What is adrenal insufficiency?

Adrenal Insufficiency: Definition and Management

Adrenal insufficiency is a condition characterized by inadequate production of adrenal cortical hormones, primarily cortisol and often aldosterone, which can lead to life-threatening consequences if untreated. 1, 2

Types of Adrenal Insufficiency

• Primary adrenal insufficiency (Addison's disease): Results from direct damage to the adrenal cortex, characterized by low cortisol, high ACTH, hyponatremia, and hyperkalemia due to loss of both cortisol and aldosterone production 1
• Secondary adrenal insufficiency: Caused by pituitary disorders leading to inadequate ACTH production, resulting in cortisol deficiency but normal aldosterone levels 3
• Tertiary adrenal insufficiency: Results from hypothalamic dysfunction affecting CRH production 4
• Glucocorticoid-induced adrenal insufficiency: The most common form, occurring after withdrawal from supraphysiological doses of exogenous glucocorticoids 3

Epidemiology

• Primary and secondary adrenal insufficiency are rare, affecting less than 279 per 1 million individuals 3
• In Europe, autoimmunity accounts for approximately 85% of primary adrenal insufficiency cases 1
• Other causes include tuberculosis, adrenal hemorrhage, and genetic disorders 1

Clinical Presentation

• Symptoms typically develop insidiously over months to years 1
• Common symptoms include:
  • Fatigue (50-95% of patients) 3
  • Nausea and vomiting (20-62%) 3
  • Anorexia and weight loss (43-73%) 3
  • Salt craving (particularly in primary adrenal insufficiency) 1
  • Hyperpigmentation (in primary adrenal insufficiency) 3
  • Hypotension and orthostatic changes 2
  • Hypoglycemia (particularly in neonates and during stress) 5

Laboratory Findings

• Primary adrenal insufficiency:

  • Low morning cortisol (<5 μg/dL) with elevated ACTH 3
  • Hyponatremia (present in 90% of newly diagnosed cases) 1
  • Hyperkalemia (in approximately 50% of cases) 1
  • Low DHEAS levels 3

• Secondary adrenal insufficiency:

  • Low or intermediate morning cortisol (5-10 μg/dL) 3
  • Low or low-normal ACTH and DHEAS levels 3

Diagnostic Approach

• Initial evaluation includes morning (8 AM) serum cortisol and plasma ACTH measurements 2
• Basic metabolic panel to assess sodium, potassium, CO2, and glucose 2
• In acute illness, cortisol <250 nmol/L (9 μg/dL) with elevated ACTH is diagnostic of primary adrenal insufficiency 2
• For intermediate results, consider ACTH stimulation test (measure cortisol before and 60 minutes after administration of 250 μg cosyntropin) 3
• For primary adrenal insufficiency, measure 21-hydroxylase autoantibodies to determine etiology 2
• If antibodies are negative, obtain adrenal CT imaging to evaluate for hemorrhage, tumor, or infection 2

Treatment

• Hormone replacement therapy: Lifelong treatment is required to prevent potentially fatal adrenal crisis 1

  • Glucocorticoid replacement: Hydrocortisone (15-25 mg daily in divided doses) or prednisone (3-5 mg daily) 3
  • Mineralocorticoid replacement: Fludrocortisone (0.1 mg daily) for primary adrenal insufficiency 1

• Dose adjustment: Glucocorticoid dosage should be adjusted based on clinical assessment rather than laboratory values 1

• Management of adrenal crisis:

  • Immediate administration of hydrocortisone 100 mg IV or IM, followed by 100 mg every 6-8 hours until recovery 2
  • Rapid infusion of isotonic (0.9%) sodium chloride solution at an initial rate of 1 L/hour until hemodynamic improvement 2
  • Identify and treat the underlying precipitant (e.g., infection) 2

Patient Education and Prevention of Adrenal Crisis

• All patients should:
  • Wear a medical alert bracelet and carry a steroid card 1
  • Receive education on increasing steroid doses during illness, injury, or stress 1
  • Have access to injectable glucocorticoids for emergency use 3
  • Avoid abrupt discontinuation of glucocorticoid therapy 6

Prognosis and Monitoring

• With proper treatment, adrenal insufficiency is a manageable chronic condition 1
• However, premature death from adrenal crises remains a risk 1
• Annual follow-up should include:
  • Assessment of health and well-being
  • Measurement of weight and blood pressure
  • Monitoring of serum electrolytes
  • Screening for development of new autoimmune disorders
  • Assessment for complications of glucocorticoid therapy 1

Common Pitfalls to Avoid

• Delaying treatment in suspected acute adrenal insufficiency while waiting for test results 2
• Failing to provide patient education on stress dosing and adrenal crisis prevention 1
• Abrupt discontinuation of glucocorticoid therapy in patients on long-term treatment 6