Altered thyrotropic and lactotropic axes regulation in Huntington's disease

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.