Document Detail

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men.
MedLine Citation:
PMID:  15625087     Owner:  NLM     Status:  MEDLINE    
Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R2 = 0.46, P = 0.02) and negatively with amount of sleep (R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.
Simon W Kok; Ferdinand Roelfsema; Sebastiaan Overeem; Gert Jan Lammers; Marijke Frölich; A Edo Meinders; Hanno Pijl
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article     Date:  2004-12-29
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  288     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-11     Completed Date:  2005-05-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E892-9     Citation Subset:  IM    
Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
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MeSH Terms
Adaptation, Physiological
Intracellular Signaling Peptides and Proteins / deficiency*
Middle Aged
Narcolepsy / blood*
Neuropeptides / deficiency*
Pituitary Gland / metabolism*
Thyroid Gland / metabolism*
Thyrotropin / blood*
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/orexins; 9002-71-5/Thyrotropin

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