What is the equivalent hydrocortisone dosing for a patient with Congenital Adrenal Hyperplasia (CAH) on dexamethasone and how is the switch done safely?

Switching from Dexamethasone to Hydrocortisone in CAH

For a patient with CAH on dexamethasone, use a potency ratio of 1 mg dexamethasone = 50-90 mg hydrocortisone when calculating the equivalent dose, then switch directly to hydrocortisone 15-25 mg daily in divided doses (typically two-thirds in the morning upon awakening and one-third in early afternoon), while adding fludrocortisone 0.05-0.2 mg daily since dexamethasone lacks the mineralocorticoid activity required for CAH management. 1, 2

Why Hydrocortisone is Preferred Over Dexamethasone

• Hydrocortisone is the drug of choice for CAH because it provides both glucocorticoid and mineralocorticoid activity, has a short half-life that allows recreation of natural diurnal rhythm, and enables physiological replacement therapy. 1

• Dexamethasone is inadequate as sole therapy for primary adrenal insufficiency and CAH because it lacks mineralocorticoid activity, is excessively potent (50-90 times more potent than hydrocortisone), and has a prolonged duration of action that prevents physiologic dosing. 1, 2

• Severe side effects with dexamethasone include large purple striae, hypercortisolism, and excessive weight gain, particularly in adolescents, making it unsuitable for long-term maintenance therapy. 3, 2

Calculating the Equivalent Dose

• Use the potency ratio of 1 mg dexamethasone = 50-90 mg hydrocortisone when converting from dexamethasone to hydrocortisone, as documented in clinical studies of CAH patients. 2

• Target hydrocortisone dose is 15-25 mg daily (approximately 10-15 mg/m² for children), which is the standard maintenance dose for adrenal insufficiency and CAH. 1

• For example, if a patient is on dexamethasone 0.5 mg daily, this would theoretically equal 25-45 mg hydrocortisone, but you should start with the standard physiologic replacement dose of 15-25 mg daily rather than using direct mathematical conversion. 1, 2

Safe Switching Protocol

Step 1: Discontinue Dexamethasone and Start Hydrocortisone

• Stop dexamethasone and immediately begin hydrocortisone at 15-25 mg daily in divided doses—there is no need for overlap or tapering when switching between these agents. 1

• Administer hydrocortisone in a divided regimen: give two-thirds of the total daily dose upon awakening (before 9 AM) and one-third in early afternoon (not later than 4-6 hours before bedtime) to mimic physiologic cortisol rhythm. 4

Step 2: Add Mineralocorticoid Replacement

• Initiate fludrocortisone 0.05-0.2 mg daily simultaneously with hydrocortisone, as dexamethasone provided no mineralocorticoid activity and patients with CAH require this replacement. 4, 1

• Even patients with "simple virilizing" CAH demonstrate elevated plasma renin and aldosterone secretion disturbances that cannot be corrected by glucocorticoid treatment alone, necessitating mineralocorticoid therapy. 5

Step 3: Monitor and Adjust

• Use clinical assessment as the primary monitoring method rather than laboratory values—look for signs of over-replacement (weight gain, insomnia, peripheral edema, striae) or under-replacement (lethargy, nausea, poor appetite, weight loss, increased pigmentation). 4

• Adjust fludrocortisone dose based on volume status, serum sodium levels, and plasma renin activity to achieve optimal mineralocorticoid replacement. 4, 5

• Titrate hydrocortisone dose based on clinical symptoms and androgen suppression, avoiding subnormal androgen levels while maintaining adequate control of virilization. 3

Critical Pitfalls to Avoid

• Do not continue dexamethasone for routine CAH management as it leads to excessive glucocorticoid exposure, inability to create physiologic cortisol rhythm, and lack of mineralocorticoid activity that can cause life-threatening hyponatremia and hypotension. 1, 2

• Do not use direct mathematical conversion from dexamethasone to hydrocortisone dose—instead, start with standard physiologic replacement doses of hydrocortisone (15-25 mg daily) regardless of the previous dexamethasone dose. 1

• Do not forget mineralocorticoid replacement when switching from dexamethasone, as patients will have had no mineralocorticoid coverage and are at risk for salt wasting even in "simple virilizing" forms of CAH. 1, 5

Patient Education Requirements

• Educate on stress dosing: patients need to double or triple their hydrocortisone dose during illness or moderate stress, and use injectable hydrocortisone for severe illness or inability to take oral medication. 4, 1

• Provide medical alert identification: all patients should wear a medical alert bracelet indicating adrenal insufficiency to ensure proper emergency management. 4, 1

• Counsel on medication interactions: anticonvulsants, antituberculosis drugs, and rifampin increase hydrocortisone requirements, while antifungals and grapefruit juice may require dose reduction. 4