Association of antiepileptic drug usage, trace elements and thyroid hormone status

Eur J Endocrinol. 2016 Apr;174(4):425-32. doi: 10.1530/EJE-15-1081. Epub 2015 Dec 23.


Background: Levels of thyroid hormone (TH) and trace elements (copper (Cu) and selenium (Se)) are important for development and function of the brain. Anti-epileptic drugs (AEDs) can influence serum TH and trace element levels. As the relationship between AEDs, THs, and trace elements has not yet been studied directly, we explored these interactions.

Method: In total 898 participants, from the Thyroid Origin of Psychomotor Retardation study designed to investigate thyroid parameters in subjects with intellectual disability (ID), had data available on serum Se, Cu, thyroid stimulating hormone (TSH), free thyroxine (FT4), tri-iodothyronine (T3), reverse T3, T4, and thyroxine-binding globulin (TBG); 401 subjects were on AED treatment. Differences in trace elements according to medication usage was investigated using ANOVA, and associations between trace elements and thyroid parameters were analysed using (non-) linear regression models.

Results: Study participants were not deficient in any of the trace elements analyzed. AED (carbamazepine, valproate and phenytoin) usage was negatively associated with serum Se and showed compound-specific associations with Cu levels. After correction for drug usage, Se was positively associated with TSH levels, negatively associated with FT4 levels, and positively with T3 levels. Cu was positively associated with T4, T3, and rT3, which was largely dependent on TBG levels.

Conclusion: The subjects with ID did not display profound deficiencies in trace element levels. AEDs were associated with serum Se and Cu levels, while serum Se and Cu were also associated with thyroid parameters. Further studies on the underlying mechanisms and potential clinical importance are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Cohort Studies
  • Copper / blood
  • Drug Interactions
  • Female
  • Humans
  • Intellectual Disability / blood
  • Intellectual Disability / complications
  • Intellectual Disability / epidemiology
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Selenium / blood
  • Thyroid Function Tests
  • Thyroid Gland / drug effects
  • Thyroid Gland / physiopathology
  • Thyroid Hormones / blood*
  • Trace Elements / blood*


  • Anticonvulsants
  • Thyroid Hormones
  • Trace Elements
  • Copper
  • Selenium