Who is at risk for adrenal insufficiency?

Patients at Risk for Adrenal Insufficiency

Patients at risk for adrenal insufficiency include those with primary adrenal gland disorders, pituitary or hypothalamic disorders, and most commonly, individuals on long-term glucocorticoid therapy through any route of administration including oral, inhaled, topical, intranasal, and intra-articular. 1, 2

Types of Adrenal Insufficiency and At-Risk Populations

Primary Adrenal Insufficiency

Affects approximately 1 in 8-10,000 individuals and involves deficiency of all adrenocortical hormones (cortisol and aldosterone). At-risk populations include:

• Patients with autoimmune adrenalitis (Addison's disease) - most common cause in Western countries 2
• Individuals with congenital adrenal hyperplasia (occurs in 1 in 15,000 live births) 1
• Patients with adrenal gland infections (tuberculosis, fungal infections) 2
• Those on high doses of azole antifungal therapy 2
• Patients who have undergone adrenalectomy 2
• Individuals with adrenal hemorrhage or infarction 3
• Patients with infiltrative conditions affecting the adrenal glands 3

Secondary Adrenal Insufficiency

Affects approximately 1 in 10,000 children and involves cortisol deficiency with preserved aldosterone production. At-risk populations include:

• Patients with pituitary tumors or who have undergone pituitary surgery 2, 4
• Individuals with pituitary hemorrhage 2
• Those with inflammatory or infiltrative conditions of the pituitary (hypophysitis, sarcoidosis, hemochromatosis) 2
• Patients who have received pituitary radiation therapy 2
• Individuals on medications that suppress corticotropin production (e.g., opioids) 2
• Patients with congenital causes such as developmental disorders of the hypothalamus and pituitary 1
• Those with acquired causes such as brain tumors and their treatment 1

Tertiary (Glucocorticoid-Induced) Adrenal Insufficiency

Most common form of adrenal insufficiency, affecting seven in 1,000 people on long-term oral corticosteroid therapy. At-risk populations include:

• Patients on any form of exogenous glucocorticoid therapy (oral, inhaled, topical, intranasal, intra-articular) 1, 2
• Children with asthma, renal disease, inflammatory conditions (juvenile chronic arthritis, inflammatory bowel disease), and Duchenne's muscular dystrophy on steroid treatment 1
• Patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 2

Comorbidities Increasing Risk of Adrenal Crisis

Certain comorbidities increase vulnerability to adrenal crisis in patients with adrenal insufficiency:

• Asthma 1
• Diabetes 1
• Mineralocorticoid dependency 1
• Vasopressin dependency 1

Common Precipitating Factors for Adrenal Crisis

Patients with adrenal insufficiency are at risk of adrenal crisis when exposed to:

• Gastroenteritis or fever 1
• Surgical episodes 1
• Pregnancy 1
• Emotional distress 1
• Sepsis 5
• Physical stress 2
• Acute illness 2
• Medication errors or omissions during hospitalization 1

Special Considerations

• Inhaled corticosteroid therapy, even at commonly prescribed doses, can cause suppression of the adrenal response to ACTH in a dose-dependent manner 1
• Patients with comorbidities like asthma and diabetes are more vulnerable to adrenal crisis 1
• Medications that induce CYP3A4 and bulking agents like psyllium may interfere with glucocorticoid absorption, potentially triggering adrenal crisis 6
• Hypoglycemia is a significant risk in adrenal insufficiency, particularly in neonates but also in older children and adults 3

Clinical Implications

The mortality risk is significantly elevated in patients with adrenal insufficiency, with risk ratios of 2.19 for men and 2.86 for women 1. Adrenal crises requiring hospital treatment occur about 6-8 times per 100 patient years 1. Approximately 8.6% of patients with chronic adrenal insufficiency report having experienced an adrenal crisis during an inpatient stay 1.

All patients with adrenal insufficiency should be educated on recognizing early symptoms of adrenal crisis, wear medical alert identification, carry a steroid alert card, have an emergency hydrocortisone injection kit, and know when and how to adjust medication during illness or stress 6.