Adrenal Disorders
Amy Wisniewski, PhD
Research Professor
Oklahom State University, United States
Glucocorticoids (GC) administered at supraphysiological doses can lead to a spectrum of psychiatric and cognitive symptoms, including anxiety, insomnia, behavioral disturbances, severe mood and psychotic disorders, delirium, and dementia. The severity of these issues correlates with the GC dosage given. Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a rare genetic condition that results in impaired cortisol synthesis and excess adrenal androgen production, often requiring lifelong supraphysiological GC treatment to manage the adrenal androgen excess. This literature review investigates the impact of supraphysiological GC therapy on psychiatric disorders and cognition in CAH, contributing to a better understanding of the neuropsychological consequences of chronic supraphysiological GC exposure.
Methods:
A comprehensive review of available literature between 1996-2023 was conducted, focusing on the use of supraphysiological doses of GC; defined as > 25mg/day of hydrocortisone (HC) or HC-dose equivalents and their effect on psychiatric disorders and cognition in patients with CAH. The search yielded a total of six relevant studies that included patients with CAH up to 65 years of age.
Results:
There is evidence for psychiatric disorders and impaired cognition in patients with CAH. The most consistent psychiatric disorders included mood and psychotic disorders. Suicidality and substance abuse were the second most common behaviors with discordant data regarding their correlation to supraphysiological GC use. Brain morphology in patients with CAH was profoundly altered by high doses of GC suggesting an increased risk of cognitive impairment with supraphysiological doses of GCs in these patients. The available published literature is limited and flawed by repetitive subgroup analyses, methodological issues, and the absence of controlling for confounding factors, such as disease-related psychiatric and cognitive disorders.
Discussion/Conclusion:
There is a spectrum of psychiatric disorders and cognitive impairment associated with administration of supraphysiological doses of GCs in patients with CAH. The gaps identified here emphasize the need for further research to better understand the mechanisms and risk factors involved. Multiple factors, including prolonged exposure to adrenal androgen excess and GC-induced deterioration of brain regions, may determine the cognitive impairment in patients with CAH. Increased awareness among healthcare providers is necessary to monitor patients who are receiving supraphysiological GC doses for signs of psychiatric and cognitive symptoms.