Signs and Symptoms of Adrenal Insufficiency
The diagnosis of adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting or diarrhea, along with hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia. 1
Common Clinical Presentations
General Symptoms
- Fatigue (50-95% of patients) 2
- Profound weakness
- Unintentional weight loss (43-73% of patients) 2
- Anorexia
- Postural hypotension
Gastrointestinal Symptoms
- Nausea and vomiting (20-62% of patients) 2
- Abdominal pain
- Salt craving (primarily in primary adrenal insufficiency) 3
Dermatological Signs
- Hyperpigmentation (in primary adrenal insufficiency)
- Most noticeable in skin creases, pressure points, and mucous membranes
- Due to increased ACTH levels
Cardiovascular Signs
- Hypotension
- Orthostatic hypotension
- Reduced cardiac output
- Risk of cardiovascular collapse in adrenal crisis
Laboratory Abnormalities
- Hyponatremia (present in 90% of newly diagnosed cases) 1
- Hyperkalemia (present in approximately 50% of patients) 1
- Hypoglycemia (more common in children than adults) 1, 4
- Mild to moderate hypercalcemia (10-20% of patients) 1
- Anemia
- Mild eosinophilia
- Lymphocytosis
- Increased liver transaminases 1
Differences Between Primary and Secondary Adrenal Insufficiency
Primary Adrenal Insufficiency (Addison's Disease)
- Hyperpigmentation (due to increased ACTH)
- More severe electrolyte disturbances (hyponatremia and hyperkalemia)
- Salt craving
- Low cortisol with elevated ACTH levels 2
- Low aldosterone and DHEAS levels 1
Secondary Adrenal Insufficiency
- No hyperpigmentation
- Less severe or absent electrolyte abnormalities
- Low cortisol with low or inappropriately normal ACTH levels 2
- TSH levels typically in range of 4-10 IU/L 1
Adrenal Crisis Presentation
Adrenal crisis is a life-threatening emergency characterized by:
- Severe hypotension or shock
- Acute abdominal pain
- Vomiting and diarrhea
- Altered mental status
- Fever
- Severe electrolyte abnormalities
- Can be fatal if untreated 5, 6
Special Considerations
In Children
- More prone to hypoglycemia than adults
- May present with hypoglycemic seizures 1, 7
- Failure to thrive
- Delayed puberty
During Illness or Stress
- Worsening of all symptoms
- Increased risk of adrenal crisis
- Inability to mount appropriate stress response 5
Diagnostic Approach
- Morning paired cortisol and ACTH levels are the initial diagnostic tests 5
- Serum cortisol <250 nmol/L with increased ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
- In equivocal cases, synacthen (tetracosactide) stimulation test with peak serum cortisol <500 nmol/L is diagnostic 1
Important Pitfalls to Avoid
- Delaying treatment of suspected acute adrenal insufficiency for diagnostic procedures 1
- Overlooking adrenal insufficiency due to non-specific symptoms
- Failing to recognize that severe vomiting may cause hypokalaemia and alkalosis rather than the expected hyperkalemia and acidosis 1
- Misinterpreting normal cortisol levels in stressed patients (may be inappropriately low for the disease state) 1
- Overlooking the confounding effect of exogenous steroid use on cortisol levels 1
Early recognition of these signs and symptoms is crucial to prevent adrenal crisis, which continues to be associated with significant morbidity and mortality despite available treatments 3, 6.