When should adrenal insufficiency be considered in a patient with hypotension?

When to Consider Adrenal Insufficiency in Hypotension

Adrenal insufficiency should be considered immediately in any patient with unexplained hypotension that does not respond to fluid resuscitation, particularly in those with a history of chronic steroid use (≥20 mg/day prednisone equivalent for ≥3 weeks), recent steroid discontinuation, or critical illness with shock requiring vasopressors. 1

High-Risk Clinical Scenarios Requiring Immediate Consideration

Patients on Chronic Steroid Therapy

• Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise. 1
• Patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids are at particularly high risk. 2
• In the perioperative setting, if unexplained, fluid-unresponsive hypotension occurs, immediately administer 100 mg IV hydrocortisone as a rescue dose, followed by 50 mg IV hydrocortisone every 6 hours. 1, 3

Vasopressor-Resistant Hypotension

• Hypotension requiring high-dose vasopressors or multiple vasopressor agents that remains refractory to treatment is a critical indication to consider adrenal insufficiency. 1, 4
• In critically ill patients with cirrhosis and refractory shock, consider screening for adrenal insufficiency or empiric hydrocortisone 50 mg IV q6h or 200-mg infusion for 7 days. 1
• Vasopressor-resistant hypotension attributed to adrenal insufficiency may respond to stress-dose hydrocortisone alone, potentially avoiding high doses of other lymphocytotoxic corticosteroids. 1

Critical Illness and Septic Shock

• Adrenal insufficiency is common and underdiagnosed in critically ill patients, with hypotension refractory to fluids and requiring vasopressors being the most common presentation in the ICU. 4
• In patients with septic shock or acute decompensation, relative adrenal insufficiency occurs in approximately 49% of hospitalized patients with cirrhosis and is associated with significantly higher 90-day mortality. 1

Key Clinical Features That Should Trigger Suspicion

Classic Presentation Triad

• Unexplained collapse, hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal insufficiency. 1
• Hyperpigmentation (in primary adrenal insufficiency), hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion. 1

Laboratory Abnormalities

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases, but the absence of hyperkalemia cannot rule out the diagnosis as it occurs in only ~50% of cases. 1, 5
• The classic combination of hyponatremia and hyperkalemia is not reliable for diagnosis, as sodium levels are often only marginally reduced. 1
• In the presence of severe vomiting, hypokalaemia and alkalosis may be present instead of the expected hyperkalemia. 1

Important Pitfall to Avoid

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—between 10-20% of patients have mild or moderate hypercalcemia at presentation, and some may have normal electrolytes. 1

Diagnostic Approach When Adrenal Insufficiency is Suspected

Immediate Action in Unstable Patients

• Treatment of suspected acute adrenal insufficiency should NEVER be delayed by diagnostic procedures. 1, 5
• If adrenal crisis is suspected, immediately administer IV hydrocortisone 100 mg bolus and infuse 0.9% saline at 1 L/hour. 5
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy to obtain these samples. 5

Diagnostic Testing in Stable Patients

• Paired measurement of early morning (8 AM) serum cortisol and plasma ACTH is the first-line diagnostic test. 1, 5, 2
• Serum cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in the presence of acute illness is diagnostic of primary adrenal insufficiency. 1, 5
• Serum cortisol <400 nmol/L with elevated ACTH in acute illness raises strong suspicion of primary adrenal insufficiency. 1

Confirmatory Testing

• In equivocal cases, a cosyntropin (tetracosactide) stimulation test with 0.25 mg IM or IV should be performed, with peak serum cortisol <500 nmol/L (<18 μg/dL) at 30-60 minutes being diagnostic. 1, 5
• The cosyntropin stimulation test is the gold standard for confirming adrenal insufficiency when initial results are indeterminate. 5

Special Populations and Contexts

Hemodialysis Patients

• Unexplained hypotension in patients on hemodialysis with a history of corticosteroid therapy should prompt consideration of adrenal insufficiency as a possible cause. 6

Distinguishing from SIADH

• Adrenal insufficiency must be excluded before diagnosing SIADH, as both conditions present with euvolemic hypo-osmolar hyponatremia and can be clinically indistinguishable. 5
• The standard 0.25 mg cosyntropin stimulation test is medically necessary to rule out adrenal insufficiency in patients with hypo-osmolality and hyponatremia. 5

Patients with Pituitary Disease

• In secondary adrenal insufficiency (pituitary origin), morning cortisol is typically 5-10 μg/dL with low or inappropriately normal ACTH. 5, 2
• The cosyntropin test can give false normal results in secondary adrenal insufficiency, so if strongly suspected, insulin hypoglycemia or metyrapone testing may be required. 7

Practical Algorithm for Clinical Decision-Making

Step 1: Identify High-Risk Patients

• History of chronic steroid use (≥20 mg/day prednisone ≥3 weeks) 1
• Recent steroid taper or discontinuation 2
• Pituitary disease or surgery 7
• Critical illness with shock 4

Step 2: Recognize Triggering Clinical Scenario

• Unexplained hypotension unresponsive to fluid resuscitation 1, 4
• Vasopressor-resistant shock 1, 4
• Collapse with vomiting/diarrhea 1
• Perioperative hypotension 1

Step 3: Immediate Management

• If unstable: Give 100 mg IV hydrocortisone immediately, do NOT delay for testing 1, 5
• If stable: Obtain morning cortisol and ACTH before treatment 5, 2

Step 4: Interpret Results

• Cortisol <250 nmol/L + high ACTH = primary adrenal insufficiency (treat immediately) 1, 5
• Cortisol <400 nmol/L + high ACTH = strong suspicion (treat empirically) 1
• Equivocal results = perform cosyntropin stimulation test 1, 5

Critical Pitfalls to Avoid

• Never wait for diagnostic test results to treat suspected adrenal crisis—mortality is high if untreated. 1, 5
• Do not assume normal electrolytes exclude adrenal insufficiency—hyperkalemia is absent in 50% of cases. 1, 5
• Do not confuse adrenal insufficiency with SIADH—both present with hyponatremia and require different treatments. 5
• Exogenous steroid use (oral prednisolone, dexamethasone, inhaled fluticasone) can confound interpretation of low cortisol levels. 1, 7
• In patients with both adrenal insufficiency and hypothyroidism, start corticosteroids several days before thyroid hormone replacement to prevent precipitating adrenal crisis. 5