What are the causes and management of adrenal insufficiency in a patient experiencing persistent vomiting?

Causes and Management of Adrenal Insufficiency in Persistent Vomiting

Causes of Adrenal Insufficiency

Adrenal insufficiency is classified into three categories: primary (adrenal gland destruction), secondary (pituitary/hypothalamic dysfunction), and iatrogenic (glucocorticoid-induced suppression). 1

Primary Adrenal Insufficiency (Addison's Disease)

• Autoimmune destruction accounts for approximately 85% of cases in Western populations 2
• Congenital adrenal hyperplasia is the most common cause in children, occurring in 1 in 15,000 live births 3
• Infectious causes include tuberculosis and fungal infections 1
• Pharmacological inhibition from high-dose azole antifungal therapy 1
• Adrenal hemorrhage or metastatic disease 2
• Surgical removal of adrenal cortical tissue 1

Secondary Adrenal Insufficiency

• Pituitary tumors, hemorrhage, or inflammatory conditions such as hypophysitis, sarcoidosis, or hemochromatosis 1
• Brain tumors and their treatment in children 3
• Medications suppressing ACTH production including opioids 1
• Radiation therapy or pituitary surgery 1

Iatrogenic (Glucocorticoid-Induced) Adrenal Insufficiency

• Chronic glucocorticoid therapy at doses ≥5 mg prednisolone equivalent for longer than 1 month causes HPA axis suppression 3
• This is the most common form of adrenal insufficiency despite primary and secondary forms being rare 1

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Why Vomiting is Critical in Adrenal Insufficiency

Gastroenteritis with vomiting is one of the most common precipitants of adrenal crisis, occurring in approximately half of patients who experience crisis. 3

Pathophysiology of Vomiting in This Context

• Vomiting prevents oral glucocorticoid absorption, leading to acute under-replacement during a period of increased physiological stress 3
• Nausea and vomiting occur in 20-62% of patients with adrenal insufficiency as baseline symptoms 4
• Persistent vomiting causes hypokalemia that masks the expected hyperkalemia of primary adrenal insufficiency, making diagnosis more challenging 2

Critical Electrolyte Pitfall

• Hyponatremia is present in 90% of newly diagnosed cases, but the absence of hyperkalemia cannot rule out adrenal insufficiency 2, 4
• Hyperkalemia occurs in only ~50% of cases, and when vomiting is present, gastrointestinal potassium losses cause hypokalemia instead 2

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Management Algorithm for Adrenal Insufficiency with Persistent Vomiting

Step 1: Immediate Recognition and Emergency Treatment

If the patient is clinically unstable (hypotension, altered mental status, shock), give 100 mg IV hydrocortisone immediately—do NOT delay for diagnostic testing. 3, 2

• Administer hydrocortisone 100 mg IV bolus immediately 3, 2, 5
• Infuse 1 liter of 0.9% normal saline over 1 hour, then continue at a slower rate for 24-48 hours 3, 2
• Draw blood for serum cortisol, ACTH, sodium, potassium, creatinine, and glucose before giving hydrocortisone if possible, but never delay treatment 3, 2
• If diagnosis is uncertain and you still want to perform testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 4

Step 2: Ongoing Stress-Dose Glucocorticoid Therapy

Continue hydrocortisone 100-300 mg/day as continuous IV infusion or divided doses every 6 hours until the patient can tolerate oral intake. 3

• For continuous infusion: 200 mg hydrocortisone per 24 hours 3
• For intermittent dosing: 100 mg IV/IM every 6 hours 3
• Continue IV therapy until vomiting resolves and the patient can reliably take oral medications 3

Step 3: Transition to Oral Therapy

When vomiting stops and oral intake is tolerated, taper to 2-3 times the maintenance dose for 48 hours to 1 week depending on illness severity. 3

• If usual dose was 10-5-5 mg hydrocortisone, double to 20-10-10 mg for 48 hours after minor illness or up to 1 week after major stress 3
• Resume maintenance dosing only when the patient is fully recovered 3

Step 4: Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Restart fludrocortisone 0.05-0.1 mg daily when hydrocortisone dose falls below 50 mg/day. 3, 6

• Mineralocorticoid replacement is NOT needed during high-dose IV hydrocortisone because 100 mg hydrocortisone saturates mineralocorticoid receptors 3
• Fludrocortisone is only required for primary adrenal insufficiency, not secondary or iatrogenic forms 3, 1
• Typical maintenance range is 50-200 mcg daily, adjusted based on blood pressure, salt craving, and electrolytes 4, 6

Step 5: Identify and Treat Precipitating Causes

Draw blood cultures and obtain imaging as indicated to diagnose bacterial or viral infections, which are common triggers. 3

• Common precipitants include gastroenteritis, fever, surgical stress, pregnancy, and emotional distress 3
• Treat underlying infections with appropriate antibiotics while continuing stress-dose steroids 3

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Diagnostic Confirmation (When Patient is Stable)

If the diagnosis of adrenal insufficiency is not yet established, perform morning cortisol and ACTH measurements followed by cosyntropin stimulation testing. 2, 4

Distinguishing Primary from Secondary Adrenal Insufficiency

• Primary adrenal insufficiency: Morning cortisol <250 nmol/L (<9 mcg/dL) with HIGH ACTH 2, 4
• Secondary adrenal insufficiency: Morning cortisol <400 nmol/L with LOW or inappropriately normal ACTH 2, 4

Cosyntropin Stimulation Test Protocol

• Administer 0.25 mg (250 mcg) cosyntropin IV or IM 2, 4
• Measure cortisol at baseline, 30 minutes, and 60 minutes 2, 4
• Peak cortisol <500 nmol/L (<18 mcg/dL) is diagnostic of adrenal insufficiency 2, 4
• Peak cortisol >550 nmol/L (>18-20 mcg/dL) excludes adrenal insufficiency 4

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Prevention of Future Crises

All patients with adrenal insufficiency must receive education on stress dosing, wear a medical alert bracelet, and carry injectable hydrocortisone 100 mg IM with self-injection training. 4, 1, 7

Patient Education Essentials

• Double or triple oral glucocorticoid dose during illness, fever, vomiting, or physical stress 4, 1
• Seek immediate medical attention if unable to keep oral medications down 7
• Carry a steroid emergency card and medical alert identification at all times 4, 7
• Have injectable hydrocortisone 100 mg available for self-administration or family member administration during vomiting or severe illness 1, 7

Common Pitfalls to Avoid

• Never rely on electrolyte abnormalities alone to diagnose or exclude adrenal insufficiency—10-20% of patients have normal electrolytes at presentation 4
• Do not assume absence of hyperkalemia rules out adrenal insufficiency—vomiting causes hypokalemia that masks the expected hyperkalemia 2
• Never delay treatment of suspected adrenal crisis for diagnostic procedures—mortality is high if untreated 3, 2, 4
• Do not forget to restart fludrocortisone when tapering hydrocortisone below 50 mg/day in primary adrenal insufficiency 3