec. 91(12):4781-5. [Medline]. [Full Text].

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

  32. 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].

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

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

  35. 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. 1992 Jul. 75(1):259-64. [Medline]. [Full Text].

  36. 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. 3rd ed. Philadelphia, Pa: WB Saunders; 1999. Vol 43: 1530-60.

  37. 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. 1991 Apr. 72(4):773-8. [Medline].

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

  39. 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). 1987 Jan. 26(1):53-9. [Medline].

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

  41. 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). 1982 Jul 17. 285(6336):172-3. [Medline].

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

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

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

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

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

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

  48. Chandy DD, Bhatia E. BONE MINERAL DENSITY IN PATIENTS WITH ADDISON DISEASE ON REPLACEMENT THERAPY WITH PREDNISOLONE. Endocr Pract. 2016 Apr. 22 (4):434-9. [Medline].

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

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

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

  52. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014 Jun 21. 383(9935):2152-67. [Medline].

  53. 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. 2007 Sep. 92(9):3553-9. [Medline]. [Full Text].

  54. 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. 2006 May. 91(5):1637-45. [Medline]. [Full Text].

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

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

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

  58. 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. 14th ed. New York, NY: McGraw-Hill; 1998. Vol 332: 2035-54.

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

  60. 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.

  61. 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. 1991 Nov. 67(793):984-7. [Medline]. [Full Text].

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

  63. 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. 2006 Sep. 29(8):727-31. [Medline].

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

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

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

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

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

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

  70. 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. 1955 Aug. 48(8):625-8.

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

  72. 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. 2007 Feb. 24(2):161-5. [Medline].

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

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

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