Brain Atrophy and Cognitive Deficits in Cushing's Disease

Abstract and Introduction

Abstract

Cushing's disease is associated with brain atrophy and cognitive deficits. Excess glucocorticoids cause retraction and simplification of dendrites in the hippocampus, and this morphological change probably accounts for the hippocampal volume loss. Mechanisms by which glucocorticoids affect the brain include decreased neurogenesis and synthesis of neurotrophic factors, impaired glucose utilization, and increased actions of excitatory amino acids. In this review, the timing, pathology, and pathophysiology of the brain atrophy in Cushing's disease are discussed. The correlation of atrophy with cognitive deficits and its reversibility is also reviewed.

Introduction

Cushing's disease results from sustained pathological hypercortisolism secondary to excessive adrenocorticotropin hormone secretion by tumors of the pituitary gland. Clinical features of Cushing's disease such as abnormal fat distribution, wide violaceous striae, hirsutism, impaired glucose tolerance, and osteoporosis are often discussed and investigated. The experienced clinician, however, is very aware of the rarely discussed, but often disabling, cognitive deficits and emotional symptoms that accompany Cushing's disease. In this review, we discuss the neurobiological basis of these impairments. We previously documented a striking radiographic feature of pathological hypercortisolism, namely the marked cortical and subcortical brain atrophy seen in patients with Cushing's disease (Fig. 1).^[19] Brain atrophy, especially in the hippocampus, has been well documented in both adult and pediatric patients treated with exogenous glucocorticoid therapy.^{[1,2,5,6,16,21]} In this review, the timing, pathology, and pathophysiology of glucocorticoid-induced brain atrophy are discussed. In addition, the limited information specific to hippocampal atrophy, cognitive impairments, and mood disorders in Cushing's disease is presented.