The Impact of Overactive Adrenal Gland Disorders on Pediatric Brain Development

Overactive adrenal gland disorders can have significant consequences for pediatric patients, particularly when it comes to brain development and function. The assumption that children respond similarly to adults in terms of disease pathophysiology, medication efficacy, and adverse reactions is often incorrect. Further research is needed to fully understand the long-term effects of high doses of prolonged corticosteroid administration on childhood development.

Physicians must be aware of potential neurological manifestations in children with adrenal dysfunction to ensure timely diagnosis and treatment. Animal experiments and clinical studies have shown that the developing central nervous system (CNS) is particularly vulnerable to alterations induced by adrenal disorders or supraphysiological doses of corticosteroids.

The development of the CNS through childhood is tightly regulated by various factors, including intrinsic, paracrine, endocrine, and external modulators. Perturbations in any of these factors can result in consequences that affect the structure and function of the pediatric brain. Arterial hypertension caused by adrenal disorders has been associated with various neurological manifestations.

Idiopathic intracranial hypertension (IIH), a disorder characterized by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism. This reflects the potential involvement of the adrenal-brain axis in regulating CSF pressure homeostasis.

Exposure to excessive replacement of exogenous glucocorticoids in the pediatric age group has been linked to neurological and magnetic resonance imaging (MRI) abnormalities, including delayed myelination and brain atrophy. Childhood Cushing syndrome can also be associated with long-lasting cognitive deficits and abnormal behavior, even after resolution of hypercortisolism.

In this article, we will focus on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related pediatric nervous system involvement. We will discuss various neurological and psychiatric manifestations recorded in children with adrenal disorders, highlighting the importance of early diagnosis and treatment to minimize long-term consequences.