What are the clinical features of Addison's disease?

From the Guidelines

Addison's disease presents with a constellation of symptoms resulting from insufficient adrenal hormone production, including chronic fatigue, muscle weakness, weight loss, and hyperpigmentation of the skin, as well as gastrointestinal symptoms, mood changes, and laboratory findings such as low serum cortisol and electrolyte imbalances. The clinical features of Addison's disease are a result of the lack of glucocorticoid and mineralocorticoid hormones produced in the adrenal cortex, irrespective of the etiology of the condition 1. Patients with primary adrenal insufficiency (PAI), also known as Addison's disease, often have co-existing autoimmune diseases, such as autoimmune thyroid disease, type-1 diabetes mellitus, and premature ovarian insufficiency (POI) 1.

Common Clinical Features

• Chronic fatigue and muscle weakness
• Weight loss and decreased appetite
• Salt craving and hyperpigmentation of the skin (particularly in skin folds, scars, and mucous membranes)
• Postural hypotension, causing dizziness when standing up
• Gastrointestinal symptoms like nausea, vomiting, abdominal pain, and diarrhea
• Mood changes including irritability, depression, and anxiety

Laboratory Findings

• Low serum cortisol
• Elevated ACTH
• Hyponatremia (low sodium)
• Hyperkalemia (high potassium)
• Sometimes hypoglycemia These symptoms develop gradually as the adrenal cortex deteriorates, with clinical manifestations usually not appearing until at least 90% of the adrenal tissue has been destroyed 1. An Addisonian crisis, characterized by severe hypotension, shock, and altered mental status, can occur during times of stress when the body cannot increase cortisol production appropriately, representing a medical emergency requiring immediate treatment with intravenous hydrocortisone, fluids, and glucose.

From the Research

Clinical Features of Addison's Disease

The clinical features of Addison's disease, also known as primary adrenal insufficiency, are characterized by:

• Deficiency of glucocorticoids and mineralocorticoids due to failure of the adrenal cortex 2
• Chronic glucocorticoid- and/or mineralocorticoid deficiency, which may result in an adrenal crisis with potentially life-threatening consequences 2
• Non-specific symptoms, especially in the early stages, making it frequently not considered, resulting in a delayed diagnosis 2, 3

Symptoms of Addison's Disease

Common symptoms of Addison's disease include:

• Malaise 4
• Anorexia 4
• Diarrhea 4
• Weight loss 4
• Joint and back pain 4
• Fatigue, weariness, and reduced stress tolerance 5
• Orthostatic hypotension, fever, and hypoglycemia in acute adrenal crisis 4

Cutaneous Manifestations

The cutaneous manifestations of Addison's disease include:

• Darkening of the skin, especially in sun-exposed areas 4
• Hyperpigmentation of the palmar creases, frictional surfaces, vermilion border, recent scars, genital skin, and oral mucosa 4

Diagnostic Aspects

Diagnosis of Addison's disease involves:

• Measurement of basal plasma cortisol, although it is an insensitive screening test 4
• Synthetic adrenocorticotropin 1-24 as a dynamic test 4
• Elevated plasma levels of adrenocorticotropin and renin to confirm the diagnosis 4