What is the relationship between intractable vomiting and serum cortisol levels in a patient with severe and prolonged vomiting?

Intractable Vomiting and Serum Cortisol: A Critical Diagnostic Relationship

Intractable vomiting should immediately prompt measurement of serum cortisol and ACTH to rule out primary adrenal insufficiency (PAI), as this life-threatening condition presents with vomiting in the context of inappropriately low cortisol levels and requires urgent glucocorticoid replacement. 1

The Bidirectional Cortisol-Vomiting Relationship

Low Cortisol Causing Vomiting (Primary Concern)

Primary adrenal insufficiency must be considered in all patients with unexplained vomiting, as this represents a reversible and potentially fatal cause. 1

• Diagnostic thresholds in acute illness: Serum cortisol <250 nmol/L with elevated ACTH is diagnostic of PAI; cortisol <400 nmol/L with elevated ACTH raises strong suspicion and warrants immediate treatment. 1

• Critical caveat: In acutely ill patients (including those with severe vomiting), cortisol levels within the "normal range" may still be inappropriately low for the stress state, representing relative adrenal insufficiency. 1

• Treatment must never be delayed: If PAI is suspected based on clinical presentation (vomiting, hypotension, hyponatremia), glucocorticoid replacement should be initiated immediately without waiting for diagnostic confirmation. 1

• Complete symptom resolution: Patients with intractable vomiting due to adrenal insufficiency respond dramatically to glucocorticoid replacement with complete improvement. 2

Electrolyte Confounders in Severe Vomiting

A critical diagnostic pitfall exists: severe vomiting itself can mask the typical electrolyte pattern of adrenal insufficiency. 1

• In PAI without vomiting, expect hyponatremia (90% of cases) and hyperkalemia (50% of cases) due to aldosterone deficiency. 1

• However, in the presence of severe vomiting, hypokalemia and metabolic alkalosis may be present instead of the expected hyperkalemia, as gastric losses override the aldosterone deficiency. 1

• This means you cannot rule out adrenal insufficiency based on normal or low potassium levels when vomiting is severe. 1

Cortisol as an Endogenous Antiemetic

Endogenous cortisol exerts antiemetic effects, and lower baseline cortisol levels predict more severe chemotherapy-induced nausea and vomiting. 3

• Patients with low pre-treatment cortisol excretion experience more severe cisplatin-induced nausea and vomiting despite ondansetron therapy. 3

• Exogenous dexamethasone provides greater antiemetic benefit in patients with low endogenous cortisol production. 3

• This explains why corticosteroids (dexamethasone 10-20 mg IV) are recommended as second-line therapy for intractable vomiting in combination with ondansetron. 4

Cyclic Vomiting and Cortisol Surges

In cyclic vomiting syndrome (CVS), paradoxical elevations in ACTH and cortisol can precede and accompany vomiting episodes, representing a distinct pathophysiological pattern. 5, 6

• Case reports document 10-fold increases in 24-hour urinary cortisol levels during CVS episodes, with abnormal elevations in ACTH, serum cortisol, or urinary cortisol always preceding vomiting episodes. 5

• These cortisol surges in CVS represent periodic ACTH discharge rather than adrenal insufficiency, and high-dose dexamethasone suppression does not abort the clinical symptoms. 5, 6

• This pattern is thought to reflect hypothalamic-pituitary dysregulation rather than primary adrenal pathology. 5, 6

Practical Diagnostic Algorithm

When evaluating intractable vomiting, measure paired serum cortisol and plasma ACTH immediately, before initiating antiemetic therapy. 1

1. If cortisol <250 nmol/L with elevated ACTH: Diagnose PAI and initiate hydrocortisone 100 mg IV immediately. 1

2. If cortisol 250-400 nmol/L with elevated ACTH in acute illness: Strongly suspect PAI and initiate empiric glucocorticoid therapy while pursuing confirmatory testing. 1

3. If cortisol is inappropriately normal for the stress state: Consider relative adrenal insufficiency, particularly in patients with sepsis or critical illness. 1

4. Check electrolytes but do not rely on them: Obtain sodium and potassium, but remember that severe vomiting can cause hypokalemia and alkalosis even in PAI, masking the typical hyperkalemia. 1

5. If PAI is confirmed: Measure 21-hydroxylase autoantibodies to determine etiology; if negative, obtain CT imaging and check very long-chain fatty acids in males. 1

Critical Pitfalls to Avoid

• Never delay glucocorticoid replacement for diagnostic testing if clinical suspicion for adrenal crisis is high based on vomiting, hypotension, and hyponatremia. 1

• Do not rule out adrenal insufficiency based on normal or low potassium levels when severe vomiting is present, as gastric losses override aldosterone deficiency. 1

• Do not interpret "normal range" cortisol as reassuring in acutely ill patients with severe vomiting, as the level may be inappropriately low for the stress state. 1

• Recognize that exogenous steroids confound interpretation: Oral prednisolone, dexamethasone, and even inhaled fluticasone can suppress measured cortisol levels. 1

• In cyclic vomiting with elevated cortisol: This represents a distinct entity (periodic ACTH discharge) that does not respond to dexamethasone suppression and requires different management (consider ketorolac or CVS-specific prophylaxis). 5, 6