What is adrenal insufficiency?

Adrenal Insufficiency

Adrenal insufficiency is a disorder characterized by inadequate production of adrenal hormones, primarily cortisol, which can be life-threatening if not properly diagnosed and treated. It is categorized as primary (originating in the adrenal glands), secondary (due to pituitary dysfunction), or tertiary/glucocorticoid-induced (from hypothalamic disorders or exogenous steroid use) 1.

Types and Prevalence

Primary Adrenal Insufficiency

• Involves deficiency of all adrenocortical hormones (cortisol AND aldosterone)
• Causes include autoimmune destruction, congenital adrenal hyperplasia, infections (tuberculosis, fungal), and surgical removal of adrenal tissue 1
• Affects approximately 1 in 8-10,000 in the general population 2

Secondary Adrenal Insufficiency

• Results from inadequate ACTH production by the pituitary gland
• Cortisol deficiency occurs, but aldosterone production remains intact
• Affects approximately 1 in 10,000 children 2

Glucocorticoid-Induced Adrenal Insufficiency

• Most common form of adrenal insufficiency
• Occurs in approximately 7 in 1,000 people on long-term oral corticosteroid therapy
• Can occur with all routes of steroid administration (oral, inhaled, topical, intranasal, intra-articular) 2

Clinical Presentation

Common Symptoms

• Fatigue (50-95% of cases)
• Nausea and vomiting (20-62%)
• Anorexia and weight loss (43-73%)
• Postural hypotension
• Muscle and abdominal pain
• Hyponatremia 1, 3

Distinguishing Features

• Primary adrenal insufficiency: Skin hyperpigmentation, salt craving, both cortisol and aldosterone deficiency 3
• Secondary adrenal insufficiency: No hyperpigmentation, normal aldosterone production 4

Diagnosis

Laboratory Testing

1. Morning cortisol and ACTH levels:

   • Primary AI: Low cortisol (<5 μg/dL), high ACTH
   • Secondary AI: Low cortisol, low or normal ACTH 1

2. Confirmatory testing:

   • Cosyntropin (Synacthen) stimulation test: Measure cortisol before and 60 minutes after 250 μg cosyntropin administration
   • Insulin tolerance test (gold standard for secondary AI) 5

3. Electrolyte abnormalities:

   • Primary AI: Low sodium, high potassium
   • Secondary AI: Generally normal electrolytes 4

Management

Hormone Replacement

1. Glucocorticoid replacement:

   • Hydrocortisone is the preferred glucocorticoid (10-20 mg morning, 5-10 mg afternoon)
   • Typical daily dose: 15-25 mg hydrocortisone or 3-5 mg prednisone 4, 1

2. Mineralocorticoid replacement:

   • Required only for primary adrenal insufficiency
   • Fludrocortisone 0.05-0.3 mg daily 1

Stress Dosing

• Patients must increase glucocorticoid doses during illness, procedures, or stress
• For major surgery: Hydrocortisone 100 mg IV at induction followed by continuous IV infusion of 200 mg/24h 2
• For minor procedures: Double normal hydrocortisone dose 2

Patient Education

• All patients should:
  • Wear a medical alert bracelet
  • Carry a steroid card
  • Have injectable glucocorticoids available (hydrocortisone 100 mg IM)
  • Receive education on stress dosing and emergency administration 4, 3

Adrenal Crisis Management

Adrenal crisis is a life-threatening emergency requiring immediate treatment:

• Immediate hydrocortisone 100 mg IV bolus
• Followed by 100-300 mg/day as continuous infusion or divided doses every 6 hours
• Rapid IV administration of isotonic saline 4
• Failure to recognize and treat adrenal crisis can be fatal 4

Monitoring

• Regular assessment of clinical symptoms
• Weight and blood pressure monitoring
• Serum electrolyte measurements
• Morning cortisol levels
• Annual consultation to assess replacement adequacy 4

Common Pitfalls

1. Delayed diagnosis due to non-specific symptoms - maintain high clinical suspicion
2. Inadequate stress dosing during illness or procedures - clear instructions are essential
3. Failure to distinguish between primary and secondary AI - treatment differs, particularly regarding mineralocorticoid replacement
4. Inadequate patient education about crisis prevention - approximately 50% of patients experience adrenal crisis after diagnosis 3
5. Overlooking glucocorticoid-induced AI in patients on steroid therapy - even inhaled steroids can cause HPA axis suppression 2

Remember that despite optimal replacement therapy, patients with adrenal insufficiency often experience reduced quality of life, decreased work capacity, and increased mortality compared to the general population 3.