From the Guidelines
Addison's disease presents with a constellation of symptoms resulting from insufficient cortisol and aldosterone production by the adrenal glands, including extreme fatigue, weight loss, decreased appetite, low blood pressure, salt craving, hyperpigmentation, muscle and joint pain, nausea, vomiting, diarrhea, irritability, depression, and low blood sugar, as noted in the consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency 1, 2, 3. The disease often develops slowly, with symptoms appearing gradually over months, making early diagnosis challenging. Some key signs and symptoms to look out for include:
- Extreme fatigue
- Weight loss
- Decreased appetite
- Low blood pressure (especially orthostatic hypotension)
- Salt craving
- Hyperpigmentation (darkening of skin, particularly in skin folds, pressure points, and mucous membranes)
- Muscle and joint pain
- Nausea, vomiting, diarrhea
- Irritability, depression
- Low blood sugar Women may experience decreased axillary and pubic hair and reduced libido. Acute adrenal crisis, a life-threatening complication, can occur during times of stress and presents with severe abdominal pain, vomiting, diarrhea, dehydration, low blood pressure, and loss of consciousness, as outlined in the treatment guidelines for acute adrenal insufficiency 1. Laboratory findings typically show low sodium, high potassium, low cortisol, and elevated ACTH levels, which are diagnostic of primary adrenal insufficiency, as stated in the consensus statement 2. These symptoms occur because cortisol regulates stress response, metabolism, and immune function, while aldosterone maintains sodium and potassium balance, and without these hormones, the body cannot properly respond to stress or maintain electrolyte balance, leading to the characteristic symptoms of Addison's disease. Regular monitoring and follow-up are essential to manage the condition effectively, including annual reviews to assess health and well-being, measurement of weight, blood pressure, and serum electrolytes, as recommended in the follow-up guidelines 2.
From the Research
Signs and Symptoms of Addison's Disease
The signs and symptoms of Addison's disease are non-specific and can be overlooked or misleading, often leading to a delayed diagnosis 4, 5. The main symptoms include:
- Fatigue and general malaise
- Electrolyte imbalance disorders, such as hyponatremia
- Weight loss
- Anorexia
- Diarrhea
- Joint and back pain
- Orthostatic hypotension
- Fever
- Hypoglycemia
Cutaneous Manifestations
Addison's disease can also present with cutaneous manifestations, including:
- Hyperpigmentation of the skin, especially in sun-exposed areas
- Darkening of the skin
- Hyperpigmentation of the palmar creases, frictional surfaces, vermilion border, recent scars, genital skin, and oral mucosa 6
Diagnostic Features
Specific diagnostic features that should raise clinical suspicion of Addison's disease include:
- Hyperpigmentation
- Severe hypotension
- Electrolyte imbalance disorders, such as hyponatremia
- Elevated plasma levels of adrenocorticotropin and renin 7, 6
Laboratory Tests
Laboratory tests that can help establish a diagnosis of Addison's disease include:
- Measurement of basal plasma cortisol
- Synthetic adrenocorticotropin 1-24 test
- Elevated plasma levels of adrenocorticotropin and renin 6