Cortisone and hydrocortisone are corticosteroids, synthetic versions of hormones naturally produced by the adrenal glands. These compounds are primarily used in medicine for their powerful anti-inflammatory and immunosuppressive actions. They reduce swelling, calm allergic reactions, and suppress an overactive immune system in conditions like arthritis, asthma, and various skin disorders. Although their names and functions appear similar, they differ fundamentally in their chemical structure and how the body processes them for therapeutic effect.
Understanding the Chemical Identity
Hydrocortisone is chemically identical to cortisol, the body’s main natural stress hormone produced by the adrenal glands. Hydrocortisone is the pharmaceutical name for this substance. This molecule features an 11-beta hydroxyl group, a specific chemical structure that allows it to bind directly to receptors and exert its effects. Cortisone is a slightly different compound, lacking this crucial hydroxyl group at the 11-beta position.
The absence of this chemical group means cortisone is not immediately active in the body. Both drugs are classified as glucocorticoids, essential for processes like metabolism, blood pressure regulation, and controlling the inflammatory response. This structural distinction dictates how the body must handle each drug before it can provide therapeutic relief.
The Key Difference: Active Drug vs. Prodrug
The core distinction is that hydrocortisone is the active drug, while cortisone is considered a prodrug. As an active drug, hydrocortisone is ready to work immediately upon administration. It binds directly to glucocorticoid receptors in the cells to reduce inflammation, already being in its final, potent form.
Cortisone, the prodrug, is intrinsically inert and must undergo a metabolic transformation to become biologically active. This conversion occurs primarily in the liver, where the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces inactive cortisone into the active form, hydrocortisone (cortisol). The liver acts as a necessary activation switch for cortisone. Consequently, cortisone may be ineffective in patients with severe liver impairment who cannot properly activate the drug.
Routes of Administration and Therapeutic Applications
The difference in activation determines the common applications and routes of administration for each drug. Hydrocortisone is widely used in topical forms, such as creams and ointments, and is available over-the-counter in low-potency formulations. These topical applications target localized issues like rashes, insect bites, and mild eczema, providing immediate anti-inflammatory relief directly to the skin. Hydrocortisone is also prescribed as an oral tablet for patients with adrenal insufficiency, serving as a direct hormone replacement.
Cortisone is primarily administered systemically, either as an oral tablet or a local injection (a “cortisone shot”). When injected into an inflamed joint, the surrounding tissues and the liver convert the cortisone into active hydrocortisone, providing a sustained release of the active drug. Cortisone is rarely used topically because the skin lacks the necessary concentration of the 11β-HSD1 enzyme to efficiently activate the prodrug. For systemic use, hydrocortisone is slightly more potent than cortisone; 1 milligram of hydrocortisone equals approximately 1.25 milligrams of cortisone.
Comparing Safety Profiles and Potential Risks
The safety profile of these medications is influenced by the route of administration and the drug’s potency. Topical hydrocortisone, especially in low-dose, over-the-counter creams, carries a low risk of systemic absorption. Localized side effects include minor skin irritation, thinning of the skin, or the development of stretch marks, typically only with prolonged use. Systemic side effects are rare unless a high-potency product is used extensively over a large area for an extended period.
In contrast, both injected cortisone and oral hydrocortisone are systemic treatments that carry a higher potential for serious side effects, particularly with long-term use. Prolonged use of any systemic corticosteroid can lead to decreased bone density, muscle weakness, and symptoms resembling Cushing’s syndrome, such as weight gain and a puffy face. Systemic use also suppresses the body’s natural production of cortisol, requiring the drug to be tapered off slowly to prevent withdrawal symptoms and allow the adrenal glands to resume normal function.