Huntington’s disease (HD), characterized by progressive dementia and movement disabilities, is dominantly inherited and begins before age 40. Premature aging like neuronal degeneration and lipofuscin accumulation occur in parts of the cerebral cortex, caudate nucleus and hypothalamus. Post mortem analysis of the basal ganglia indicates a variety of neurotransmitter abnormalities occur.
Eighteen patients with Huntington’s disease were studied by oral and L-dopa modified glucose tolerance tests (GTT) and intravenous arginine tolerance tests, performed under standardized metabolic conditions. The GTT was repeated in 14 patients after three days of L-dopa administered 0.5 g three times daily plus 0.5 g given 30 minutes prior to the repeat test. Seven patients had an initial diabetic type GTT. Mean peak plasma insulin level in the nondiabetic group occurred at 1/2 hour and was 60.2 ± 10.1 μU/ml, but in the diabetic group the peak insulin level occurred at 2 hours and was 155.9 ± 33.8 μU/ml. There was failure of suppression of growth hormone (GH) during the GTT, with a rise to abnormally high levels at 5 hours (18.6 ± 5.6 ng/ml). L-dopa abolished the glucose-induced GH suppression in control subjects and instead caused a sharp rise in GH. Patients with HD had elevated pretest GH levels (17.9 ± 2.3 ng/ml) with a prompt fall after L-dopa plus glucose. Arginine infusion resulted in elevated insulin levels in HD patients with impaired glucose tolerance, compared to the nondiabetic patients (91.9 ± 17.4 μU/ml vs 45.2 ± 5.7 μU/ml). Peak GH response to arginine occurred at one hour (28.3 ± 3.7 ng/ml) and was significantly higher in the series of patients with HD than in controls.
It is uncertain whether the neurotransmitter and endocrine abnormalities in HD are secondary to hypothalamic cell death or the initial cause of cellular dysfunction in the brain.
KeywordsGrowth Hormone Growth Hormone Response Peak Growth Hormone Lipofuscin Accumulation Growth Hormone Suppression
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