How should I evaluate and manage an adult with suspected adrenal insufficiency presenting with fatigue, weight loss, abdominal pain, hyperpigmentation, hypotension, hyponatremia, hyperkalemia, or adrenal crisis?

Evaluation and Management of Suspected Adrenal Insufficiency in Adults

If you suspect adrenal insufficiency based on clinical presentation (fatigue, weight loss, hypotension, hyperpigmentation, hyponatremia), obtain early morning (8 AM) serum cortisol and plasma ACTH immediately, but never delay treatment if the patient is unstable—give IV hydrocortisone 100 mg and 0.9% saline at 1 L/hour first, then draw labs. 1, 2, 3

Initial Diagnostic Workup

First-Line Laboratory Tests

• Morning (8 AM) serum cortisol and plasma ACTH are your first-line tests 1, 3
• Basic metabolic panel (sodium, potassium, CO2, glucose) to assess for characteristic electrolyte abnormalities 1
• Draw these before giving hydrocortisone if the patient is stable enough to wait, but treatment takes absolute priority over diagnosis 1, 2

Interpreting Initial Results

Primary adrenal insufficiency:

• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH is diagnostic 1, 3
• Often accompanied by hyponatremia (90% of cases) and hyperkalemia (only 50% of cases) 1, 2
• Hyperpigmentation present due to elevated ACTH 2, 4

Secondary adrenal insufficiency:

• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH 1, 3
• Hyponatremia may be present, but hyperkalemia is absent 1
• No hyperpigmentation (low ACTH) 2

Critical pitfall: The absence of hyperkalemia cannot rule out adrenal insufficiency—it's only present in ~50% of cases 1, 2. Hyponatremia is present in 90% of newly diagnosed cases but can be indistinguishable from SIADH 1.

Confirmatory Testing: Cosyntropin Stimulation Test

When to Perform

• When morning cortisol is indeterminate (5-18 μg/dL) 1, 3
• To definitively confirm or exclude adrenal insufficiency 1
• Never delay this test if you need to treat suspected adrenal crisis 1, 2

Test Protocol

• Administer 0.25 mg (250 mcg) cosyntropin IV or IM 1, 3
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes 1
• Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency 1, 3
• Peak cortisol >550 nmol/L (>18-20 μg/dL) excludes adrenal insufficiency 1

Important Considerations

• Do not perform this test in patients currently taking corticosteroids—they will have false-positive results due to iatrogenic HPA suppression 1
• If you must treat before confirming diagnosis, use dexamethasone 4 mg IV instead of hydrocortisone, as it doesn't interfere with cortisol assays 1
• Exogenous steroids (prednisone, prednisolone, inhaled fluticasone) suppress the HPA axis and confound results 1

Etiologic Workup

For Primary Adrenal Insufficiency

1. Measure 21-hydroxylase autoantibodies first—autoimmunity accounts for ~85% of cases in Western populations 1, 4
2. If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tumor, tuberculosis, or other structural causes 1
3. In males with negative antibodies, assay very long-chain fatty acids (VLCFA) to check for adrenoleukodystrophy 1

For Secondary Adrenal Insufficiency

• Evaluate for pituitary pathology (tumors, hemorrhage, hypophysitis, sarcoidosis) 3
• Assess for other pituitary hormone deficiencies 1
• Consider history of opioid use, which suppresses corticotropin production 3

Emergency Management: Adrenal Crisis

Recognize the Clinical Picture

• Hypotension (often severe) and shock 2
• Severe vomiting and/or diarrhea 2
• Altered mental status, confusion, or coma 2
• Unexplained collapse 1, 2
• Abdominal pain with peritoneal irritation 2

Immediate Treatment Protocol

1. Give IV hydrocortisone 100 mg bolus immediately upon clinical suspicion—do not wait for lab results 1, 2, 3
2. Start 0.9% isotonic saline at 1 L over the first hour 2
3. Draw blood for cortisol, ACTH, electrolytes, creatinine, and glucose before treatment if possible, but never delay therapy 2

Subsequent Management

• Continue hydrocortisone 200 mg per 24 hours as continuous IV infusion OR 50 mg IV/IM every 6 hours 2
• Maintain slower isotonic saline infusion for 24-48 hours (total 3-4 liters over 24 hours) 2
• Monitor serum electrolytes frequently 2
• Do not add fludrocortisone during acute crisis—high-dose hydrocortisone provides adequate mineralocorticoid activity 2, 5

Transition to Maintenance

• Taper parenteral glucocorticoids over 1-3 days to oral therapy once the patient can tolerate oral medications 2
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 2, 5

Chronic Maintenance Therapy

Glucocorticoid Replacement

For primary or secondary adrenal insufficiency:

• Hydrocortisone 15-25 mg daily in divided doses (e.g., 10 mg at 7 AM, 5 mg at 12 PM, 2.5-5 mg at 4 PM) 1, 3, 6
• Alternative: Prednisone 3-5 mg daily 1, 3
• Hydrocortisone is preferred over long-acting steroids because it recreates the diurnal cortisol rhythm 1

Mineralocorticoid Replacement (Primary AI Only)

• Fludrocortisone 50-200 μg (0.05-0.2 mg) daily 1, 5, 3, 6
• Monitor adequacy by assessing salt cravings, orthostatic blood pressure, peripheral edema, and plasma renin activity 1, 5
• Unrestricted sodium salt intake is essential 1

Monitoring for Under-Replacement

• Orthostatic hypotension is an early cardinal feature—check both sitting/standing and supine blood pressure 2, 5
• Morning nausea and lack of appetite suggest under-replacement 1
• Lethargy, weight loss, increased pigmentation 1
• Chronic under-replacement with fludrocortisone predisposes to recurrent adrenal crises 2, 5

Stress Dosing and Patient Education

Sick Day Rules

• Double or triple the usual dose during minor illness, fever, or physical stress 1, 3
• For moderate stress: Hydrocortisone 30-50 mg total daily OR prednisone 20 mg daily 1
• For major stress/surgery: Hydrocortisone 100-150 mg daily 1

Emergency Preparedness

• Prescribe hydrocortisone 100 mg IM injection kit with self-injection training 1, 3
• Medical alert bracelet or necklace indicating adrenal insufficiency is mandatory 1, 2, 3
• Educate on warning signs of impending adrenal crisis 1

Critical Pitfall

When treating concurrent hypothyroidism and adrenal insufficiency, start corticosteroids several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1, 2

Special Considerations

Drug Interactions

Medications that increase hydrocortisone requirements:

• Anti-epileptics, rifampin, barbiturates (CYP3A4 inducers) 1

Medications that decrease hydrocortisone requirements:

• Grapefruit juice, liquorice (CYP3A4 inhibitors)—should be avoided 1

Medications that interfere with fludrocortisone:

• Diuretics, acetazolamide, NSAIDs 1

Annual Screening

• Thyroid function, diabetes, vitamin B12 deficiency 1
• Celiac disease (if frequent diarrhea) with tissue transglutaminase 2 autoantibodies 1
• Bone mineral density every 3-5 years 1

Mandatory Endocrine Consultation

• Newly diagnosed adrenal insufficiency 1
• Pre-operative planning 1
• Recurrent adrenal crises 1, 2
• Recovery protocols after prolonged steroid use 1