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: 1.13 ± 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). 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.
BACKGROUND: Recently, a loss of hypothalamicdopamine 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: 1.13 ± 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). 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.
Authors: Eirini Kalliolia; Edina Silajdžić; Rajasree Nambron; Seán J Costelloe; Nicholas G Martin; Nathan R Hill; Chris Frost; Hilary C Watt; Peter Hindmarsh; Maria Björkqvist; Thomas T Warner Journal: PLoS One Date: 2015-10-02 Impact factor: 3.240