Addison's disease medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overview

The mainstay of treatment for Addison disease is corticosteroid replacement, if there is persistent mineralocorticoid deficiency, it should be combined with fludrocortisone.

Medical therapy

The mainstay of treatment for Addison's disease is pharmacotherapy which is replacement of deficient hormones. Medical management of Addison's disease can be discussed under two categories:[1][2][3][4][5][6][7]

  • Acute management ( Addison's crisis)
  • Chronic management

Acute management

The main stay of treatment includes glucocorticosteroids and supportive therapy.

Goals

Supportive therapy

Pharmacotherapy

Adult

  • Preferred regimen (1): Dexamethasone IV 2-8 mg/dose q12h followed by an oral 0.5 mg maintenance dose.
  • Preferred regimen (1): Hydrocortisone 100 mg bolus immediately; followed by either 100 mg q8h (or) 300 mg q24 by continuous infusion for 2 to 3 days; then 100 to 150 mg q24h and taper to 75 mg/d before switching to oral maintenance dose
    • Note: Maintenance dose 10 mg in the morning, 5 mg around noon, and 5 mg in the afternoon (or) 10 to 15 mg in the morning and 5 to 10 mg in the afternoon.

Pediatric

  • Preferred regimen (1): Hydrocortisone 1 to 2 mg/kg/dose bolus immediately; followed by 25 to 150 mg/d, given in divided doses every 6 to 8 hours (in infants and young children)or150 to 250 mg/d given in divided doses every 6 to 8 hours (in older children).

Management of Hyperkalemia

Chronic management

The main stay of treatment includes glucocorticosteroids and mineralocorticoids.

Goals

  • Adequate daily supplementation of glucocorticoid and mineralocorticoid to mimic normal physiology. This should aim to maintain normal blood pressure, blood glucose, and fluid volume, and instill a sense of well-being in the patient
  • Advise patients on medication for minor illness (febrile illness or emesis) to double or triple their usual dose of glucocorticoid. In case of severe illness, they should inject themselves with a large dose of glucocorticoid and seek immediate medical attention
  • If patients are monitored to normalize ACTH level, they are almost invariably overtreated with glucocorticoid resulting in iatrogenic Cushing syndrome. Treatment monitoring is primarily based on clinical features.
  • Ensure that patients are aware that they must be vigilant in maintaining their therapeutic regimen.

Precautions

  • All patients with known Addison disease should have an emergency plan in place for corticosteroid supplementation (oral or intramuscular), to be implemented if significant illness occurs.
  • Immediate action is needed for the signs of Addisonian crisis in a known Addison disease patient
  • If the patient has pre filled syringes (emergency kit) and presents with Addisonian crisis while far from a hospital, an intramuscular injection should be given and the patient transferred to the nearest emergency room for intravenous normal saline and intravenous hydrocortisone.
  • In an undiagnosed patient who requires immediate corticosteroid treatment, dexamethasone may be given as it does not interfere with ACTH stimulation testing.

Pharmacotherapy

Glucocorticosteroid

  • Preferred regimen (1): Cortisone 10 to 37.5 mg q12h orally given in 2 divided doses with two-thirds of the total dose given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.)
  • Preferred regimen (2): Hydrocortisone : 15-30 mg/day orally given in 2 divided doses with two-thirds of the total dose given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.)
  • Preferred regimen (3): Dexamethasone : 0.25 to 0.75 mg orally once daily
  • Preferred regimen (4): Prednisone : 2.5 to 5 mg orally once daily

Mineralocorticosteroid'

mild-to-moderate stress:

  • Alternative regimen (1): Cortisone 50-100 mg/day orally given in 2 divided doses with two-thirds of the total dose given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.) for 3 days
  • Alternative regimen (2): Hydrocortisone 30-90 mg/day orally given in 2 divided doses with two-thirds of the total dose given in the morning (around 8 a.m.) and one third in the afternoon (noon to 4 p.m.) for 3 days
  • Alternative regimen (3): Dexamethasone 0.50 to 2.25 mg orally once daily for 3 days
  • Alternative regimen (4): Prednisone 5-15 mg orally once daily for 3 days

Severe stress

Women with decreased libido

Androgen replacement

  • Preferred regimen (1): DHEA 50 mg orally once daily

References

  1. Gan EH, Pearce SH (2017). "MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease". Eur. J. Endocrinol. 176 (3): R123–R135. doi:10.1530/EJE-16-0581. PMID 27810905.
  2. Inder WJ, Meyer C, Hunt PJ (2015). "Management of hypertension and heart failure in patients with Addison's disease". Clin. Endocrinol. (Oxf). 82 (6): 789–92. doi:10.1111/cen.12592. PMID 25138826.
  3. Tucci V, Sokari T (2014). "The clinical manifestations, diagnosis, and treatment of adrenal emergencies". Emerg. Med. Clin. North Am. 32 (2): 465–84. doi:10.1016/j.emc.2014.01.006. PMID 24766944.
  4. Napier C, Pearce SH (2014). "Current and emerging therapies for Addison's disease". Curr Opin Endocrinol Diabetes Obes. 21 (3): 147–53. doi:10.1097/MED.0000000000000067. PMID 24755997.
  5. Grossman A, Johannsson G, Quinkler M, Zelissen P (2013). "Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe". Eur. J. Endocrinol. 169 (6): R165–75. doi:10.1530/EJE-13-0450. PMC 3805018. PMID 24031090.
  6. Napier C, Pearce SH (2012). "Autoimmune Addison's disease". Presse Med. 41 (12 P 2): e626–35. doi:10.1016/j.lpm.2012.09.010. PMID 23177474.
  7. Quinkler M (2012). "[Addison's disease]". Med Klin Intensivmed Notfmed (in German). 107 (6): 454–9. doi:10.1007/s00063-012-0112-3. PMID 22907517.

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