Secondary adrenal insufficiency can result from insufficient stimulation of the adrenal glands due to inadequate secretion or synthesis of adrenocorticotropic hormone (ACTH). This can be caused by hypopituitarism, central nervous system injury (tumors, radiation, and surgery) or long-term glucocorticoid therapy. Glucocorticoids were introduced in the 1950s, and have been used for their anti-inflammatory and other pharmacological effects, and also as replacement therapy for adrenal insufficiency. However, chronic glucocorticoid use may lead to suppression of the hypothalamic pituitary adrenal axis through negative feedback. This may lead to secondary adrenal insufficiency. Typically, the hypothalamic pituitary adrenal axis recovers after cessation of glucocorticoids, but the timing of recovery can be variable and can take anywhere from 6-12 months. Understanding the effect of exogenous glucocorticoids on the hypothalamic pituitary adrenal axis, recovery of the axis, and tests used to assess the recovery, are crucial to avoid prescribing unnecessary steroid replacement or missing a critical diagnosis with detrimental consequences.
During minor illness (., flu or fever >38° C [° F]) the hydrocortisone dose should be doubled for 2 or 3 days. The inability to ingest hydrocortisone tablets warrants parenteral administration. Most patients can be educated to self administer hydrocortisone, 100 mg IM, and reduce the risk of an emergency room visit. Hydrocortisone, 75 mg/day, provides adequate glucocorticoid coverage for outpatient surgery. Parenteral hydrocortisone, 150 to 200 mg/day (in three or four divided doses), is needed for major surgery, with a rapid taper to normal replacement during the recovery. Patients taking more than 100 mg hydrocortisone/day do not need any additional mineralocorticoid replacement. All patients should wear some form of identification indicating their adrenal insufficiency status.
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.