What is Addison's disease (Adrenal insufficiency)?

From the Guidelines

Addison's disease should be treated with hormone replacement therapy, typically with oral hydrocortisone (15-25 mg daily divided into 2-3 doses) to replace cortisol, and fludrocortisone (50-200 µg daily) to replace aldosterone if needed, as recommended by the most recent consensus statement 1. The diagnosis of primary adrenal insufficiency (PAI) should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion of PAI 1. The treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures, and the diagnostic test for primary PAI should be paired measurement of serum cortisol and plasma ACTH 1. Some key points to consider in the management of Addison's disease include:

• Patients should wear Medic Alert identification jewelry and carry a steroid/alert card, and receive sufficient education to manage daily medications and situations of minor to moderate concurrent illnesses 1.
• The lowest dose of hydrocortisone compatible with health and a sense of well-being should be used, and most patients with primary adrenal insufficiency should take 15–25 mg of hydrocortisone daily in split doses 1.
• Most patients with PAI should take 50–200 µg fludrocortisone as a single daily dose, and children and younger adults may require higher doses 1.
• Adrenal crisis should be treated immediately with iv or im hydrocortisone, 100 mg followed by 100 mg 6–8 hourly until recovered, and isotonic (0.9%) sodium chloride solution should usually be administered 1. Regular monitoring with blood tests and physician follow-ups is essential to adjust medication doses, and patients should be reviewed at least annually, with assessment of health and well-being, measurement of weight, blood pressure, and serum electrolytes 1.

From the FDA Drug Label

In Addison’s disease, the combination of fludrocortisone acetate tablets with a glucocorticoid such as hydrocortisone or cortisone provides substitution therapy approximating normal adrenal activity with minimal risks of unwanted effects. The usual dose is 0.1 mg of fludrocortisone acetate tablets daily, although dosage ranging from 0.1 mg three times a week to 0. 2 mg daily has been employed. Fludrocortisone acetate tablets are preferably administered in conjunction with cortisone (10 mg to 37. 5 mg daily in divided doses) or hydrocortisone (10 mg to 30 mg daily in divided doses). Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease

Addison's Disease Treatment:

• The recommended treatment for Addison's disease is a combination of fludrocortisone acetate tablets and a glucocorticoid, such as hydrocortisone or cortisone.
• The usual dose of fludrocortisone acetate tablets is 0.1 mg daily, with a range of 0.1 mg three times a week to 0.2 mg daily.
• Fludrocortisone acetate tablets should be administered in conjunction with cortisone (10 mg to 37.5 mg daily) or hydrocortisone (10 mg to 30 mg daily) 2, 2.

From the Research

Definition and Symptoms of Addison's Disease

• Addison's disease, also known as primary adrenal insufficiency, is a condition where the adrenal glands do not produce enough glucocorticoid and mineralocorticoid hormones 3.
• Symptoms of Addison's disease include orthostatic hypotension, fever, and hypoglycemia in acute cases, and malaise, anorexia, diarrhea, weight loss, joint and back pain in chronic cases 3.
• Cutaneous manifestations of Addison's disease include darkening of the skin, especially in sun-exposed areas, and hyperpigmentation of the palmar creases, frictional surfaces, and oral mucosa 3.

Diagnosis of Addison's Disease

• Measurement of basal plasma cortisol is an insensitive screening test for Addison's disease 3.
• Synthetic adrenocorticotropin 1-24 can be used as a dynamic test to diagnose Addison's disease 3.
• Elevated plasma levels of adrenocorticotropin and renin confirm the diagnosis of Addison's disease 3.

Treatment of Addison's Disease

• Treatment of Addison's disease involves replacement of the deficient hormones, including glucocorticoids and mineralocorticoids 4, 5, 3.
• Patients with Addison's disease require mineralocorticoid replacement, typically with fludrocortisone 0.05-0.20 mg once daily 4.
• 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 4.
• New treatment modalities, such as timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion, offer the potential for closer simulation of the physiological serum cortisol rhythm 4, 5.

Management and Quality of Life

• Optimum steroid replacement and patient education are vital for good quality of life and to prevent acute adrenal crisis in Addison's disease 6.
• Patients with Addison's disease may require adjustments to their treatment regimen to achieve adequate sodium and water balance, and to prevent undertreatment with fludrocortisone 7.
• Recent research has indicated increased mortality and impaired health-related quality of life (HRQoL) in patients with Addison's disease, despite conventional treatment 4.