Kind of steroid used and glucocorticoid potency. The synthetic analogs of glucocorticoids are much better tolerated as anti-inflammatory agents because they cause significantly less sodium retention at supraphysiologic doses than hydrocortisone and cortisone acetate (6, 8). Glucocorticoid potency (Table 1) correlates positively with risk for adrenal insufficiency (4, 8). Thus, hydrocortisone and cortisone acetate are the least potent and, therefore, least suppressive agents. Prednisone, prednisolone, methylprednisolone and triamcinolone are moderately suppressive, and dexamethasone suppresses ACTH the longest.

Systemic vs compartmental therapy. Systemic glucocorticoid therapy is more likely to suppress the HPA axis than are intra-articular, inhalational, or topical glucocorticoids (4).

Alternate day therapy. There is evidence that patients are at lower risk for adrenal insufficiency if they can take glucocorticoids on alternate days from the outset or if they can convert to alternate-day therapy before the HPA axis is suppressed (6, 55).

Once-a-day dosing in the morning or mimicking normal diurnal cortisol rhythms. Since evening doses of glucocorticoids tend to suppress the normal early morning surge of ACTH secretion (56), it is better, whenever possible, to treat patients with a single morning dose. Once-a-day dosing is usually feasible for prednisone, triamcinolone and dexamethasone. The short-acting hydrocortisone and cortisone acetate are usually given twice a day, at waking and around 5 PM. To mimic normal diurnal cortisol rhythms, the morning dose is two thirds, and the afternoon dose one third of the total daily dose.

Duration and cumulative dose of glucocorticoid treatment. Although traditionally the duration of glucocorticoid therapy and the cumulative dose of glucocorticoid received have been considered as predictive of the likelihood of HPA axis suppression, several studies suggest that they only roughly predict HPA axis suppression (6, 57, 58). Adrenal insufficiency is extremely rare in patients treated for 1 week or less (25, 26).