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:

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

Acute management

The main stay of treatment includes glucocorticosteroids and supportive therapy.

Goals

• Normalization of blood pressure and volume status.
• Supplementation of adequate glucocorticoids plus mineralocorticoid.
• When arrhythmias occur, or when potassium levels exceed 6.5 mmol/l, emergency lowering of potassium levels is mandated. Several agents are used to lowering potassium levels. The choice depends on the degree and cause of the hyperkalemia and other aspects of the patient's condition.

Supportive therapy

• Maintain airway, breathing, and circulation, and refer immediately to tertiary care center for intravenous corticosteroids.
• 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.
• Normal saline 0.9% or 5% dextrose in normal saline should be administered to correct hypotension and dehydration.
• It is usually necessary to administer 1 L rapidly and a further 2 to 4 L over the first 24 hours, to correct hypotension.
• Careful monitoring of blood pressure, fluid status, and serum sodium and potassium levels should be maintained.

Pharmacotherapy

• Dexamethasone should be given to patients with suspected Addisonian crisis prior to any laboratory measurements.
• Intravenous hydrocortisone is used to treat Addisonian crisis following dexamethasone.
• In addition, fludrocortisone is needed for mineralocorticoid replacement.

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

• Calcium supplementation (calcium gluconate 10% (10ml), preferably through a central venous catheter as the calcium may cause phlebitis) does not lower potassium but decreases myocardial excitability, protecting against life threatening arrhythmias.
• Insulin (e.g. intravenous injection of 10-15u of (short acting) insulin (e.g. Actrapid) {along with 50ml of 50% dextrose to prevent hypoglycemia}) will lead to a shift of potassium ions into cells, secondary to increased activity of the sodium-potassium ATPase.
• Bicarbonate therapy (e.g. 1 ampule (45mEq) infused over 5 minutes) is effective in cases of metabolic acidosis. The bicarbonate ion will stimulate an exchange of cellular H⁺ for Na⁺, thus leading to stimulation of the sodium-potassium ATPase.
• Salbutamol (albuterol, Ventolin^®) is a β₂-selective catecholamine that is administered by nebulizer (e.g. 10-20 mg). This drug promotes movement of potassium into cells, lowering the blood levels.
• Polystyrene sulfonate (Calcium Resonium, Kayexalate) is a binding resin that binds potassium within the intestine and removes it from the body by defecation. Calcium Resonium (15g three times a day in water) can be given by mouth. Kayexalate can be given by mouth or as an enema. In both cases, the resin absorbs potassium within the intestine and carries it out of the body by defecation. This medication may cause diarrhea.
• Refractory or severe cases may need dialysis to remove the potassium from the circulation.
• Preventing recurrence of hyperkalemia typically involves reduction of dietary potassium, removal of an offending medication, and/or the addition of a diuretic (such as furosemide (Lasix^®) or hydrochlorothiazide).
• Patiromer anion is a potassium binding ion cation exchange polymer that increases the gastrointestinal excretion of potassium (it is available in 8.4, 16.8, and 25.2 grams of powder in packets to be administered once daily). Patiromer should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

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'

• Preferred regimen (1): Fludrocortisone : 0.1 to 0.2 mg orally once daily

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

• Alternative regimen (5): Hydrocortisone sodium succinate 100 mg intravenously every 6-8 hours

Women with decreased libido

Androgen replacement

• The ovaries and the adrenals are the main source of androgens in women.
• The adrenals produce dehydroepiandrosterone (DHEA) and its sulfate, which are converted peripherally to androstenedione and testosterone.
• Women with complaints of decreased libido or sexual well-being may be treated with DHEA replacement.
• DHEA should be discontinued periodically to assess these symptoms.

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