Part of “CHAPTER 76 – ADRENOCORTICAL INSUFFICIENCY“

Secondary adrenal insufficiency has three causes: adrenal suppression after exogenous glucocorticoid or ACTH administration, adrenal suppression after the correction of endogenous glucocorticoid hypersecretion, and abnormalities of the hypothalamus or pituitary gland leading to ACTH deficiency.

The histologic appearance of the adrenal glands in secondary adrenal insufficiency varies from normal-appearing to simple atrophy of the cortex with a normal medulla.

Adrenal suppression by exogenous glucocorticoids is the most common cause of secondary adrenal insufficiency.23,24 and 25 The frequent use of glucocorticoids to treat inflammatory disorders, such as dermatitis, arthritis, and hepatitis, is the underlying reason. Supraphysiologic doses of glucocorticoids given long enough suppress hypothalamic corticotropin-releasing hormone production and the ability of the anterior pituitary gland to respond to this hormone. The degree of adrenal suppression depends on three variables: dosage, schedule of administration, and duration of administration. Significant adrenal suppression is rarely seen with dosages of hydrocortisone (or its equivalent) of <15 mg/m² per day. A divided dosage schedule is more suppressive than is a once-a-day or once-every-other-day schedule. Finally, the longer the duration of administration, the greater the likelihood of suppression. Treatment periods of <14 days, for example, rarely lead to clinically important adrenal suppression, whereas treatment periods long enough to allow the emergence of the signs of Cushing syndrome usually are associated with clinically significant suppression of adrenal function. Secondary adrenal insufficiency can become manifest shortly after the cessation of corticosteroid therapy or months later in a stressful setting such as after an injury or a surgical procedure. The duration of impairment can be as long as 1 year after the correction of hypercortisolism.26 These findings have led to the conservative practice of replacing glucocorticoid before an anticipated stress in any patient who has received supraphysio-logic dosages of glucocorticoids within the past year. An alternative, and more satisfactory, practice is to test the functional capacity of the adrenal glands directly with ACTH and to base the need for glucocorticoid supplementation on the results (see Chap. 78 for an extensive discussion of exogenous corticosteroid administration and its complications).27