What are the characteristic features and treatment of Addison's disease?

Characteristic Features and Treatment of Addison's Disease

Addison's disease requires lifelong replacement therapy with both glucocorticoids and mineralocorticoids to prevent potentially fatal adrenal crisis, with hydrocortisone 15-25 mg daily in divided doses and fludrocortisone 0.1 mg daily as the standard treatment regimen. 1, 2

Clinical Presentation

• Symptoms develop insidiously over months to years and include fatigue, nausea, poor appetite, weight loss, and increased pigmentation that often has an uneven distribution 1
• Hyperpigmentation of the skin is a characteristic feature, especially in areas subjected to friction, and can affect mucosal surfaces including the tongue and cheek 2, 3
• Laboratory findings typically include hyponatremia (present in 90% of newly diagnosed cases), hyperkalaemia (in approximately 50% of cases), and low serum cortisol with elevated ACTH levels 2, 4
• Neuropsychiatric manifestations including depression and psychosis can also occur 5

Diagnostic Approach

• Diagnosis follows a two-step approach, beginning with paired measurement of serum cortisol and plasma ACTH 1, 2
• Serum cortisol <250 nmol/L with elevated ACTH during acute illness is diagnostic 2
• In equivocal cases, a synacthen (tetracosactide) stimulation test is performed (0.25 mg IM or IV), with peak serum cortisol <500 nmol/L confirming the diagnosis 1, 2
• Once primary adrenal insufficiency is confirmed, etiologic diagnosis should be determined as it affects treatment decisions and follow-up 1
• Autoimmunity accounts for approximately 85% of diagnoses in Western Europe, confirmed by measuring 21-hydroxylase autoantibodies (21OH-Ab) 1
• Other causes include tuberculosis (look for adrenal calcifications on CT), adrenal hemorrhage, metastatic neoplasms, and genetic disorders such as adrenoleukodystrophy (screen males by measuring very long-chain fatty acids) 1, 5

Treatment Regimen

Glucocorticoid Replacement

• Hydrocortisone (HC) or cortisone acetate (CA) are the preferred glucocorticoids 1, 2
• Standard dosing: HC 15-25 mg daily in 2-3 divided doses, with first dose upon awakening and last dose not less than 6 hours before bedtime 1
• Cortisone acetate requires activation to hydrocortisone by hepatic 11β-hydroxysteroid dehydrogenase type 1 1
• Monitoring is primarily clinical rather than laboratory-based; symptoms of over-replacement include weight gain, insomnia, and peripheral edema 1, 2

Mineralocorticoid Replacement

• Fludrocortisone is indicated at a dose of 0.1 mg daily, although dosage ranging from 0.1 mg three times a week to 0.2 mg daily may be employed 6
• If transient hypertension develops, the dose should be reduced to 0.05 mg daily 6
• Patients should be advised to take salt and salty foods ad libitum 1

Management of Adrenal Crisis

• Adrenal crisis is a life-threatening emergency requiring immediate treatment 1, 2
• Treatment includes immediate administration of hydrocortisone 100 mg IV or IM, followed by 100 mg every 6-8 hours until recovery 1, 2
• Rapid infusion of isotonic (0.9%) sodium chloride solution, initially at 1 L/hour until hemodynamic improvement 1
• Blood should be drawn for diagnostic testing, but treatment should never be delayed for diagnostic procedures 1

Special Situations

• Surgery and invasive procedures require increased steroid doses according to the severity of the procedure 1
• For major surgery: 100 mg hydrocortisone IM just before anesthesia, then 100 mg every 6 hours until able to eat and drink 1
• For minor procedures: double oral dose for 24 hours, then return to normal dose 1
• Pregnancy may require small adjustments to hydrocortisone and fludrocortisone doses, particularly during the last trimester 1

Patient Education and Follow-up

• Patients should wear a Medic Alert bracelet and carry a steroid card to inform medical personnel of their condition 1, 2
• Education on increasing steroid doses during concurrent illnesses or injury is essential 1
• Annual follow-up should include assessment of health and well-being, measurement of weight and blood pressure, monitoring of serum electrolytes, and screening for development of new autoimmune disorders 1, 2
• Approximately half of patients with autoimmune PAI have other co-existing autoimmune diseases, commonly classified as polyendocrine syndromes 2

Emerging Therapies

• Modified-release hydrocortisone and continuous subcutaneous hydrocortisone infusion have been developed to better simulate physiological cortisol rhythm 7
• Some research has explored modifying the natural history of adrenal failure using ACTH stimulation and immunomodulatory therapies 7

With proper treatment, Addison's disease is a manageable chronic condition, though premature death from adrenal crises remains a risk if management guidelines are not strictly followed 2, 4.