Symptoms of Addison's Disease
Addison's disease typically presents with insidious, nonspecific symptoms that develop over months to years, including persistent fatigue, weakness, weight loss, hypotension, and the characteristic finding of hyperpigmentation of the skin and mucous membranes. 1, 2
Cardinal Clinical Features
Nonspecific Constitutional Symptoms
- Persistent fatigue and malaise are among the most common presenting complaints, often severe enough to interfere with daily activities 3, 4, 5
- Unintentional weight loss occurs frequently, with patients potentially losing significant weight (e.g., 7 kg in four weeks) 3, 6
- Anorexia and nausea are common gastrointestinal manifestations 4
- Myasthenia (muscle weakness) contributes to the overall sense of debilitation 3
- Salt craving is a specific symptom related to aldosterone deficiency 2
Characteristic Physical Findings
- Hyperpigmentation is the most diagnostically specific sign, affecting skin (especially areas subjected to friction) and mucous membranes, caused by elevated ACTH levels stimulating melanocytes 1, 3, 6
- Hypotension results from aldosterone deficiency and volume depletion 1, 3, 6
Laboratory Abnormalities (Often the First Clue)
- Hyponatremia is present in 90% of newly diagnosed cases, though sodium levels may be only marginally reduced 1, 2
- Hyperkalaemia occurs in approximately 50% of patients at diagnosis (not the "classical" combination with hyponatremia in all cases) 1, 2
- Hypoglycemia can occur, particularly in children, and may even present as hypoglycemic seizures 1
- Mild hypercalcemia is found in 10-20% of patients at presentation 1
- Anemia, mild eosinophilia, lymphocytosis, and increased liver transaminases may also be present 1
Important Clinical Caveats
Diagnostic Pitfalls
- Symptoms do not occur until most of the adrenal gland has been destroyed, leading to delayed diagnosis 4
- The insidious onset and nonspecific nature of symptoms frequently results in significant diagnostic delays 5, 6
- In patients with severe vomiting, hypokalaemia and alkalosis may be present instead of the expected hyperkalaemia, confounding the clinical picture 1
- Serum cortisol may be within the normal range in some patients, but is inappropriately low for the disease state (e.g., in sepsis) 1
Neuropsychiatric Manifestations
- Depression and psychosis can occur as neuropsychiatric manifestations of Addison's disease 3
- Persistent lack of libido and low energy may persist despite optimized glucocorticoid and mineralocorticoid replacement, reflecting androgen deficiency 7
Associated Findings
- TSH levels may be elevated (typically 4-10 IU/L) due to lack of cortisol's inhibitory effect on TSH production 1
- Reduced stress tolerance and weariness are common complaints even on standard replacement therapy 8
When to Suspect Addison's Disease
The diagnosis should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, with clinical suspicion heightened by the presence of hyperpigmentation, hyponatremia, hyperkalaemia, acidosis, or hypoglycemia. 1, 2