Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients

Non-motor symptoms associated with autonomic dysfunction have a strong impact on the prognosis and quality of life in patients with multiple system atrophy (MSA). Patients with MSA often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using the gastrointestinal domain of the scales for outcomes in Parkinson’s disease-autonomic (SCOPA-AUT). Age at the time of evaluation, sex distribution, and body mass index were matched across the three groups, and disease duration and levodopa equivalent daily doses were matched for the two patient groups. The SCOPA-AUT gastrointestinal score was significantly higher in the MSA group than in the other two groups (P = 0.001). The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0%) than in patients with other atypical parkinsonian disorders (mean: 13.7%, P = 0.001) and control subjects (mean: 13.9%, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = -0.5, P = 0.004). This phenomenon was not observed in patients with other atypical parkinsonian disorders (P = 0.6) and control subjects (P = 0.9). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA. Pharmacological interventions that have therapeutic value in relation to increasing plasma active ghrelin should be considered for gastrointestinal symptoms in patients with MSA.