What is Addison's disease (Adrenal insufficiency)?

From the Guidelines

Addison disease should be managed with lifelong hormone replacement therapy, including glucocorticoids (typically hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoids (fludrocortisone 0.05-0.2 mg daily), as well as education on stress dosing, emergency injections, and medical alert systems to prevent life-threatening adrenal crisis. The treatment of Addison disease involves replacing the deficient hormones with glucocorticoids and mineralocorticoids. According to the most recent and highest quality study 1, the preferred choice of glucocorticoid treatment is hydrocortisone (15-25 mg daily in divided doses) or prednisone (5-7.5 mg daily). Mineralocorticoid replacement is typically achieved with fludrocortisone (0.05-0.2 mg daily).

Key Components of Management

• Glucocorticoid replacement: hydrocortisone (15-25 mg daily in divided doses) or prednisone (5-7.5 mg daily) 1
• Mineralocorticoid replacement: fludrocortisone (0.05-0.2 mg daily) 1
• Education on stress dosing for sick days, use of emergency steroid injectables, and when to seek medical attention for impending adrenal crisis 1
• Medical alert systems, such as a bracelet or necklace, to trigger stress dose corticosteroids by emergency medical personnel 1

Monitoring and Adjustments

Regular monitoring of electrolytes, blood pressure, and symptoms is essential to adjust medication dosages. The disease results from autoimmune destruction of the adrenal cortex in about 70-90% of cases, with symptoms including fatigue, weakness, weight loss, salt cravings, hyperpigmentation, low blood pressure, and electrolyte imbalances. Without proper treatment, Addison disease can lead to life-threatening adrenal crisis, but with appropriate hormone replacement, patients can lead normal, healthy lives.

Additional Considerations

• Patients should be educated on the importance of stress dosing during illness, injury, or surgery to prevent adrenal crisis 1
• Endocrine consultation should be part of planning before surgery or high-stress treatments 1
• Laboratory confirmation of adrenal insufficiency should not be attempted in patients given high-dose corticosteroids for other conditions until treatment is ready to be discontinued 1

From the Research

Definition and Symptoms of Addison Disease

• Addison disease, also known as primary adrenal insufficiency, is a rare and potentially life-threatening condition characterized by the deficiency of glucocorticoids, mineralocorticoids, and adrenal androgens 2, 3.
• The symptoms of Addison disease can be subtle and may include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving 2, 3, 4.
• Acute adrenal crisis is a life-threatening condition that can occur in patients with Addison disease, characterized by orthostatic hypotension, fever, and hypoglycemia 2.

Diagnosis of Addison Disease

• The diagnosis of Addison disease is often delayed due to the nonspecific symptoms and signs, and a high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis 3, 4.
• The diagnosis can be confirmed by a cosyntropin stimulation test, which measures the response of the adrenal glands to adrenocorticotropic hormone (ACTH) 3.
• Laboratory tests, such as measurement of basal plasma cortisol, ACTH, and renin levels, can also help establish a diagnosis of Addison disease 2, 4.

Treatment of Addison Disease

• The treatment of Addison disease involves replacement of the deficient hormones, including mineralocorticoids and glucocorticoids 5, 6, 3.
• The starting doses of glucocorticoids should be 15-20 mg for hydrocortisone or 20-30 mg for cortisone acetate, divided into two or three doses, and preferentially weight-adjusted 5.
• Mineralocorticoid replacement, such as fludrocortisone 0.05-0.20 mg once daily, is also necessary 5.
• New treatment modalities, such as modified-released hydrocortisone and continuous subcutaneous hydrocortisone infusion, have recently been developed and offer the potential for closer simulation of the physiological serum cortisol rhythm 6.