Symptoms of Addison's Disease
The primary symptoms of Addison's disease include fatigue, weakness, weight loss, hypotension, salt craving, hyperpigmentation of skin and mucous membranes, nausea, and electrolyte abnormalities such as hyponatremia and hyperkalemia. 1, 2
Common Clinical Manifestations
Constitutional Symptoms
- Fatigue and weakness (often severe and progressive)
- General malaise
- Anorexia
- Weight loss (can be significant)
- Dizziness, especially when standing (orthostatic hypotension)
Skin and Mucosal Changes
- Hyperpigmentation (darkening of the skin), particularly in:
- Sun-exposed areas
- Palmar creases
- Frictional surfaces
- Vermilion border of the lips
- Recent scars
- Genital skin
- Oral mucosa
Gastrointestinal Symptoms
- Nausea
- Poor appetite
- Diarrhea
- Salt craving
Cardiovascular Manifestations
- Hypotension (often orthostatic)
- Syncope or near-syncope
Metabolic Abnormalities
- Hyponatremia (low sodium)
- Hyperkalemia (high potassium or potassium in upper normal range)
- Hypoglycemia (particularly during fasting or stress)
Symptom Progression and Presentation
The onset of symptoms in Addison's disease is typically insidious, developing gradually over months to years 3, 4. This slow progression often leads to delayed diagnosis, as many symptoms are non-specific and may be attributed to other conditions 2.
Symptoms may worsen during periods of stress, illness, or injury when the body requires increased cortisol that the adrenal glands cannot provide 1.
Warning Signs of Adrenal Crisis
Adrenal crisis is a life-threatening emergency that may develop in patients with untreated or undertreated Addison's disease, particularly during stress or illness 1:
- Severe hypotension
- Severe weakness
- Confusion or altered mental status
- Fever
- Severe abdominal pain
- Vomiting and diarrhea
- Loss of consciousness
Diagnostic Considerations
The combination of hyperpigmentation with fatigue, weight loss, and hypotension should raise strong suspicion for Addison's disease 2, 5. Laboratory findings typically show:
- Low morning cortisol levels
- Elevated ACTH levels (distinguishing primary from secondary adrenal insufficiency)
- Electrolyte abnormalities (hyponatremia, hyperkalemia)
- Elevated plasma renin activity
Clinical Pitfalls to Avoid
- Many symptoms of Addison's disease are non-specific and may be attributed to other conditions, leading to delayed diagnosis 4, 6
- Hyperpigmentation is a distinctive feature that should prompt consideration of Addison's disease 5
- Symptoms may be masked or exacerbated by other medications or conditions
- Adrenal crisis can develop rapidly during stress and is life-threatening if not promptly treated 1
Early recognition of the constellation of symptoms is critical, as untreated Addison's disease can progress to life-threatening adrenal crisis, while proper treatment allows patients to resume normal daily activities with good quality of life 2.