Adrenal function during long-term ACTH therapy for patients with developmental and epileptic encephalopathy

Epilepsia Open. 2022 Mar;7(1):194-200. doi: 10.1002/epi4.12566. Epub 2021 Dec 14.

Abstract

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin-releasing hormone (CRH) stimulation test during LT-ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life-threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT-ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT-ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely.

Keywords: ACTH therapy; adrenal insufficiency; developmental and epileptic encephalopathy; long-term treatment.

MeSH terms

  • Adrenal Insufficiency* / chemically induced
  • Adrenal Insufficiency* / drug therapy
  • Adrenocorticotropic Hormone / therapeutic use
  • Brain Diseases*
  • Child
  • Corticotropin-Releasing Hormone
  • Humans
  • Hydrocortisone / therapeutic use

Substances

  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Hydrocortisone