What is the difference between hydrocortisone (Cortisol) and dexamethasone, two types of corticosteroids?

From the Guidelines

Hydrocortisone and dexamethasone are distinct corticosteroids with different potencies, durations of action, and clinical uses, making hydrocortisone preferable for adrenal insufficiency and dexamethasone for conditions requiring potent anti-inflammatory effects, such as cerebral edema and oncology protocols, as seen in studies 1.

Key Differences

• Hydrocortisone is a short-acting corticosteroid with both glucocorticoid and mineralocorticoid effects, useful for adrenal insufficiency and inflammatory conditions, with a potency of 1 and a duration of action of 8-12 hours, requiring multiple daily doses 1.
• Dexamethasone is a long-acting, highly potent corticosteroid with minimal mineralocorticoid activity, approximately 25-30 times more potent than hydrocortisone, with a duration of action of 36-54 hours, often used for conditions requiring potent anti-inflammatory effects, such as severe inflammation, cerebral edema, and certain oncology protocols 1.

Clinical Applications

• Hydrocortisone is typically used for adrenal insufficiency, with dosing ranging from 15-20 mg in divided doses, and can be titrated to a maximum of 30 mg daily for residual symptoms of adrenal insufficiency, as recommended in the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.
• Dexamethasone is often used for conditions requiring potent anti-inflammatory effects, with common doses ranging from 0.5-20 mg daily, and is preferred for the management of vasogenic edema in brain metastases due to its relative lack of mineralocorticoid activity, with doses in the 4-8 mg/day range for moderately symptomatic patients 1.

Considerations

• The choice between hydrocortisone and dexamethasone should be based on the specific condition being treated, desired potency, and concern for fluid retention, with hydrocortisone carrying a higher risk of fluid retention due to its mineralocorticoid effects 1.
• The long half-life of dexamethasone increases the risk of hypothalamic-pituitary-adrenal axis suppression with prolonged use, making it essential to minimize therapy duration and taper rather than abruptly discontinue treatment 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Dexamethasone sodium phosphate has a rapid onset but short duration of action when compared with less soluble preparations. Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, including dexamethasone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects In addition, they modify the body’s immune responses to diverse stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.

The main differences between hydrocortisone (Cortisol) and dexamethasone are:

• Salt-retaining properties: Hydrocortisone has salt-retaining properties, while dexamethasone almost completely lacks this property at equipotent anti-inflammatory doses.
• Usage: Hydrocortisone is used as replacement therapy in adrenocortical deficiency states, while dexamethasone is primarily used for its potent anti-inflammatory effects in disorders of many organ systems 2, 3.
• Mechanism of action: Both are glucocorticoids, but they have different effects on the body's immune responses and metabolic effects.

From the Research

Difference between Hydrocortisone and Dexamethasone

• Hydrocortisone is a short-acting corticosteroid, whereas dexamethasone is a long-acting corticosteroid 4
• The potency of dexamethasone is about 25 times greater than that of hydrocortisone 4
• Hydrocortisone has a short elimination half-life of approximately 1.5 hours, requiring multiple dose administrations per day 5
• Dexamethasone has been shown to have a better clinical status at 28-day follow-up compared to hydrocortisone in patients with COVID-19-related acute respiratory distress syndrome 6
• In sepsis patients, dexamethasone and combined hydrocortisone and fludrocortisone treatment have been shown to reduce mortality, whereas hydrocortisone alone did not reduce the mortality risk 7

Clinical Uses

• Hydrocortisone is commonly used in the treatment of adrenal insufficiency, and is the preferred corticosteroid in patients with septic shock 8
• Dexamethasone is often used in the treatment of COVID-19-related acute respiratory distress syndrome, and has been shown to have a trend toward more favorable clinical outcomes compared to hydrocortisone and methylprednisolone 6
• Both hydrocortisone and dexamethasone are used in the treatment of various medical conditions, including croup, AIDS, hyperthyroid states, and neuropathic and cancer-related pain 4

Pharmacokinetics

• The pharmaceutical and biopharmaceutical properties of the dosage form containing hydrocortisone can affect its intestinal absorption rate and plasma concentration-time profile 5
• Factors that cause pharmacokinetic variability, such as gastrointestinal factors, should be understood and avoided where possible 5