Adrenal insufficiency results from inadequate adrenocortical function, which may be due to destruction of the adrenal cortex (primary adrenal insufficiency; Addison’s disease), deficient pituitary ACTH secretion (secondary adrenal insufficiency), or deficient hypothalamic secretion of CRH or other ACTH secretagogues (tertiary adrenal insufficiency). Primary and secondary adrenal insufficiency related to natural causes are uncommon, whereas iatrogenic, tertiary adrenal insufficiency caused by suppression of HPA function by glucocorticoid administration is common.

Glucocorticoid treatment may not suppress the HPA axis at all, or it may cause central suppression or complete adrenal gland atrophy. Supraphysiologic glucocorticoid doses inhibit both CRH production in the hypothalamus and ACTH production in the pituitary gland. When this inhibition lasts longer than the duration of the glucocorticoid exposure, it is called adrenal suppression.

Since the introduction of glucocorticoids in the treatment of rheumatoid arthritis in 1949, the therapeutic applications of these drugs were greatly broadened to encompass a large number of nonendocrine and endocrine diseases (1-4). The glucocorticoid-induced adrenal suppression, when glucocorticoids are used in supraphysiologic doses, renders the adrenal glands unable to generate sufficient cortisol if glucocorticoid treatment is abruptly stopped and the patient develops glucocorticoid deficiency manifestations. The true prevalence of clinically significant adrenal insufficiency is not known since physicians usually discontinue high-dose glucocorticoids gradually to allow recovery of the HPA axis.

Some of the risk factors for HPA axis suppression are clearly defined, whereas others are less certain (5, 6). Systemic glucocorticoid therapy is more likely to suppress the HPA axis than compartmentalized use of glucocorticoids with the possible exception of intra-articular steroids (4, 7). Systemic glucocorticoid potency is also known to correlate with risk for adrenal insufficiency (4, 7, 8). Glucocorticoid treatment in endocrine and nonendocrine disorders, the side effects of these medications, their concomitant use and interactions with other drugs, adrenal suppression and the glucocorticoid withdrawal syndrome are discussed in detail here.