Thyroid function and volume in epileptic children using carbamazepine, oxcarbazepine and valproate.
ABSTRACT The aim of the present study was to investigate the effects of carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid (VPA) on thyroid function and volume in epileptic children.
Fifty-three epileptic children (age, 3-17 years) treated with OXC (n = 10), CBZ (n = 12), or VPA (n = 31) at least for 1 year were evaluated in terms of thyroid hormones, thyroid-stimulating hormone (TSH) levels, response to thyrotropin-releasing hormone (TRH) stimulation test, and thyroid volumes.
The patients in the OXC and CBZ groups had similar total thyroxin (TT4) and free T4 (fT4) median levels that were significantly lower than those of the VPA group (P < 0.016). Total tri-iodothyrosin median levels were lower in the CBZ group compared to the VPA group (P < 0.016). Basal TSH levels and thyroid volumes were similar in all groups (P > 0.016). One child from the OXC group (10%), one from the CBZ group (%8.3), and six from the VPA group (19.3%) had hypothyroidic status according to the TRH stimulation test. No statistically significant correlations were found between thyroid gland volume and thyroid function variables and between anti-epileptic drug receiving time and thyroid function or thyroid volume, respectively, in any of the groups (P > 0.05).
Thyroid function should be evaluated periodically in children using CBZ, OXC or VPA. The children taking VPA seems to be at greater risk compared to children onr CBZ or OXC therapy. Except for the basal TSH values in the VPA group, the parameters predictive for the subclinical hypothyroid status remain to be evaluated in further studies.
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ABSTRACT: Aim. This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. Methods. Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. Results. In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). Conclusion. Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.Endocrine Research 05/2012; 37(4):163-74. · 1.03 Impact Factor
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ABSTRACT: This study aimed to investigate the risk of clinically significant hypothyroidism among all the currently available antiepileptic drugs (AED). The Taiwan National Health Insurance Research Database (NHIRD) from 2004 to 2010 was analyzed using a prescription sequence symmetry analysis, and thyroxine treatment was used as a proxy to identify a hypothyroidism event. A cohort of patients who have been treated with both AED and thyroxine was selected, and the chronological order of AED and thyroxine use constituted the basis of the prescription sequence symmetry analysis. A causal relationship was suspected if there was a significantly higher proportion of patients who initiated thyroxine after AED than those who initiated thyroxine before AED. The ratio of the two proportions was described as a sequence ratio. To benchmark the effect size of AEDs on thyroid function, amiodarone was selected as the reference indicator. A total of 1,878,189 AED users was found in the database, with 16,200 of them also used thyroxine. The adjusted sequence ratio of thyroxine use after each AED was 1.75 (99% confidence interval, 1.58-1.94) for phenytoin, 1.34 (1.20-1.49) for valproate, 1.25 (1.15-1.36) for phenobarbital, 1.21 (1.08-1.34) for carbamazepine, and 1.22 (1.03-1.46) for oxcarbazepine. The risk of hypothyroidism from phenytoin use within a shorter time frame was similar that associated with amiodarone use. No association was shown in most of the new generation AEDs. The results indicated an increased risk of hypothyroidism among patients using AEDs, especially phenytoin, valproate, phenobarbital, carbamazepine, and oxcarbazepine. The findings also provided strong grounds for further investigations on acute thyroid adverse effect induced by phenytoin. Copyright © 2013 John Wiley & Sons, Ltd.Pharmacoepidemiology and Drug Safety 08/2013; · 2.90 Impact Factor
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ABSTRACT: To evaluate prospectively the changes and possible associations in lipid and thyroid profiles in children treated with oxcarbazepine (OXC) monotherapy. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), lipoprotein (a) [Lp(a)], free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and gamma-glutamyltransferase (GGT) concentrations were measured in 23 children with epilepsy, before and at 8 and 18 months of OXC monotherapy. Total cholesterol was significantly increased at 8 months (P = 0.033), whereas LDL-C was significantly increased at 8 and 18 months (P < 0.001 and P = 0.004, respectively) of treatment. Lp(a) was significantly increased at 8 months (P = 0.042) and borderline significantly increased at 18 months (P = 0.050) of treatment. FT4 was significantly decreased at 8 and 18 months (P < 0.001 and P = 0.002, respectively), and TSH levels were significantly increased at 8 and 18 months (P = 0.002 and P = 0.001, respectively) of OXC monotherapy. GGT levels were significantly increased at 8 and 18 months (P < 0.001) of treatment. There were no significant alterations in HDL-C, TGs and FT3 levels during the study. Significant positive correlations were found between GGT and LDL-C levels at 8 (r = 0.468, P = 0.024) and 18 months (r = 0.498, P = 0.016), and between TSH and TC at 18 months (r = 0.508, P = 0.013) of treatment. OXC monotherapy may cause significant and persistent alterations in lipid and thyroid profiles in children with epilepsy. The increase in LDL-C and TC levels may be associated with liver enzymes induction and thyroid dysfunction. Further long-term prospective studies are required to confirm these findings and to determine their clinical significance.European Journal of Neurology 10/2013; · 4.16 Impact Factor