Distinction of idiopathic Parkinsonʹs disease from multiple-system atrophy by stimulation of growth-hormone release with clonidine

Background Idiopathic Parkinsonʹs disease is a common neurodegenerative disease that is difficult to distinguish from other parkinsonian syndromes such as multiple-system atrophy (MSA). In MSA, autonomic dysfunction is common and is associated with either parkinsonian or cerebellar features, or both. Differentiation of idiopathic Parkinsonʹs disease from MSA is important because prognosis, complications, and response to therapy vary according to disorder. Our aim was to find out whether clonidine/growth hormone (GH) testing distinguishes idiopathic Parkinsonʹs disease from MSA. Methods Clonidine is a centrally active α2-adrenoceptor agonist that raises concentrations of GH in serum in healthy people and those with pure autonomic failure (with peripheral lesions), but not in those with MSA (with a central autonomic deficit). We investigated the effects of clonidine on 14 people with idiopathic Parkinsonʹs disease (without autonomic deficits), 31 people with MSA of the three different clinical forms (parkinsonian, cerebellar, and mixed), 19 people with pure autonomic failure, and 27 healthy participants. In nine people with parkinsonian MSA (MSA-P), the GH response to levodopa was also assessed. Findings Clonidine raised serum GH concentrations in patients with idiopathic Parkinsonʹs disease (median increase 8·98 [IQR 6·6–16·6] mU/L), normal participants (13·2 [7·0–18·6] mU/L), and patients with pure autonomic failure (12·5 [5·6–18·2] mU/L). In those with MSA who had central autonomic failure, GH concentrations were unchanged (MSA-P; 0·41 [−0·30 to 2·09] mU/L and cerebellar MSA [MSA-C] 1·67 [0–4·49] mU/L). The GH response to clonidine in idiopathic Parkinsonʹs disease was significantly different from that in MSA-P (p<0·0002). In MSA-P, the dopamine precursor levodopa raised GH concentrations (from mean 2·7 [SE 1·0] mU/L to mean 18·2 [6·0] mU/L, p<0·05) and GH-releasing hormone (GHRH) concentrations (from mean 20·6 [3·25] ng/L to mean 68·0 [10·6] ng/L, p<0·05), excluding dysfunction of pituitary somatotrophs or GHRH neurons as a cause for the absent GH response to clonidine in MSA. Interpretation The GH responses to clonidine clearly differentiated idiopathic Parkinsonʹs disease from MSA-C and MSA-P. Together with the levodopa studies they indicated a specific α2-adrenoceptor-hypothalamic deficit in MSA. The clonidine-GH test may provide further insight into central neurotransmitter and α2-adrenoceptor-hypothalamic abnormalities in MSA.