When should primary adrenal insufficiency (Addison's disease) be considered in the differential diagnosis of abdominal pain?

When to Consider Primary Adrenal Insufficiency in Abdominal Pain Presentations

Primary adrenal insufficiency (Addison's disease) should be in your differential for any patient presenting with abdominal pain accompanied by unexplained collapse, hypotension, vomiting, or diarrhea—particularly when associated with hyperpigmentation, hyponatremia, hyperkalemia, acidosis, or hypoglycemia. 1, 2

Key Clinical Scenarios That Should Trigger Suspicion

High-Risk Presentations

• Abdominal pain with unexplained collapse or syncope – this combination is a red flag for adrenal crisis 2
• Abdominal pain with peritoneal irritation in the absence of clear surgical pathology 1
• Severe abdominal pain accompanied by profound hypotension or shock that seems disproportionate to other findings 1
• Abdominal pain with severe vomiting that may indicate impending or established adrenal crisis 2

Supporting Clinical Features

• Hyperpigmentation – a distinguishing feature caused by elevated ACTH levels that should immediately raise suspicion when present with abdominal complaints 2
• Postural hypotension resulting from volume depletion due to aldosterone loss 2
• Profound fatigue and muscle pain or cramps accompanying the abdominal symptoms 1, 3
• Unintentional weight loss and anorexia in the weeks or months preceding presentation 3
• Salt craving – patients with primary adrenal insufficiency characteristically crave salt 3

Laboratory Abnormalities That Strengthen the Diagnosis

Electrolyte Disturbances

• Hyponatremia is present in 90% of newly presenting cases, though often only marginally reduced 1, 4, 2
• Hyperkalemia occurs in approximately 50% of patients at diagnosis due to aldosterone deficiency 1, 4, 2

Critical Caveat

The classic combination of hyponatremia and hyperkalemia is NOT always present and is not a reliable marker for diagnosis – sodium levels are often only marginally reduced, and potassium may be normal or even low 1, 2. In the presence of severe vomiting, you may paradoxically see hypokalemia and alkalosis instead of the expected hyperkalemia 1, 2.

Additional Laboratory Clues

• Hypoglycemia – more common in children but can occur in adults, with hypoglycemic seizures possible 1, 2
• Mild to moderate hypercalcemia in 10-20% of patients at presentation 1, 2
• Acidosis 1, 2
• Elevated creatinine from prerenal renal failure 1
• Anemia, mild eosinophilia, lymphocytosis, and elevated liver transaminases may be present 1, 2

Practical Diagnostic Approach

When Abdominal Pain Presentation Raises Suspicion

1. Draw blood immediately for serum cortisol, plasma ACTH, sodium, potassium, creatinine, urea, and glucose before initiating treatment 1
2. Do NOT delay treatment for diagnostic procedures if adrenal crisis is suspected 1, 2
3. Definitive diagnosis requires paired measurement of serum cortisol and plasma ACTH – a cortisol <250 nmol/L with elevated ACTH in the presence of acute illness is diagnostic 4

Common Pitfalls to Avoid

• Dismissing the diagnosis because electrolytes are "normal" – remember that the classic hyponatremia/hyperkalemia combination is absent in many cases 1, 2
• Waiting for diagnostic confirmation before treating – if adrenal crisis is suspected, give hydrocortisone 100 mg IV bolus immediately with 1 L of 0.9% saline over one hour 1, 4, 5
• Misinterpreting cortisol levels – exogenous steroid use (oral prednisolone, dexamethasone) and inhaled steroids (fluticasone) may confound interpretation of low serum cortisol levels 1, 2
• Overlooking the diagnosis in patients with vomiting and hypokalemia – severe vomiting can mask the expected hyperkalemia 1, 2

Why This Matters for Morbidity and Mortality

Adrenal crisis is life-threatening and occurs in approximately 50% of patients with adrenal insufficiency after diagnosis 3. Premature death from adrenal crises remains a significant problem despite available treatment 1. The diagnosis is frequently delayed because initial presentations are non-specific, leading to misdiagnosis and potentially fatal outcomes 3, 6, 7, 8.

Abdominal pain with peritoneal irritation is a recognized manifestation of adrenal crisis 1, and patients may be mistakenly taken to surgery for presumed acute abdomen when they actually need immediate glucocorticoid replacement. Physician awareness must be improved to avoid adrenal crisis 3.