Thyroid dysfunction associated with increased low-density lipoprotein cholesterol in epileptic children treated with carbamazepine monotherapy: A causal relationship?

Attilakos, Achilleas; Garoufi, Anastasia; Voudris, Konstantinos; Mastroyianni, Sotiria; Fotinou, Aspasia; Papadimitriou, Dimitrios T; Gavalakis, Nikolaos; Prassouli, Alexia; Katsarou, Eustathia

doi:10.1016/j.ejpn.2007.03.002

Cited by 20 publications

(17 citation statements)

References 21 publications

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“…Most of the patients with epilepsy require a long-term, and sometimes lifelong, therapy with antiepileptic drugs (AEDs) and, therefore, are exposed to the potential undesirable metabolic side effects of medical treatment [39][40][41]. These include alterations in the metabolism of homocysteine [5,37], lipoproteins [4,19,61,62,72] and vitamin D [7,16,18,46,50]. Given the fact that an adequate vitamin D status is of major importance for multiple health outcomes [9,26,70], the effects of AEDs on the vitamin D metabolism in children is of considerable interest.…”

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confidence: 99%

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

et al. 2008

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Reports of decreased serum 25-hydroxyvitamin D (25-OHD) and altered bone metabolism associated with antiepileptic drug (AED) treatment are inconsistent and predominantly restricted to adults. In this cross-sectional observational study, the aim was to evaluate the influence of AED treatment on vitamin D status and markers of bone turnover in children with epilepsy. In 38 children taking AEDs and 44 healthy control subjects, blood samples were collected to determine the levels of serum 25-OHD, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), bone alkaline phosphatase (BAP), osteocalcin (OC) and C terminal telopeptide of type I collagen (ICTP). More than 75% of the patients were vitamin D deficient (serum 25-OHD<20 ng/mL) and 21% of the patients had an insufficient vitamin D status (serum 25-OHD=20-30 ng/mL). In the patients, the serum levels of OC (p = 0.002) and BAP (p < 0.001) were significantly increased, but ICTP (p = 0.002) concentrations were significantly decreased compared with the control group. When patients where divided into two groups according to their medication (mono- or polytherapy), significantly lower 25-OHD (p = 0.038) and ICTP (p = 0.005) levels and elevated BAP (p = 0.023) concentrations were found in patients under polytherapy. An association between 25-OHD and the measured bone markers could not be determined. Our results indicate that the prevalence of vitamin D deficiency in epilepsy patients under AED treatment is high, especially under polytherapy, and alteration markers of bone formation and resorption suggests an accelerated skeletal turnover. The routine monitoring of serum 25-OHD and vitamin D supplementation on an individual basis should be considered.

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confidence: 99%

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

et al. 2008

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“…They reported that during a 12-months period of therapy, all AEDs except levetiracetam increased TSH level and decreased fT4 concentration [142]. In another study, it was reported that carbamazepine monotherapy in epileptic children and adult patients impaired thyroid function [143]. Evidences are also available showing that AEDs affect the cellular mechanism of TH functions.…”

Section: Antiepileptic Drugs and Thyroid Hormonesmentioning

confidence: 96%

Thyroid hormones: Possible roles in epilepsy pathology

Tamijani

Karimi

Amini

et al. 2015

Seizure

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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.

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“…Antipyrine clearance (measure of the induction of cytochrome P450/monooxygenases): Seven publications (Ohnhaus et al 1981;Ohnhaus and Studer 1983;Connell et al 1984;Perucca et al 1984;Patsalos et al 1990;Larkin et al 1991;Isoj€ arvi et al 1995); Urinary excretion of D-glucaric acid or 6-b-hydroxy cortisol (indirect markers of cytochrome P450 induction): Four publications (Ohnhaus et al 1981;Ohnhaus and Studer 1983;Perucca et al 1984;Larkin et al 1991); Gamma glutamyl transferase: Four publications (Luoma et al 1980;Ohnhaus et al 1981;Ohnhaus and Studer 1983;Isoj€ arvi et al 2001); Serum lipid profiles: Two publications (Attilakos et al 2007;Elger et al 2016); Serum bilirubin: Luoma et al (1980); Thyroxine binding globulin: Ohnhaus et al (1981); Thyroxine binding globulin and transthyretin: Larsen et al (1970).…”

Section: Evidence From the Observational Studiesmentioning

confidence: 99%

Toward a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part I: which parameters from human studies are most relevant for toxicological assessments?

Sauer¹,

Asiimwe

Botham

et al. 2020

Critical Reviews in Toxicology

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Thyroid dysfunction associated with increased low-density lipoprotein cholesterol in epileptic children treated with carbamazepine monotherapy: A causal relationship?

Cited by 20 publications

References 21 publications

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy

Thyroid hormones: Possible roles in epilepsy pathology

Toward a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part I: which parameters from human studies are most relevant for toxicological assessments?

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