Are patients with Addison's disease at increased risk of complications?

From the Guidelines

Yes, patients with Addison's disease are at increased risk of complications, particularly adrenal crisis, which can be life-threatening if not promptly recognized and treated. The primary concern is adrenal crisis, a life-threatening emergency that can occur when the body is under stress and unable to produce sufficient cortisol 1. Common complications include severe hypotension, hypoglycemia, electrolyte imbalances (particularly hyponatremia and hyperkalemia), and metabolic acidosis. Patients may also experience chronic complications such as increased susceptibility to infections, poor wound healing, and psychological issues including depression and anxiety.

Some key points to consider in the management of patients with Addison's disease include:

• The frequency of acute adrenal crises among patients with primary adrenal insufficiency is 6–8 per 100 patient-years, and precipitating events are often vomiting and/or diarrhoea, infections, surgical procedures, injuries, myocardial infarction, severe allergic reactions, severe hypoglycaemia in diabetic patients and treatment failures in poorly educated or non-compliant patients 1.
• Patients require lifelong hormone replacement therapy, typically hydrocortisone (15-25 mg daily in divided doses) and fludrocortisone (0.05-0.2 mg daily), and must carry emergency medication (injectable hydrocortisone) and medical identification.
• During times of illness, injury, or surgery, steroid doses need to be increased to prevent adrenal crisis, following the "sick day rules" that typically involve doubling or tripling the usual glucocorticoid dose 1.
• The prevalence of adrenal insufficiency in adult and paediatric populations is significant, with approximately 1 in 8–10,000 children affected by primary adrenal insufficiency, and a larger population at risk of adrenal crisis due to prescribed glucocorticoid therapy 1.

Overall, patients with Addison's disease require careful management and monitoring to prevent complications and ensure optimal quality of life. The most recent guidelines recommend a comprehensive approach to the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency, including increased steroid doses and emergency medication 1.

From the FDA Drug Label

Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remission or exacerbations of the disease and stress (surgery, infection, trauma) The patients with Addison's disease are at increased risk of complications due to the disease itself and the need for continual monitoring for signs of exacerbation, especially during stress events like surgery, infection, or trauma 2.

• The disease requires substitution therapy with minimal risks of unwanted effects.
• Dosage adjustment is necessary in case of remission, exacerbation, or stress.

From the Research

Risk of Complications in Addison's Disease

Patients with Addison's disease are at an increased risk of complications due to the nature of their condition. The primary concern is the potential for an adrenal crisis, which is a life-threatening complication that can occur when the body's demand for hydrocortisone is not met 3.

Factors Contributing to Increased Risk

Several factors contribute to the increased risk of complications in patients with Addison's disease, including:

• Inadequate replacement therapy, which can lead to impaired health-related quality of life (HRQoL) and increased mortality 4
• Delayed diagnosis due to non-specific symptoms, particularly in the early stages of the disease 5, 6
• Increased prevalence of the disease, with recent data indicating a rise in cases 5
• Iatrogenic conditions, such as pharmacological side effects, which can contribute to the development of primary adrenal insufficiency (PAI) 5

Management and Prevention of Complications

Effective management and prevention of complications in Addison's disease rely on:

• Adequate patient education, which is a cornerstone in the prevention and management of adrenal crisis 5, 6
• Optimized glucocorticoid replacement therapy, with a focus on developing pharmacokinetically optimized preparations 5
• Continuous education of patients and healthcare professionals on the dangers of adrenal crisis and the importance of prompt treatment 6