Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans:: Blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker

被引:33
作者
Kok, SW
Roelfsema, F
Overeem, S
Lammers, GJ
Strijers, RL
Frölich, M
Meinders, AE
Pijl, H
机构
[1] Leiden Univ, Med Ctr, Dept Gen Internal Med C1 R38, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Endocrinol, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands
[4] Free Univ Amsterdam Hosp, Dept Clin Neurophysiol, NL-1094 LM Amsterdam, Netherlands
关键词
D O I
10.1210/jc.2002-020638
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. It has been suggested that anomalous timing by the biological clock contributes to the symptomatology. Hypocretins stimulate the pituitary-adrenal (PA) axis in rodents. We explored whether hypocretin deficiency disrupts circadian timing and blunts PA hormone release. We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls. Basal and total ACTH production were blunted in narcoleptics [310 +/- 86 vs. 760 +/- 160 ng/liter(.)24 h (P = 0.02) and 920 +/- 147 vs. 1460 +/- 220 ng/liter(.)24 h (P = 0.04), respectively), whereas pulsatile release did not differ between groups. In contrast, basal, pulsatile and total cortisol secretion were similar in both groups. The cross-approximate en. tropy of the joint ACTH/cortisol time series was higher in narcoleptics (1.26 +/- 0.07 vs. 1.07 +/- 0.04; P = 0.04), reflecting reduced secretory process regularity. The acrophases of both ACTH and cortisol occurred at similar clock times (similar to0830 h) in patients and controls, which supports the idea that the master pacemaker is intact in narcolepsy. The reduced (basal) ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between PA hormones. (J Clin Endocrinol Metab 87: 5085-5091, 2002)
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页码:5085 / 5091
页数:7
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