Altered thyrotropic and lactotropic axes regulation in Huntington’s disease

Background Recently, a loss of hypothalamic dopamine D₂ receptors was demonstrated in Huntington’s disease (HD). Activation of dopamine D₂ 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: 1·13 ±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 T₃ levels were significantly higher (1·60 ± 0·05 vs 1·35 ± 0·09, P = 0·045), while T₄ 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 T₃ levels were negatively associated with motor impairment (r = ?0·72, P = 0·030), whereas increasing free T₄ levels were associated with a larger mutant cytosine‐adenine‐guanine (CAG) repeat size (r = +0·68, P = 0·044). 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.