Longitudinal Assessment of Illnesses, Stress Dosing, and Illness Sequelae in Patients With Congenital Adrenal Hyperplasia

Context: Patients with congenital adrenal hyperplasia (CAH) are at risk for life-threatening adrenal crises. Management of illness episodes aims to prevent adrenal crises.

Objective: We evaluated rates of illnesses and associated factors in patients with CAH followed prospectively and receiving repeated glucocorticoid stress dosing education.

Methods: Longitudinal analysis of 156 patients with CAH followed at the National Institutes of Health Clinical Center over 23 years was performed. The rates of illnesses and stress-dose days, emergency room (ER) visits, hospitalizations, and adrenal crises were analyzed in relation to phenotype, age, sex, treatment, and hormonal evaluations.

Results: A total of 2298 visits were evaluated. Patients were followed for 9.3 ± 6.0 years. During childhood, there were more illness episodes and stress dosing than adulthood (P < 0.001); however, more ER visits and hospitalizations occurred during adulthood (P ≤ 0.03). The most robust predictors of stress dosing were young age, low hydrocortisone and high fludrocortisone dose during childhood, and female sex during adulthood. Gastrointestinal and upper respiratory tract infections (URIs) were the two most common precipitating events for adrenal crises and hospitalizations across all ages. Adrenal crisis with probable hypoglycemia occurred in 11 pediatric patients (ages 1.1 to 11.3 years). Undetectable epinephrine was associated with ER visits during childhood (P = 0.03) and illness episodes during adulthood (P = 0.03).

Conclusions: Repeated stress-related glucocorticoid dosing teaching is essential, but revised age-appropriate guidelines for the management of infectious illnesses are needed for patients with adrenal insufficiency that aim to reduce adrenal crises and prevent hypoglycemia, particularly in children.