How is Addison's disease diagnosed and treated?

Diagnosis and Treatment of Addison's Disease

Addison's disease should be diagnosed through a two-step approach involving initial measurement of serum cortisol and ACTH levels, followed by confirmatory testing with a cosyntropin stimulation test, and treated with lifelong replacement of both glucocorticoids (hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoids (fludrocortisone 50-200 μg daily). 1, 2

Diagnostic Approach

Initial Evaluation

• Paired measurement of serum cortisol and plasma ACTH is the first diagnostic step - low cortisol with elevated ACTH suggests primary adrenal insufficiency 2
• Serum cortisol <250 nmol/L with elevated ACTH during acute illness is diagnostic of Addison's disease 2
• Common laboratory findings include hyponatremia (90% of cases), hyperkalemia (50% of cases), and hypoglycemia (especially in children) 2, 1

Confirmatory Testing

• When diagnosis is uncertain, perform a cosyntropin (synacthen) stimulation test by administering 0.25 mg cosyntropin IM or IV 1
• Measure serum cortisol at 30 and/or 60 minutes after administration 1
• Normal response: cortisol should exceed 550 nmol/L (or 500 nmol/L according to some guidelines) 1, 2
• Failure to reach this threshold confirms adrenal insufficiency 1

Etiologic Diagnosis

• Once primary adrenal insufficiency is confirmed, determine the underlying cause 1
• Measure 21-hydroxylase antibodies (21OH-Ab) to diagnose autoimmune etiology (accounts for 85% of cases in Western countries) 1
• Consider adrenal imaging (CT) if antibodies are negative to evaluate for other causes such as tuberculosis, hemorrhage, or tumors 1

Treatment Approach

Glucocorticoid Replacement

• Hydrocortisone is the preferred glucocorticoid replacement, given in divided doses 1, 2
• Standard dosing: 15-25 mg daily in 2-3 divided doses (first dose upon waking, last dose at least 6 hours before bedtime) 1, 2
• Children require 6-10 mg/m² of body surface area 1
• Use the lowest effective dose that maintains health and well-being 1

Mineralocorticoid Replacement

• Fludrocortisone 50-200 μg once daily is the standard mineralocorticoid replacement 1, 3
• FDA-approved dosing is 0.1 mg daily, though doses may range from 0.1 mg three times weekly to 0.2 mg daily 3
• Children and younger adults may require higher doses 1
• If hypertension develops, reduce dose to 0.05 mg daily but do not discontinue 1, 3
• Patients should consume salt and salty foods freely and avoid licorice and grapefruit juice 1

Management of Adrenal Crisis

Recognition

• Symptoms include malaise, fatigue, nausea, vomiting, abdominal pain, muscle pain/cramps, dehydration, hypotension, and shock 1
• Laboratory findings include hyponatremia, hyperkalemia, increased creatinine, hypoglycemia, and sometimes mild hypercalcemia 1

Emergency Treatment

• Do not delay treatment for diagnostic procedures - if adrenal crisis is suspected, treat immediately 1
• Administer hydrocortisone 100 mg IV/IM immediately, followed by 100 mg every 6-8 hours until recovered 1, 2
• Provide rapid IV infusion of isotonic (0.9%) saline at an initial rate of 1 L/hour until hemodynamic improvement 1
• Identify and treat the underlying precipitant (often infection) 1

Special Situations

Surgery and Medical Procedures

• Major surgery: 100 mg hydrocortisone IM before anesthesia, continue 100 mg IM every 6 hours until oral intake is possible 1
• Minor surgery: 100 mg hydrocortisone IM before procedure, double oral dose for 24 hours afterward 1
• Labor and delivery: 100 mg hydrocortisone IM at onset of labor, double oral dose for 24-48 hours after delivery 1

Patient Education

• All patients need education on increasing steroid doses during illness (stress dosing) 1, 2
• Patients should wear a medical alert bracelet for adrenal insufficiency 1, 2
• Provide supplies for self-injection of parenteral hydrocortisone for emergency use 1

Follow-up Care

• Review patients at least annually 1
• Monitor weight, blood pressure, and serum electrolytes 1
• Screen for development of other autoimmune disorders, particularly hypothyroidism 1
• Assess for complications of glucocorticoid therapy, including bone mineral density every 3-5 years 1

Common Pitfalls and Caveats

• Do not delay treatment of suspected adrenal crisis for diagnostic testing 1
• Diagnosis may be challenging in patients already on corticosteroids for other conditions 1
• Symptoms of Addison's disease develop insidiously and may be nonspecific, leading to delayed diagnosis 4, 5
• The first presentation of Addison's disease may be an adrenal crisis triggered by stress such as infection 6
• Diagnosis can be particularly challenging in patients with end-stage renal disease due to overlapping symptoms 7