title: Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications.
abstract: Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.
authors.affiliation: Department of Pediatric Neurology, Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK ; Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Italy.
authors.forename: Vincenzo
authors.identifier: 0000-0001-6290-2032
authors.initials: V
authors.lastname: Salpietro
authors.affiliation: National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy ; Institute of Neurological Sciences, National Research Council, Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Polizzi
authors.affiliation: Infantile Neuropsychiatry Unit, Department of Pediatrics, University of Messina, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Rosa
authors.affiliation: Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Italy.
authors.forename: Anna Claudia
authors.initials: AC
authors.lastname: Romeo
authors.affiliation: Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Dipasquale
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
authors.forename: Paolo
authors.identifier: 0000-0002-4030-918X
authors.initials: P
authors.lastname: Morabito
authors.affiliation: Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chirico
authors.affiliation: Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.affiliation: Chair of Pediatrics, Department of Educational Sciences, University of Catania, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri