Question: What are the differences between hydrocortisone, cortisone acetate, prednisone, and dexamethasone? Are there any guidelines as to when one is used versus another?

Answer: These compounds are all adrenal steroid analogs; specifically, they are called glucocorticoids. Glucocorticoids affect carbohydrate, protein, and fat metabolism, bone metabolism, and immune and inflammatory functions. In contrast, the mineralocorticoid aldosterone, also secreted by the adrenal, regulates sodium and potassium metabolism and fluid balance. The glucocorticoid that is produced by the body is cortisol, also known as hydrocortisone. Cortisone acetate is the glucocorticoid cortisone with an ester group attached that makes it soluble in water. Cortisone is biologically inactive and is rapidly converted to cortisol by the liver so that it can exert its effects. Hydrocortisone and cortisone acetate are both short-acting glucocorticoids. They are given once daily, in the early morning, to patients who are recovering from Cushing’s syndrome or are being tapered off pharmacological dosages of glucocorticoids to allow their hypothalamic -pituitary-adrenal axis to recover. These are the only circumstances in which I prescribe hydrocortisone, and I do not use cortisone acetate.

Prednisone and dexamethasone are also synthetic glucocorticoids. Prednisone is 4 to 5 times more potent than hydrocortisone and has a longer duration of action, perhaps 12 hours or more. Dexamethasone is 40 to 50 times more potent than hydrocortisone and even longer-acting, 18 to 24 hours. Both of these glucocorticoids are given when a prolonged action is desired. This includes replacing cortisol in patients with permanent adrenal insufficiency (Addison’s disease) or suppressing ACTH secretion in patients with congenital adrenal hyperplasia. In such cases, the medication is taken at bedtime, thus the patient awakens with appropriate levels of steroid. Very rarely, these medications cause insomnia if taken at night. These longer acting glucocorticoids are also used to suppress inflammation or immune rejection, and both are less expensive than hydrocortisone.

If a patient with permanent adrenal insufficiency is doing well on hydrocortisone replacement, usually split between two or three doses, the largest taken in the morning, I usually do not change the medication. However, if the patient is not doing well, I will change the medication to dexamethasone or prednisone. Some of my patients have reported remarkable improvements in their quality of life on these longer acting medications. The longer acting glucocorticoids have been reported to have greater catabolic activity on bone, but there is no evidence that they act differently than cortisol. Rather, it is probably because they are used in inappropriately high dosage.

The usual replacement dosages of these glucocorticoids are : hydrocortisone about 25 mg/day, cortisone acetate about 37.5 mg/day, prednisone about 5 mg/day, and dexamethasone about 0.5 mg/day. Glucocorticoid replacement in any patient must be carefully monitored and individualized.

By Dr. David Orth MD (November, 1996)