Symptoms of Adrenal Insufficiency
Adrenal insufficiency presents with a constellation of symptoms including fatigue, weakness, weight loss, anorexia, nausea, vomiting, abdominal pain, hypotension, salt craving, and hyperpigmentation of the skin in primary adrenal insufficiency. 1
Common Clinical Presentations
General Symptoms
- Profound fatigue (50-95% of cases) 2
- Weakness
- Unintentional weight loss (43-73% of cases) 2
- Decreased appetite (anorexia)
- Dizziness, especially when standing (orthostatic symptoms)
Gastrointestinal Symptoms
- Nausea and vomiting (20-62% of cases) 2
- Abdominal pain
- Salt craving (specific to primary adrenal insufficiency)
Skin Changes
- Hyperpigmentation (darkening of the skin, particularly in skin folds, pressure points, and mucous membranes) - specific to primary adrenal insufficiency due to elevated ACTH levels 1
- Vitiligo (may be present in autoimmune causes)
Cardiovascular Symptoms
- Hypotension
- Orthostatic hypotension (drop in blood pressure upon standing)
- Dizziness or fainting
Psychological Symptoms
- Irritability
- Depression
- Poor concentration
- Mental changes
Laboratory Findings
Primary Adrenal Insufficiency
- Hyponatremia (low sodium) - present in approximately 90% of cases 1
- Hyperkalemia (high potassium) - present in approximately 50% of cases 1
- Low morning cortisol (<5 μg/dL) 2
- High ACTH levels 1
- Low aldosterone levels
- High renin levels
Secondary Adrenal Insufficiency
- Hyponatremia may be present
- Normal potassium levels
- Low morning cortisol
- Low or low-normal ACTH levels 2
- Normal aldosterone levels (typically)
Symptoms by Severity
Mild to Moderate Symptoms
- Fatigue and weakness
- Anorexia and weight loss
- Nausea
- Abdominal discomfort
- Hyperpigmentation (in primary adrenal insufficiency)
Severe Symptoms (Adrenal Crisis)
- Severe hypotension or shock
- Severe abdominal pain, nausea, and vomiting
- Confusion or altered mental status
- Fever
- Hypoglycemia
- Severe electrolyte abnormalities
- Can be life-threatening if untreated 3
Important Clinical Considerations
- Symptoms often develop gradually and may be nonspecific, leading to delayed diagnosis 4
- Adrenal crisis can be precipitated by stressors such as infection, trauma, surgery, or abrupt withdrawal of glucocorticoid therapy 1
- Up to 50% of patients with autoimmune Addison's disease may develop other autoimmune disorders, including thyroid disease, type 1 diabetes, and premature ovarian insufficiency 1
- Patients with adrenal insufficiency require lifelong hormone replacement therapy and education about stress dosing to prevent adrenal crisis 1
Diagnostic Pitfalls to Avoid
- Mistaking nonspecific symptoms for other conditions, leading to delayed diagnosis
- Failing to consider adrenal insufficiency in patients with unexplained fatigue, weight loss, and hypotension
- Not recognizing that hyperpigmentation is specific to primary adrenal insufficiency
- Overlooking adrenal insufficiency in patients on chronic glucocorticoid therapy who present with symptoms after dose reduction or discontinuation 2
- Failing to perform appropriate diagnostic testing (morning cortisol and ACTH levels, ACTH stimulation test) when adrenal insufficiency is suspected 1
Early recognition of these symptoms is crucial to prevent potentially life-threatening adrenal crisis and initiate appropriate hormone replacement therapy.