What is the initial management of a patient with suspected primary adrenal insufficiency (Addison's disease)?

Initial Management of Primary Adrenal Insufficiency (Addison's Disease)

Immediate Treatment Protocol

If adrenal crisis is suspected clinically (hypotension, collapse, vomiting, altered mental status), immediately administer hydrocortisone 100 mg IV bolus plus 0.9% saline infusion at 1 L/hour without waiting for laboratory confirmation. 1, 2 Delaying treatment for diagnostic procedures increases mortality and is never acceptable. 1, 3

Pre-Treatment Blood Draw (If Patient Stable)

• Draw early-morning (8 AM) serum cortisol, ACTH, and DHEAS before initiating treatment, but never delay emergency treatment to obtain these samples. 2, 4
• Obtain basic metabolic panel (sodium, potassium, glucose) to assess for hyponatremia (present in 90% of cases) and hyperkalemia (present in 50% of cases). 1, 2

Chronic Replacement Therapy

Glucocorticoid Replacement

Start hydrocortisone 15-25 mg daily in 2-3 divided doses, with the last dose at least 6 hours before bedtime. 1 The typical regimen is 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM to approximate physiological cortisol secretion. 3 Alternative effective regimens include 15+5 mg, 10+10 mg, or 10+5+5 mg. 3

• Cortisone acetate 18.75-31.25 mg daily (or 25-37.5 mg daily per alternative source) is an acceptable alternative to hydrocortisone. 1, 2
• Prednisone 3-5 mg daily may be considered in select patients who experience marked fluctuations in energy over the day. 3, 4

Mineralocorticoid Replacement (Essential in Primary AI)

Start fludrocortisone 50-200 µg as a single daily dose. 1, 5 The FDA-approved dosing is 0.1 mg daily, with a range of 0.1 mg three times weekly to 0.2 mg daily. 5 Children and younger adults may require higher doses up to 500 µg daily. 1

• Monitor adequacy by assessing salt cravings, orthostatic blood pressure, and peripheral edema. 3
• Adjust based on blood pressure, volume status, sodium levels, and plasma renin activity. 3
• Critical pitfall: Under-replacement with mineralocorticoids is common and predisposes to recurrent adrenal crises. 2

Diagnostic Confirmation (After Treatment Initiated)

Cosyntropin Stimulation Test

• Administer 0.25 mg (250 mcg) cosyntropin IV or IM. 3, 2
• Measure serum cortisol at baseline and at 30 and/or 60 minutes post-administration. 3
• Diagnostic criteria: Peak cortisol <500-550 nmol/L (<18-20 μg/dL) confirms adrenal insufficiency; >550 nmol/L excludes it. 3, 2

Etiologic Workup

• Test for 21-hydroxylase autoantibodies (21OH-Ab), which are positive in ~85% of autoimmune Addison's disease cases. 1, 2
• If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tumor, tuberculosis, or infiltrative processes. 3, 2

Critical Patient Education and Safety Measures

All patients must receive the following immediately upon diagnosis:

• Medical alert identification jewelry (bracelet or necklace) indicating adrenal insufficiency. 1, 4
• Steroid emergency card warning about acute glucocorticoid replacement needs. 1, 6
• Emergency injectable hydrocortisone 100 mg IM kit with self-injection training. 1, 4
• Stress dosing instructions: Double the usual daily dose for 1-2 days during minor stress (fever, minor illness). 1, 2

Screening for Associated Autoimmune Conditions

Annual screening is mandatory because patients with autoimmune adrenal insufficiency are at high risk for additional autoimmune diseases. 1

• Thyroid function tests (TSH, free T4, TPO antibodies) annually. 1, 2
• Plasma glucose and HbA1c annually to detect diabetes mellitus. 1, 2
• Vitamin B12 levels annually. 2
• Screen for celiac disease with tissue transglutaminase 2 autoantibodies and total IgA if frequent or episodic diarrhea is present. 3

Critical Pitfall to Avoid

Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with concurrent hypothyroidism, as this can precipitate adrenal crisis. 1, 3, 2 Corticosteroids must be started several days before initiating thyroid hormone. 3

Follow-Up Monitoring

• Annual visits to assess symptoms, weight, blood pressure, and serum electrolytes. 1
• Evaluate for signs of under-replacement (lethargy, nausea, poor appetite, weight loss, increased pigmentation) or over-replacement. 1, 3
• Consider morning cortisol day curve if rapid cortisol disappearance is suspected. 1