Growth hormone and ghrelin secretion are associated with clinical severity in Huntington's disease.
OBJECTIVE
Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder caused by an increased CAG repeat size in the huntingtin gene. Apart from neurological impairment, the disease is also accompanied by progressive weight loss, abnormalities in glucose homeostasis and a higher prevalence of diabetes mellitus, which may partly be caused by disturbed growth hormone (GH) and ghrelin secretion. Therefore, we aimed to perform a detailed analysis of GH and ghrelin secretion in HD patients in relation to clinical signs and symptoms.


METHODS
In nine early-stage, medication-free HD patients and nine age-, gender- and body mass index-matched controls, we measured serum GH levels every 10 min for 24 h and assessed ghrelin response to food intake. Multi-parameter auto-deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile, and total GH secretion rates as well as the regularity of GH secretion.


RESULTS
We found no significant differences in GH and ghrelin secretion characteristics between HD patients and controls (total GH secretion: 137 +/- 36 vs. 181 +/- 43 mU/l/24 h, respectively; P = 0.439). However, in HD patients, both GH secretion and its irregularity as well as the degree of postprandial ghrelin suppression significantly increased with worsening motor and functional impairment (all P < 0.05). Moreover, postprandial ghrelin suppression also increased with decreasing body weight and higher CAG repeat number (both P < 0.05).


CONCLUSIONS
These findings suggest changes in the regulation of GH and ghrelin secretion dynamics in early stage HD patients that could become more prominent in the later stages of the disease.
Aziz
N A
NA
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. n.a.aziz@lumc.nl
Pijl
H
H
Frölich
M
M
Schröder-van der Elst
J P
JP
van der Bent
C
C
Roelfsema
F
F
Roos
R A C
RA
D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D016022:Case-Control Studies; D004435:Eating / Q000502:physiology; D005260:Female; D054439:Ghrelin / Q000097:blood* / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D012720:Severity of Illness Index; D013997:Time Factors; D018911:Trinucleotide Repeats
C515349:GHRL protein, human; D054439:Ghrelin; C086055:HTT protein, human; D000071058:Huntingtin Protein; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I