Signs of Addison's Disease
Addison's disease presents with a characteristic constellation of chronic symptoms including hyperpigmentation, fatigue, weight loss, and hypotension, along with laboratory findings of hyponatremia (in 90% of cases), hyperkalaemia (in 50% of cases), low cortisol, and elevated ACTH. 1
Chronic Clinical Manifestations
Cutaneous Signs
- Hyperpigmentation is the hallmark cutaneous finding, appearing as darkening of the skin especially in sun-exposed areas 2
- Hyperpigmentation of palmar creases, frictional surfaces (elbows, knees), vermilion border of lips, recent scars, genital skin, and oral mucosa 2
- The pigmentation often has an uneven distribution pattern 3
Constitutional Symptoms
- Persistent fatigue and lethargy are nearly universal presenting complaints 4, 2
- Muscle weakness (myasthenia) 4
- Unintentional weight loss 4, 2
- Poor appetite and anorexia 2, 5
- Salt craving is a specific symptom reflecting mineralocorticoid deficiency 1
Gastrointestinal Manifestations
- Nausea occurs in 20-62% of patients 6
- Vomiting 5
- Diarrhea 2, 5
- Morning nausea and lack of appetite are particularly common 6
Cardiovascular Signs
Musculoskeletal Symptoms
Neuropsychiatric Manifestations
Laboratory Findings
Electrolyte Abnormalities
- Hyponatremia is present in 90% of newly diagnosed cases 6, 1
- Hyperkalaemia occurs in approximately 50% of cases 1
- Important caveat: The absence of hyperkalemia cannot rule out Addison's disease 6
- Mild to moderate hypercalcemia occurs in 10-20% of patients at presentation 6
Hormonal Findings
- Low serum cortisol (<250 nmol/L or <9 μg/dL) 6, 1
- Elevated plasma ACTH levels 1, 2
- Low DHEAS, androstenedione, and testosterone levels indicating androgen deficiency 7
Other Laboratory Abnormalities
- Hypoglycemia (particularly in children during acute crisis) 3
- Increased creatinine due to prerenal renal failure (in acute crisis) 3
Acute Adrenal Crisis Presentation
When Addison's disease decompensates into acute adrenal crisis, the presentation becomes more dramatic and life-threatening:
- Malaise and severe fatigue 3
- Nausea and vomiting 3
- Abdominal pain, sometimes with peritoneal irritation 3
- Dehydration leading to hypotension and shock 3
- Fever 2
- Loss of consciousness and coma 3
- Seizures (unusual presentation) 5
Clinical Pitfalls to Recognize
The insidious nature of symptom development over months to years often leads to delayed diagnosis 1, 8. Symptoms are frequently non-specific in early stages, and the disease is often not considered initially 8.
Do not rely solely on electrolyte abnormalities for diagnosis—some patients may have normal electrolytes or only mild abnormalities at presentation 6. Between 10-20% of patients have mild or moderate hypercalcemia rather than the expected hyponatremia 6.
Hyperpigmentation with uneven distribution combined with "flu-like" symptoms that are intermittent but repetitive should raise immediate suspicion for Addison's disease 9.