Adrenal Insufficiency Among Children Treated with Hormonal Therapy for Infantile Spasms

Background: Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given, and long treatment duration expose patients to the risk of adrenal insufficiency (AI). There is presently limited data on the occurrence of adrenal suppression following hormonal therapy in this population. No evidence recommends any test or hydrocortisone replacement following the hormone treatment even if the consequences of that adrenal suppression can be severe. A case of an adrenal crisis at our center motivated us to look further into the risk of developing AI in such patients. This study aims to quantify the incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone (ACTH).

Methods: A retrospective chart review of patients treated for infantile spasms was performed between January 2009 and March 2020 in one pediatric specialized hospital. Variables collected included patient and treatment characteristics, risk factors of AI, hydrocortisone replacement therapy use, adrenal function testing and signs of AI. Analysis included descriptive statistics such as incidence and bivariate analysis. The Institutional Review Board of the hospital approved the study (MP-20-2020-5148).

Results: Thirty-one patients were included and received a total of 33 separated courses of treatment (17 corticosteroids [prednisone/prednisolone], 12 ACTH and 4 combined). Adrenal function was assessed in 32/33 (97%) children either by tests or by the presence of an adrenal crisis. Hydrocortisone replacement therapy was received by 32/33 (97%) children. AI occurred in 25/33 (76% [95CI 58-89]) children. There was no predictive factor of AI after hormonal treatment. No drug regimen was found to be safe. The two patients (6%) with an acute adrenal crisis presented to the emergency room the days following weaning off hormonal treatment. They were the youngest children of the cohort with an age of 1,6 and 2,7 months at the initiation of treatment. All other patients were aged 4 months and older. They both received prednisolone.

Conclusion: Adrenal insufficiency is frequent and can lead to an adrenal crisis in this population. As such, routine laboratory assessment of adrenal function should be done in all patients, and we recommend that a hydrocortisone replacement therapy should be given until normal testing results are obtained.