Assessment of Persistent Cognitive Impairment After Cure of Cushing's Disease

Cognitive Sequels of Cushing Syndrome

Cushing's disease is a state of chronic endogenous glucocorticoid excess. Cushing's disease is responsible for increased morbidity and mortality. Recent studies have pinpointed the frequency of somatic sequelas and persistent alteration in quality of life despite the cure of the disease. More specifically, a few studies have described persistent psychopathology, maladaptive personality and cognitive impairments in patients with a history of Cushing's disease. Among these, hippocampal memory deficits have been found in the majority of studies, a finding that is consistent with the alterations described in hippocampal neurons during chronic exposure to glucocorticoids. However, the tools currently available to assess hippocampal-dependent memory are multiple, sometimes difficult to perform by clinicians and to analyze or may lack of diagnostic sensitivity. The investigators have recently developed an original tool, the virtual radial task in 3D, which has shown to be reliable to detect subtle alterations in hippocampal-dependent memory in several human diseases. The primary aim of the study is the evaluation of persistent cognitive impairments (hippocampal memory) in patients cured of Cushing's disease for at least one year using the virtual radial task in 3D and to compare it with that obtained with classical cognitive tests.

Inclusion Criteria:

Patients :

• history of Cushing's Disease
• aged : 18 - 60 years
• Biological remission of Cushing's disease for at least one year
• Affiliation to Social Security
• Informed consent signed by patient and investigator (at the latest the inclusion's day, before study's exams)

For controls :

• People aged 18 to 60 years matched to patients for age, sex and educational level
• Affiliation to Social Security
• Informed consent signed by patient and investigator (at the latest the inclusion's day, before study's exams)

Exclusion Criteria:

For patients :

• Persistent hypercortisolism (even mild)
• Current treatment of hypercortisolism with drugs
• Obesity (BMI >30 kg/m²)
• Alcohol or drug addiction present or past
• Growth hormone deficit
• Diabetes mellitus with hemoglobin A1c > 7.5% and/or fasting blood glucose > 1.4 g/L
• History of pituitary radiotherapy
• History of cerebrovascular or neuro-cerebral disease
• untreated dysthyroidism
• Current psychotropic drug treatment
• Pregnancy
• Use of glucocorticoids in the last 3 months before study (aside hydrocortisone replacement therapy)
• Excessive hydrocortisone replacement therapy (unadjusted to weight and/or with evening administration)

For controls :

• Obesity (BMI >30 kg/m²)
• Alcohol or drug addiction present or past
• Current psychotropic drug treatment
• History of cerebrovascular or neuro-cerebral disease
• Current pregnancy
• Chronical use of corticoid (> 1 month), current or past
• Use of glucocorticoids in the last 3 months before study (aside hydrocortisone replacement therapy)
• Diabetes mellitus with hemoglobin A1c > 7.5% and/or fasting blood glucose > 1.4 g/L
• Obesity (BMI >30 kg/m²)
• untreated dysthyroidism