What are the symptoms of Addison's disease?

Symptoms of Addison's Disease

Addison's disease presents with insidious, nonspecific symptoms that develop over months to years, including profound fatigue, weight loss, salt craving, hyperpigmentation of the skin (especially sun-exposed areas and friction points), gastrointestinal complaints, and orthostatic hypotension. 1

Primary Clinical Manifestations

Constitutional Symptoms

• Profound fatigue and malaise are the most common presenting complaints, often described as persistent weariness and reduced stress tolerance 1, 2
• Unintentional weight loss occurs due to anorexia and metabolic derangements 2, 3
• Muscle weakness (myasthenia) affecting daily activities 2

Gastrointestinal Symptoms

• Nausea occurs in 20-62% of patients, frequently accompanied by vomiting 4
• Poor appetite and anorexia are characteristic features 5, 3
• Diarrhea may be present 3
• Morning nausea and lack of appetite are particularly common and may indicate glucocorticoid under-replacement 4

Cardiovascular Manifestations

• Orthostatic hypotension (low blood pressure when standing) is a hallmark feature 3
• Persistent hypotension that may be refractory to standard treatments 4

Distinctive Dermatologic Features

• Hyperpigmentation is pathognomonic, appearing as darkening of the skin in:
  • Sun-exposed areas 3
  • Palmar creases 3
  • Frictional surfaces (elbows, knees) 3
  • Vermilion border of the lips 3
  • Recent scars 3
  • Genital skin 3
  • Oral mucosa 3
• This hyperpigmentation results from elevated ACTH levels stimulating melanocytes 1

Metabolic and Electrolyte Disturbances

• Salt craving is a specific clinical clue for primary adrenal insufficiency 1, 4
• Hypoglycemia may occur, particularly during acute crisis 3

Neuropsychiatric Manifestations

• Depression can be a presenting feature 2
• Psychosis may occur in some cases 2

Musculoskeletal Symptoms

• Joint pain and back pain are reported 3

Laboratory Correlates of Symptoms

While not symptoms per se, these laboratory findings accompany the clinical picture:

• Hyponatremia is present in 90% of newly diagnosed cases 1
• Hyperkalemia occurs in approximately 50% of cases 1
• Low serum cortisol with elevated ACTH confirms the diagnosis 1

Critical Pitfall to Recognize

The symptoms are often nonspecific and insidious, typically not appearing until 90% of the adrenal cortex has been destroyed, leading to delayed diagnosis. 5, 6 This means patients may have vague complaints for months before the diagnosis is considered. The combination of fatigue, weight loss, hyperpigmentation, and salt craving should immediately raise suspicion for Addison's disease. 1, 3

Acute Adrenal Crisis Presentation

When Addison's disease decompensates into acute adrenal crisis, symptoms escalate dramatically:

• Unexplained collapse 4
• Severe hypotension requiring vasopressors 4
• Fever 3
• Severe vomiting or diarrhea 4
• Profound weakness 4

This is a life-threatening emergency requiring immediate treatment with IV hydrocortisone 100 mg and rapid saline infusion—treatment should never be delayed for diagnostic procedures. 1, 4

Associated Autoimmune Conditions

Approximately half of patients with autoimmune Addison's disease have other co-existing autoimmune diseases, which may present with their own symptom complexes:

• Primary hypothyroidism (part of autoimmune polyendocrine syndrome type-2) 1
• Hypoparathyroidism (part of autoimmune polyendocrine syndrome type-1) 1
• Chronic mucocutaneous candidiasis (part of APS-1) 1

Symptoms of Androgen Deficiency

In addition to cortisol and aldosterone deficiency, patients experience adrenal androgen loss:

• Persistent lack of libido despite optimized glucocorticoid and mineralocorticoid replacement 7
• Low energy levels that persist even with adequate hormone replacement 7
• This is particularly clinically significant in women, as the adrenal glands are their primary source of androgens 7