What symptoms and signs would a patient with a history of secondary adrenal insufficiency, recently discontinued from hydrocortisone (corticosteroid replacement therapy), exhibit if they were unable to produce the right amount of corticosteroids?

Symptoms and Signs of Inadequate Corticosteroid Production in Secondary Adrenal Insufficiency

If a patient with secondary adrenal insufficiency recently discontinued from hydrocortisone were unable to produce adequate corticosteroids, they would develop adrenal crisis—a life-threatening emergency requiring immediate recognition and treatment with IV hydrocortisone 100 mg and aggressive saline resuscitation. 1, 2

Acute Presentation: Adrenal Crisis

The most critical manifestation of inadequate corticosteroid production is adrenal crisis, which occurs at a rate of 6-8 episodes per 100 patient-years in those with secondary adrenal insufficiency 1. This is a medical emergency with high mortality if untreated 2:

Cardiovascular Manifestations

• Severe hypotension and shock with dehydration are hallmark features, often refractory to standard vasopressor therapy 2
• Unexplained collapse requiring immediate intervention 2
• Orthostatic hypotension (though this reflects mineralocorticoid deficiency more common in primary AI) 2

Gastrointestinal Symptoms

• Severe vomiting and/or diarrhea are common precipitating events and presenting symptoms 2
• Nausea occurs in 20-62% of patients, frequently accompanied by poor appetite and weight loss 2
• Severe abdominal pain with peritoneal irritation 2
• Morning nausea and lack of appetite are particularly characteristic 2

Neurological Manifestations

• Severe weakness, confusion, and altered mental status are not uncommon 2
• Loss of consciousness and coma in severe cases 2
• Lethargy and profound fatigue 2

Musculoskeletal Symptoms

• Muscle pain or cramps, often accompanied by abdominal pain 2

Chronic Symptoms of Under-Replacement

If the patient is not in acute crisis but simply under-replaced, they would exhibit 2:

• Daily fatigue and lethargy that is persistent and debilitating 2
• Poor appetite with progressive weight loss 2
• General and mental fatigue with decreased motivation 3
• Depressive symptoms 3
• Reduced physical functioning and vitality 3
• Cold intolerance 2
• Difficulty maintaining weight 2

Laboratory Abnormalities

Expected Findings in Secondary Adrenal Insufficiency

• Hyponatremia is present in 90% of newly diagnosed cases and can be indistinguishable from SIADH 2
• Hypoglycemia may occur, particularly in children 2
• Increased creatinine from prerenal renal failure 2
• Mild hypercalcemia sometimes occurs 2

Critical Distinction from Primary Adrenal Insufficiency

• Hyperkalemia is typically ABSENT in secondary adrenal insufficiency because the renin-angiotensin-aldosterone system remains intact 2
• Normal skin color (no hyperpigmentation) due to low ACTH, unlike primary adrenal insufficiency where hyperpigmentation is a distinguishing feature 2

Diagnostic Confirmation

If adrenal insufficiency is suspected after hydrocortisone discontinuation 2:

• Morning serum cortisol <250 nmol/L (<9 μg/dL) with low or inappropriately normal ACTH is diagnostic of secondary adrenal insufficiency 2
• Cosyntropin stimulation test with peak cortisol <500 nmol/L (<18 μg/dL) confirms the diagnosis 2
• However, treatment should NEVER be delayed for diagnostic procedures if the patient is clinically unstable 1, 2

Critical Pitfalls to Avoid

• The absence of hyperkalemia cannot rule out adrenal insufficiency—it occurs in only ~50% of cases overall and is typically absent in secondary AI 2
• Do not rely on electrolyte abnormalities alone; between 10-20% of patients have mild or moderate hypercalcemia, and some may have normal electrolytes 2
• Never delay treatment of suspected acute adrenal crisis for diagnostic testing—mortality is high if untreated 1, 2
• Laboratory confirmation should not be attempted in patients recently given corticosteroids until sufficient washout time has elapsed (typically 3 months for HPA axis recovery testing) 2

Immediate Management Protocol

If adrenal crisis is suspected 1, 2:

1. Administer 100 mg IV hydrocortisone immediately 1, 2
2. Infuse 0.9% saline at 1 L/hour (at least 2L total) 1, 2
3. Draw blood for cortisol and ACTH before treatment if possible, but do not delay treatment 1, 2
4. Continue hydrocortisone 200 mg/24 hours as continuous infusion or 50-100 mg IV every 6-8 hours 1, 4