Glucocorticoid replacement for adrenal insufficiency

Patients with adrenal insufficiency require lifelong glucocorticoid replacement. The goal of therapy is to replicate the steroid exposure of adrenal cortisol synthesis and relieve symptoms of glucocorticoid deficiency, using the lowest effective glucocorticoid dose.

Long-term glucocorticoid therapy can reduce bone mineral density (BMD) and increase fracture risk; measure the patient’s baseline BMD and assess their fracture risk (see Risk factors for minimal-trauma fracture) at diagnosis. See also Monitoring of adrenal insufficiency for information about monitoring of BMD during treatment.

Hydrocortisone is the most commonly used glucocorticoid for adrenal insufficiency in both adults and children. Cortisone acetate is converted to hydrocortisone in the body and is a suitable alternative. Prednisolone and prednisone should not be used in children because they can cause growth suppression. In adults, prednisolone (or prednisone) is not usually used for initial therapy, but is sometimes used for maintenance therapy; its longer duration of effect allows once daily dosing, which is helpful if adherence is a concern. Dexamethasone is rarely used for replacement therapy because the available tablet strengths are not suitable for adrenal insufficiency dosing, and its long duration of effect increases the risk of overtreatment.

Adrenal cortisol synthesis can usually be approximated with hydrocortisone or cortisone acetate given twice daily in adults, while children usually require dosing three times daily. Some adults benefit from more frequent dosing (eg those who experience excessive evening fatigue).

Corticosteroid exposure in the evening is associated with adverse metabolic effects. To reduce these effects, the daily dose should be weighted towards the morning. In a patient taking a twice-daily regimen, approximately two-thirds of the daily dose should be taken in the morning immediately after waking, and one-third of the daily dose should be taken in the mid-afternoon. If three daily doses are required, they can be taken in the morning immediately after waking, in the middle of the day, and in the late afternoon (before 5 pm).

A suitable starting dose for an adult with adrenal insufficiency is:

A suitable starting dose for a child with primary adrenal insufficiency is:

In a child with adrenal insufficiency secondary to pituitary or hypothalamic disease, a lower glucocorticoid dose can be used. A suitable starting dose is:

The glucocorticoid dose should be adjusted in small increments, aiming for the lowest effective dose. Dose adjustments should be made under specialist guidance, based on clinical response; no one biomarker can be used to guide dosing. Dose requirements vary significantly among patients. Patients with adrenal insufficiency secondary to hypopituitarism often have a lower dose requirement than patients with primary adrenal insufficiency. See also Monitoring of adrenal insufficiency for signs of overtreatment or undertreatment.

Although no specific upper dose limit exists for glucocorticoid replacement, if the patient has persistent symptoms or requires a higher dose than expected, consider other factors that may be contributing to symptoms.

During illness and surgery, the glucocorticoid dose needs to be increased to simulate the normal increase in cortisol secretion that occurs in response to stress (see Glucocorticoid replacement during intercurrent illness and surgery).