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Treatment of chronic primary adrenal insufficiency in adults

1. Glucocorticoid replacement

Hydrocortisone 15 to 25 mg orally in two or three divided doses (largest dose in morning upon awakening; typically 10 mg upon arising in morning, 5 mg early afternoon, 2.5 mg late afternoon) or

Prednisone 5 mg (range: 2.5 to 7.5 mg) orally at bedtime; or

Dexamethasone 0.75 mg (range: 0.25 to 0.75 mg) orally at bedtime

Monitor clinical symptoms and morning plasma ACTH.

2. Mineralocorticoid replacement^*

Fludrocortisone 0.1 mg (range: 0.05 to 0.2 mg) orally.

Liberal salt intake.

Monitor lying and standing blood pressure and pulse, edema, serum potassium, and plasma renin activity.

3. Androgen replacement

Dehydroepiandrosterone (DHEA)^¶ initially 25 to 50 mg orally (only in women with impaired mood or sense of well-being despite optimal glucocorticoid and mineralocorticoid replacement).

4. Patient education

Educate patient about the disease, how to manage minor illnesses and major stresses, and how to inject dexamethasone or other glucocorticoid intramuscularly or subcutaneously.

Refer to UpToDate patient education topics on adrenal insufficiency (Addison's disease).

5. Emergency precautions

Obtain medical alert bracelet/necklace, Emergency Medical Information Card, and prefilled syringes containing dexamethasone 4 mg in 1 mL saline.

6. Treatment of minor febrile illness or stress

Increase glucocorticoid dose two- to threefold for the few days of illness. Do not change mineralocorticoid dose.

Patient is instructed to contact clinician if illness worsens or persists for more than three days.

No extra supplementation is needed for most uncomplicated, outpatient dental procedures under local anesthesia.

Glucocorticoid supplement for surgical stress:

Minor (eg, herniorrhaphy): hydrocortisone 25 mg IV (or equivalent) on day of procedure
Moderate (eg, orthopedic surgery): hydrocortisone 50 to 75 mg IV (or equivalent) on day of surgery and postoperative day 1
Major (eg, cardiac bypass): hydrocortisone 100 to 150 mg IV (or equivalent) in two or three divided doses on day of surgery and postoperative days 1 and 2

Then return to usual daily glucocorticoid dose.

General anesthesia or IV sedation should not be performed in the office setting.

7. Emergency treatment of severe stress or trauma

Each patient should have an injectable glucocorticoid (eg, 4 mg vials of dexamethasone or 100 mg vials of hydrocortisone) and vials of sterile 0.9% normal saline and syringes.

Instruct patient/caregivers on how to reconstitute the vial and to inject entire dose intramuscularly or subcutaneously in event of severe stress or trauma and get medical help immediately after injection.

ACTH: corticotropin; IV; intravenously.
* Hydrocortisone 20 mg and prednisone 50 mg provide a mineralocorticoid effect that is approximately equivalent to 0.1 mg of fludrocortisone, so fludrocortisone replacement (if needed) must be decreased appropriately. Dexamethasone lacks mineralocorticoid effect.
¶ DHEA is available in the United States and some other countries as a nonprescription dietary supplement, and these products are not well regulated for potency or purity.

Courtesy of Lynette Nieman, MD, with additional data from Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016; 101:364.

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