adrenal%20insufficiency
ADRENAL INSUFFICIENCY
Adrenal insufficiency (AI) is the insufficient secretions of corticosteroids that may cause partial or complete destruction of the adrenal glands.
Primary AI or Addison’s disease is due to the inability of the adrenal gland to produce steroid hormones even when the stimulus by the pituitary gland via corticotrophin is adequate or increased.
Secondary AI is due to disorders of the pituitary gland that causes production of low levels of adrenocorticotropic hormone that will result to reduced cortisol levels.
Tertiary AI is the inability of the hypothalamus to produce sufficient amount of corticotropin releasing hormone.
Signs and symptoms are usually nonspecific with insidious onset.
Common signs and symptoms are fatigue, weakness, salt craving, orthostatic hypotension, nausea, vomiting, abdominal pain, diarrhea, anorexia and weight loss.

Principles of Therapy

  • Replacement doses for glucocorticoids are the same for both primary and secondary adrenal insufficiency (AI)

Pharmacotherapy

Glucocorticoid Replacement Therapy

  • Cortisone
    • Effects: Potent glucocorticoid with some mineralocorticoid activity
    • Requires enzymatic activation in the liver causing the effect to have a slower and less predictable onset
    • Short-acting therefore, 2-3 doses must be given throughout the day
  • Hydrocortisone
    • Usually considered 1st-line agent as it is the true replacement of cortisol
    • Effects: Potent glucocorticoid with some mineralocorticoid activity
    • Short-acting therefore, 2-3 doses must be given throughout the day
  • Long-acting glucocorticoids
    • Prednisolone is the preferred alternative to Hydrocortisone especially in patients with primary adrenal insufficiency who are noncompliant
    • Dexamethasone is the least preferred alternative to Hydrocortisone in patients with primary adrenal insufficiency due to high risk for Cushingoid side effects because of dose titration difficulties
    • Effects: Potent glucocorticoid with less mineralocorticoid activity than short-acting glucocorticoids
    • Long-acting which may prevent excessive high peak levels and periods of inadequate replacement that may occur with Hydrocortisone and Cortisone
Monitoring
  • Clinical assessment of body weight, postural blood pressure, energy levels and signs of flank glucocorticoid excess are used to monitor glucocorticoid replacement therapy

Dosing Equivalents of Systemic Corticosteroids (IV/Oral)

Glucocorticoid Equivalent Doses (mg)
Short acting
Cortisone acetate 25
Hydrocortisone 20
Intermediate acting
Methylprednisolone 4
Prednisolone 5
Prednisone 5
Triamcinolone 4
Long acting
Betamethasone 0.6
Dexamethasone 0.75

Mineralocorticoid Replacement Therapy

  • Mineralocorticoid replacement is necessary in all primary adrenal insufficiency patients
    • Prevents sodium loss, intravascular volume depletion and hypercalcemia
  • Fludrocortisone is the preferred choice with no salt intake restriction
    • Effects: Potent mineralocorticoid with some glucocorticoid activity
    • Dose reduction is suggested if hypertension developed during Fludrocortisone therapy
Monitoring
  • Clinical assessment of salt craving, postural hypertension or edema and blood electrolyte measurements are used to monitor mineralocorticoid replacement therapy

Androgen Replacement Therapy

  • Use of Prasterone (Dehydroepiandrosterone, DHEA) may improve well-being and sexuality in women with adrenal insufficiency (AI)
  • Recommended in women who have primary adrenal insufficiency and low libido, depressive symptoms and/or low energy levels despite optimal glucocorticoid and mineralocorticoid replacement therapy
  • Initial period of 6 months, if no benefits observed discontinue use

Treatment During Medical or Surgical Stress

  • Patients with AI may require glucocorticoid per orem or intravenous (PO or IV) supplement
  • Glucocorticoid replacement needs to be individualized
    • Patient with secondary AI caused by long-term glucocorticoid therapy may not need replacement
  • Mineralocorticoid supplement is usually not needed
Treatment of Adrenal Crisis
  • Initial goals of therapy are treatment of hypotension, correction of electrolyte abnormalities and correction of cortisol deficiency
  • Immediate intravenous (IV) dose of Hydrocortisone at an appropriate stress dose should be given
    • Prednisolone is the alternative if Hydrocortisone is not available
    • Dexamethasone IV bolus, Hydrocortisone IV bolus or any IV glucocorticoid preparation may be used in patients with known diagnosis of adrenal insufficiency
  •  2-3 L of saline solution (0.9% or 5% dextrose in 0.9% saline) should be administered as quickly as possible to restore intravascular volume and replace urinary salt losses
    • Monitor for signs of fluid overload
  • Mineralocorticoid replacement is not needed acutely because its sodium-retaining abilities become apparent only after several days
    • Adequate sodium replacement is achieved by IV saline infusion
    • May be started once saline infusion is discontinued
  • Monitor blood glucose
    • If blood glucose is <4 mmol/L, give 20% dextrose over 10-15 minutes stat
  • Identify and treat underlying problem that triggered the acute crisis
  • Most patients who experience adrenal crisis have primary adrenal insufficiency and require lifetime glucocorticoid and mineralocorticoid replacement therapy
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