What are the symptoms of adrenal insufficiency?

Symptoms of Adrenal Insufficiency

The hallmark symptoms of adrenal insufficiency include profound fatigue, unintentional weight loss, anorexia, postural hypotension, muscle and abdominal pain, nausea, vomiting, and hyponatremia, with primary adrenal insufficiency additionally characterized by salt craving and skin hyperpigmentation. 1, 2

Primary vs. Secondary Adrenal Insufficiency Symptoms

Primary Adrenal Insufficiency (Adrenal Gland Failure)

• Fatigue (50-95% of patients) 1
• Nausea and vomiting (20-62%) 1
• Anorexia and weight loss (43-73%) 1
• Postural hypotension 2
• Abdominal pain 2
• Muscle pain 2
• Distinctive features:
  • Skin hyperpigmentation (due to high ACTH levels) 3, 2
  • Salt craving (due to mineralocorticoid deficiency) 2
  • Electrolyte abnormalities (decreased sodium, increased potassium) 3

Secondary Adrenal Insufficiency (Pituitary Issues)

• Similar non-specific symptoms as primary:
  • Fatigue
  • Decreased appetite
  • Weight loss 3
• Key differences:
  • No hyperpigmentation (due to low ACTH levels) 3
  • Usually normal electrolytes 3
  • May have symptoms related to other pituitary hormone deficiencies

Laboratory Findings

Primary Adrenal Insufficiency

• Low morning cortisol (<5 μg/dL) 1
• High ACTH levels 3, 1
• Low DHEAS levels 1
• Electrolyte abnormalities (↓Na, ↑K) 3

Secondary Adrenal Insufficiency

• Low or intermediate morning cortisol (5-10 μg/dL) 1
• Low or low-normal ACTH levels 3, 1
• Low DHEAS levels 1
• Usually normal electrolytes 3

Adrenal Crisis

Adrenal crisis is a life-threatening emergency that can occur in patients with adrenal insufficiency, especially during times of stress or illness 1, 4. Symptoms include:

• Severe hypotension/shock 1
• Hyponatremia 1
• Altered mental status 1
• Severe abdominal pain, nausea, and vomiting 4
• Fever 4

Special Considerations

Glucocorticoid-Induced Adrenal Insufficiency

• Most common form of adrenal insufficiency 1, 5
• Symptoms may be masked by underlying condition 5
• Often unrecognized - only ≤1% of patients on glucocorticoids have adrenal testing recorded 5
• Should be suspected in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 1

Clinical Pitfalls

• Diagnosis is often delayed because initial presentation is non-specific 2
• Symptoms may overlap with many common conditions, leading to missed diagnosis 5
• More than 70% of cases are identified during acute hospital admission 5
• Physician awareness must be improved to avoid adrenal crisis 2

Diagnostic Approach

• Morning cortisol levels serve as an initial screening tool but are insufficient alone for definitive diagnosis 3
• Short ACTH stimulation test is the gold standard for confirming diagnosis 3
• Normal response: peak cortisol >18-20 μg/dL after cosyntropin stimulation 3
• Failure to reach this threshold indicates adrenal insufficiency 3

Early detection based on clinical suspicion is crucial to prevent progression to adrenal crisis, which can be fatal if not promptly treated 4.