title: Autonomic nervous system function in chronic exogenous subclinical thyrotoxicosis and the effect of restoring euthyroidism.
abstract: BACKGROUND
  Knowledge on the relationship between the autonomic nervous system and subclinical hyperthyroidism is mainly based upon cross-sectional studies in heterogeneous patient populations, and the effect of restoration to euthyroidism in subclinical hyperthyroidism has not been studied.
  
  
  OBJECTIVE
  We investigated the long-term effects of exogenous subclinical hyperthyroidism on the autonomic nervous system and the potential effects of restoration of euthyroidism.
  
  
  METHODS
  This was a prospective single-blinded, placebo-controlled, randomized trial.
  
  
  METHODS
  The study was performed at a university hospital.
  
  
  METHODS
  A total of 25 patients who were on more than 10-yr TSH suppressive therapy after thyroidectomy was examined.
  
  
  METHODS
  Patients were studied at baseline and subsequently randomized to a 6-month thyroid hormone substitution regimen to obtain either euthyroidism or maintenance of the subclinical hyperthyroid state.
  
  
  METHODS
  Urinary excretion of catecholamines and heart rate variability were measured. Baseline data of the subclinical hyperthyroidism patients were compared with data obtained in patients with hyperthyroidism and controls.
  
  
  RESULTS
  Urinary excretion of norepinephrine and vanillylmandelic acid was higher in the subclinical hyperthyroidism patients compared with controls and lower compared with patients with overt hyperthyroidism. Heart rate variability was lower in patients with hyperthyroidism, intermediate in subclinical hyperthyroidism patients, and highest in the healthy controls. No differences were observed after restoration of euthyroidism.
  
  
  CONCLUSIONS
  Long-term exogenous subclinical hyperthyroidism has effects on the autonomic nervous system measured by heart rate variability and urinary catecholamine excretion. No differences were observed after restoration to euthyroidism. This may indicate the occurrence of irreversible changes or adaptation during long-term exposure to excess thyroid hormone that is not remedied by 6-month euthyroidism.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carmen F A
authors.initials: CF
authors.lastname: Eustatia-Rutten
authors.forename: Eleonora P M
authors.initials: EP
authors.lastname: Corssmit
authors.forename: Karen A
authors.initials: KA
authors.lastname: Heemstra
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Rik C
authors.initials: RC
authors.lastname: Schoemaker
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002395:Catecholamines / Q000652:urine; D002908:Chronic Disease; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013971:Thyrotoxicosis / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D002395:Catecholamines; D013972:Thyrotropin; D013974:Thyroxine