Altered thyrotropic and lactotropic axes regulation in Huntington's disease.
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.


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: 1.13 ± 0.14 vs 0.91 ± 0.19 mU/l, P = 0.40; prolactin: 213 ± 18 vs 209 ± 11 pmol/l, P = 0.87). However, in patients with HD, total T(3) levels were significantly higher (1.60 ± 0.05 vs 1.35 ± 0.09, P = 0.045), while T(4) levels tended to be higher as well (91.9 ± 3.9 vs 81.3 ± 3.1, P = 0.085). Prolactin secretion was significantly more irregular in patients with HD (Approximate entropy (ApEn): 1.06 ± 0.08 vs 0.80 ± 0.09, P = 0.037). Total T(3) levels were negatively associated with motor impairment (r = -0.72, P = 0.030), whereas increasing free T(4) levels were associated with a larger mutant cytosine-adenine-guanine (CAG) repeat size (r = +0.68, P = 0.044).


CONCLUSIONS
Our findings indicate a mild hyperactivity of the thyrotropic axis and a disturbed regulation of the lactotropic axis in patients with early-stage HD.
Aziz
N A
NA
Departments of Neurology Endocrinology and Metabolic Diseases Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands. N.A.Aziz@lumc.nl
Pijl
Hanno
H
Frölich
Marijke
M
Roelfsema
Ferdinand
F
Roos
Raymund A C
RA
D000328:Adult; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D013963:Thyroid Hormones; D011388:Prolactin; D013972:Thyrotropin