What are the presenting features and management of a secondary adrenal crisis in a patient with a history of steroid use or pituitary disease?

Secondary Adrenal Crisis: Presenting Features

Secondary adrenal crisis presents with hypotension, severe weakness, nausea/vomiting, abdominal pain, hyponatremia, and altered mental status—but notably WITHOUT hyperkalemia or hyperpigmentation, distinguishing it from primary adrenal insufficiency. 1, 2, 3

Key Clinical Features

Cardinal Presenting Symptoms

• Severe weakness and fatigue occur in 50-95% of patients, often progressing to profound lethargy or inability to stand 4, 2
• Nausea and vomiting present in 20-62% of cases, frequently accompanied by severe abdominal pain that may mimic an acute abdomen with peritoneal irritation 1, 4, 2
• Hypotension and shock are hallmark features, with blood pressure often refractory to fluid resuscitation alone until glucocorticoids are administered 1, 2, 4
• Altered mental status ranging from confusion to loss of consciousness and coma is not uncommon in severe presentations 1, 2

Laboratory Abnormalities

• Hyponatremia is present in 90% of newly diagnosed cases, making it the most sensitive laboratory marker 2, 3
• Hyperkalemia is ABSENT in secondary adrenal insufficiency because aldosterone secretion remains intact (unlike primary adrenal insufficiency where it occurs in ~50% of cases) 2, 3
• Hypoglycemia may occur, particularly during acute illness or in children 1, 4
• Prerenal azotemia with elevated creatinine reflects volume depletion and hypoperfusion 1

Distinguishing Features from Primary Adrenal Insufficiency

• No hyperpigmentation because ACTH levels are low or inappropriately normal (not elevated) 3, 2
• No hyperkalemia or significant salt wasting due to preserved mineralocorticoid function 3, 2
• Hyponatremia without hyperkalemia is the characteristic electrolyte pattern 2

Common Precipitating Factors

• Gastroenteritis with vomiting/diarrhea is the most frequent trigger, accounting for approximately half of adrenal crises 1, 5
• Infections including fever, pneumonia, or any systemic infection 1, 5
• Surgical procedures or major trauma requiring increased cortisol production 1, 5
• Medication errors or omissions during hospitalization, including failure to increase glucocorticoid doses during stress 1
• Abrupt discontinuation or tapering of chronic glucocorticoid therapy in patients with steroid-induced adrenal insufficiency 4, 6
• Drug interactions with CYP3A4 inducers (rifampin, phenytoin, carbamazepine, modafinil) that accelerate hydrocortisone clearance 7, 8

High-Risk Clinical Scenarios

• Any patient taking ≥20 mg/day prednisone or equivalent for ≥3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise 2, 3
• Vasopressor-resistant hypotension requiring multiple agents or high doses should immediately raise suspicion for adrenal crisis 2
• Unexplained collapse with gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) in patients with known pituitary disease or chronic steroid use 2

Critical Management Principles

Immediate Treatment (Do NOT Delay for Diagnostic Testing)

• Treatment of suspected acute adrenal crisis must NEVER be delayed for diagnostic procedures if the patient is clinically unstable 1, 2, 3, 7
• Administer 100 mg IV hydrocortisone immediately as a bolus, followed by continuous infusion of 200 mg/24 hours or 50-100 mg IV every 6-8 hours 1, 9
• Rapid IV administration of 0.9% saline at 1 L/hour (at least 2-3 liters total in first few hours) to correct volume depletion and hypotension 1, 2
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay therapy to obtain samples 1, 2

Alternative Approach if Diagnosis Uncertain

• If you need to treat suspected crisis but still want to perform diagnostic testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 2
• However, dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 2

Common Pitfalls to Avoid

• Do not rely on electrolyte abnormalities alone to make or exclude the diagnosis—hyperkalemia is absent in secondary adrenal insufficiency, and some patients may have normal electrolytes 2, 3
• Do not wait for cortisol results if the patient is hemodynamically unstable—mortality is high if treatment is delayed 2, 5
• Do not assume normal or even high plasma cortisol levels exclude adrenal crisis in physiologically stressed patients (concept of relative adrenal insufficiency) 1
• Do not dismiss patient observations about warning signs of under-replacement, especially in patients with longstanding diagnosis who are accustomed to managing their condition 1

Patient Education and Prevention

• All patients with adrenal insufficiency require education on stress dosing: double or triple the usual dose during illness, fever, or physical stress 2, 9
• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training for use during severe vomiting or inability to take oral medications 2, 4
• Medical alert bracelet or necklace indicating adrenal insufficiency is mandatory to trigger appropriate emergency treatment 1, 2, 4
• Notify all healthcare providers about adrenal insufficiency before any surgery or procedures, with endocrine consultation for stress-dose planning 2, 9