Most Serious Complications of Congenital Adrenal Hyperplasia
The most serious complication of congenital adrenal hyperplasia is acute adrenal crisis, which carries a mortality rate of 0.5 per 100 patient-years and occurs at a frequency of 6-8 events per 100 patient-years. 1, 2
Life-Threatening Adrenal Crisis
Adrenal crisis represents the primary cause of mortality in CAH patients and requires immediate recognition and treatment. The crisis manifests as:
- Electrolyte derangements: Hyponatremia and hyperkalemia due to mineralocorticoid deficiency, leading to inability to regulate electrolyte balance 3
- Cardiovascular collapse: Shock and severe hypotension from volume depletion and electrolyte imbalance 3, 2
- Neurological deterioration: Impaired cognitive function, confusion, loss of consciousness, and coma 3
In neonates with salt-wasting CAH (75% of classic cases), failure to diagnose can result in serious harm as these patients cannot regulate their electrolyte levels and may present with shock, hyponatremia and hyperkalemia. 3 This is particularly critical because infants under 6 months old have significantly higher rates of emergency department visits compared to older children with CAH. 4
Precipitating Factors for Crisis
The most common triggers include:
- Gastrointestinal illness: Vomiting and/or diarrhea are the most frequent precipitating events 3
- Infections: Any febrile illness can trigger crisis 3, 2
- Surgical stress: Procedures without adequate stress-dose coverage 3, 2
- Treatment failure: Poor compliance or inadequate patient education—only 50% of illness-related emergency visits in young CAH children are preceded by appropriate stress dosing 4
Critical Diagnostic Pitfall in Newborns
A phenotypic male newborn with bilateral nonpalpable testes must be immediately evaluated for CAH, as a 46 XX individual with severe CAH can be mistaken for a boy with bilateral cryptorchidism. 3 Failure to recognize this presentation delays diagnosis and increases risk of life-threatening salt-wasting crisis.
Long-Term Morbidity Complications
Beyond acute crisis, CAH patients face significant chronic complications:
Cardiovascular and Metabolic
- Increased mortality risk: 2.19-fold higher in men and 2.86-fold higher in women with adrenal insufficiency 1
- Cardiometabolic disease: Insulin resistance, cardiovascular disease, metabolic syndrome, and hypertension from chronic glucocorticoid therapy 5, 6
Growth and Development
- Growth abnormalities: Rapid early childhood growth with advanced skeletal age, but compromised final adult height if androgen excess is not controlled 6, 7
- Premature adrenarche: Early development of pubic hair and acne from excess androgens 5, 6
Reproductive Complications
- Impaired fertility: Both males and females experience reproductive dysfunction 6, 8
- Testicular adrenal rest tumors: Occur in males with poorly controlled disease 5
- Menstrual irregularities and hirsutism: Common in females with inadequate androgen suppression 6, 7
Skeletal Health
- Osteoporosis: From chronic glucocorticoid overtreatment; bone mineral density should be monitored every 3-5 years 2, 6
Prevention of Serious Complications
The key to preventing mortality and serious morbidity is immediate treatment when crisis is suspected—never delay administration of 100 mg intravenous hydrocortisone and rapid infusion of 0.9% saline (1 L over one hour). 3, 2 Blood samples for cortisol and ACTH should be obtained before treatment if feasible, but therapy must not be delayed. 3, 2
All CAH patients must:
- Wear medical alert identification and carry steroid emergency cards 2
- Have ready-to-use hydrocortisone injection kits with clear self-administration instructions 2
- Receive comprehensive education on stress dosing: double or triple oral hydrocortisone during febrile illness, vomiting, or diarrhea 2
- Understand that electrolyte abnormalities and administration of parenteral hydrocortisone in the emergency department significantly predict hospital admission 4