Search

P>Background Recently, a loss of hypothalamic dopamine D-2 receptors was demonstrated in Huntington's disease (HD). Activation of dopamine D-2 receptors is known to inhibit the function of both thyrotropic and lactotropic axes. Objective To assess whether the activity of the thyrotropic and lactotropic axes is disturbed in patients with HD, contributing to symptoms such as unintended weight loss. Participants and methods In nine medication-free patients with early-stage HD (six men, three women) and nine age-, sex- and body mass index-matched controls, we measured serum levels of thyroid-stimulating hormone (TSH) and prolactin (men only) every 10 min for 24 h. Multiparameter auto-deconvolution and approximate entropy analysis were applied to quantify basal, pulsatile and total TSH and prolactin secretion rates as well as the regularity of hormone release. Results Compared with controls, TSH and prolactin secretion tended to be slightly, but not significantly, higher in patients with HD (TSH: 1 center dot 13 +/- 0 center dot 14 vs 0 center dot 91 +/- 0 center dot 19 mU/l, P = 0 center dot 40; prolactin: 213 +/- 18 vs 209 +/- 11 pmol/l, P = 0 center dot 87). However, in patients with HD, total T-3 levels were significantly higher (1 center dot 60 +/- 0 center dot 05 vs 1 center dot 35 +/- 0 center dot 09, P = 0 center dot 045), while T-4 levels tended to be higher as well (91 center dot 9 +/- 3 center dot 9 vs 81 center dot 3 +/- 3 center dot 1, P = 0 center dot 085). Prolactin secretion was significantly more irregular in patients with HD (Approximate entropy (ApEn): 1 center dot 06 +/- 0 center dot 08 vs 0 center dot 80 +/- 0 center dot 09, P = 0 center dot 037). Total T-3 levels were negatively associated with motor impairment (r = -0 center dot 72, P = 0 center dot 030), whereas increasing free T-4 levels were associated with a larger mutant cytosine-adenine-guanine (CAG) repeat size (r = +0 center dot 68, P = 0 center dot 044). Conclusion: Our findings indicate a mild hyperactivity of the thyrotropic axis and a disturbed regulation of the lactotropic axis in patients with early-stage HD.

P>Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. Objective To perform a detailed analysis of adipose tissue function in HD patients as abnormal fat tissue function could contribute to the weight loss. Design, setting and participants In a clinical research laboratory, 24-h plasma concentrations of leptin, adiponectin and resistin were studied in nine early-stage, medication-free HD patients and nine age-, gender- and body mass index (BMI)-matched controls. Measurements Leptin was measured every 20 min whereas adiponectin and resistin were measured hourly. Autodeconvolution and cosinor regression were applied to quantify secretion characteristics of leptin and diurnal variations in leptin, adiponectin and resistin levels. Results Plasma levels and diurnal rhythmicity of leptin, adiponectin and resistin were not significantly different between HD patients and controls. However, although leptin production increased with higher BMI and fat mass in controls, no such relation was present in HD patients. Moreover, when corrected for fat mass, mean plasma leptin concentration as well as basal, pulsatile and total secretion rates increased with the size of the CAG repeat mutation (r = +0 center dot 72 to r = +0 center dot 80; all P < 0 center dot 05). Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients. Conclusions CAG-repeat size-dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients.

Background and purpose: 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.