Thyroid hormones: Possible roles in epilepsy pathology

Abstract

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here.

Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort

“…Conversely, for the mood stabilizer lamotrigine, FDA labeling lists hypothyroidism as rare (<1 in 1000 patients) (49), and recent reviews found little to no evidence for an effect of lamotrigine on thyroid hormones (50,51). Despite the overlapping characteristics, and shared pharmacology of BD and epilepsy (52-55), we could only find literature on carbamazepine and oxcarbazepine associated with hypothyroidism in epilepsy, a disease in which the pathogenesis may involve thyroid hormones (56). Evidence from epilepsy studies shows adverse thyroid effects from valproate (51,(57)(58)(59), carbamazepine (51,57,59), and oxcarbazepine (51,59).…”

Evaluation of the Relationship Between Thyroid Dysfunction and Menstrual Migraine in Adult Females

“…Enhanced level of thyroid hormones increased oxidative state in tissues where the metabolic rates are higher. Particularly, the fact that they increase lipid per-oxidation, decrease antioxidant enzymatic activities and decrease gamma-aminobutyric acid synthesis in the brain may be a trigger for migraine (21,22). On the other hand, inadequate thyroid function results in slower metabolism, which in turn causes the body to retain fluid and mucin glycoprotein as a result of inappropriate secretion of antidiuretic hormone and this process eventually causes vasodilatation and swelling of brain tissue, which can result in cerebral hyperactivity causing migraine (23).…”

Impact of antiepileptic drugs therapy on thyroid profile in epileptic patients of Punjab origin

“…Thyroid hormones are important for maintaining carbohydrate and lipid metabolism, cell growth and development. 6,7 Hypothyroidism even in subclinical hypothyroidism form has been associated with an increased risk of coronary heart disease. 8 The prevalence of AED induced thyroid dysfunction and the long term consequences remain uncertain mainly due to routine thyroid functions tests are not performed in the clinic.…”