Symptoms of Adrenal Insufficiency
The most common symptoms of adrenal insufficiency include fatigue (50-95%), nausea and vomiting (20-62%), anorexia and weight loss (43-73%), orthostatic hypotension, muscle weakness, and salt craving (in primary adrenal insufficiency). 1, 2
Clinical Presentation by System
General Symptoms
- Profound fatigue and weakness
- Unintentional weight loss
- Anorexia (loss of appetite)
- Dizziness, especially when standing (orthostatic hypotension)
Gastrointestinal Symptoms
- Nausea and vomiting
- Abdominal pain
- Salt craving (primarily in primary adrenal insufficiency)
Cardiovascular Symptoms
- Orthostatic hypotension (blood pressure drop when standing)
- Hypotension
- Risk of cardiovascular collapse in adrenal crisis
Dermatologic Symptoms
- Hyperpigmentation of skin (in primary adrenal insufficiency)
- Thin, fragile skin (with long-term glucocorticoid therapy)
Neurological Symptoms
- Headache
- Confusion or altered mental status (especially during crisis)
- Irritability
Metabolic Abnormalities
- Hyponatremia (low sodium)
- Hyperkalemia (high potassium, in primary adrenal insufficiency)
- Hypoglycemia
Differences Between Primary and Secondary Adrenal Insufficiency
Primary Adrenal Insufficiency (Addison's Disease)
- Hyperpigmentation of skin (due to elevated ACTH)
- Salt craving
- Electrolyte abnormalities: low sodium, high potassium
- More severe symptoms due to deficiency of all adrenocortical hormones
Secondary Adrenal Insufficiency
- No hyperpigmentation (ACTH is low)
- Normal electrolytes (mineralocorticoid function preserved)
- May have other pituitary hormone deficiencies
- Symptoms may be more subtle initially
Symptoms of Adrenal Crisis (Medical Emergency)
- Severe hypotension or shock
- Severe abdominal pain
- Severe nausea and vomiting
- Confusion or altered mental status
- Fever
- Hypoglycemia
- Severe electrolyte abnormalities 2
Special Clinical Considerations
Timing of Symptom Onset
The median time to onset of endocrine toxicities in patients receiving immune checkpoint inhibitors is 14.5 weeks (range 1.5-130 weeks) 3. This highlights the importance of monitoring patients on these medications.
Diagnostic Pitfalls
- Symptoms are often nonspecific, leading to delayed diagnosis 1
- Approximately 10% of patients with primary adrenal insufficiency may present with normal cortisol concentrations but elevated ACTH levels 4
- When multiple pituitary hormones are deficient, hydrocortisone must be replaced before thyroid hormone to avoid precipitating an adrenal crisis 3
High-Risk Situations
- Patients with known adrenal insufficiency are at risk during:
- Intercurrent illness
- Surgery or procedures
- Physical stress
- Hot weather conditions
- Intense exercise 2
Importance of Early Recognition
Adrenal insufficiency continues to be a cause of significant morbidity and mortality, especially when diagnosis is delayed or during intercurrent illness when glucocorticoid doses are not appropriately increased 5. All patients should be educated about symptoms, wear medical alert identification, carry a steroid alert card, and have an emergency hydrocortisone injection kit 2.
Remember that the presentation of adrenal insufficiency can vary dramatically, posing a major diagnostic challenge that requires high clinical suspicion, especially in patients with risk factors such as autoimmune disorders, history of steroid use, or pituitary disease 6.